{"paper_id":"0df15056-d9c3-49cd-8782-dd6f6dbf91b6","body_text":"Feasibility of Anticoagulation Using Low Molecular‑Weight Heparin During Catheter-Directed Thrombolysis for Lower Extremity Deep Venous Thrombosis | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Feasibility of Anticoagulation Using Low Molecular‑Weight Heparin During Catheter-Directed Thrombolysis for Lower Extremity Deep Venous Thrombosis Yonghui Li, Junwei Wang, Rongzhou He, Junmeng Zheng, Zhibo Chen, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-42400/v3 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 28 Jan, 2021 Read the published version in Thrombosis Journal → Version 3 posted 5 You are reading this latest preprint version Show more versions Abstract Background: The optimal anticoagulant scheme during catheter-directed thrombolysis (CDT) for deep venous thrombosis (DVT) remains unknown. This study was performed to evaluate the feasibility of anticoagulation therapy using low molecular‑weight heparin (LMWH) during CDT for DVT. Methods: The clinical data of DVT patients who underwent CDT during the past six years was retrospectively collected and reviewed. Patients were divided into therapeutic-dose anticoagulation (TPDA) and sub therapeutic-dose anticoagulation (sub-TPDA) groups according to LMWH dosage. Results: A total of 61 patients involving 61 limbs were comprised. Acute and subacute DVT were identified in 39 (63.9%) and 22 (36.1%) patients, respectively. Thrombosis involving the iliac vein was identified in 34 (55.7%) patients. Inferior vena cava filter placement was performed in 38 (62.3%) patients. Intraoperatively, adjunctive balloons, stents, and thrombectomy were provided for nine (14.8%), four (6.6%), and one (1.6%) patients, respectively. Twenty (32.8%) patients accepted TPDA therapy, while 41 (67.2%) patients were administrated with sub-TPDA therapy. Median urokinase infusion rate was 2.5 (0.83 to 5) x 10 4 U/h. Median infusion duration time was 4 (2 to 14) days, and median urokinase dose infused was 2.4 (0.6 to 10.80) x 10 6 U. During CDT, five (8.2%) cases of minor bleeding were observed, and blood transfusion was not required. No major bleeding, symptomatic pulmonary embolisms, or death occurred. Complete (>90%) and partial thrombolysis (50~90%) were achieved in 56 (91.8%) patients. In comparison with sub-TPDA group, TPDA group exhibited no significant differences in baseline characteristics, clinical improvement, thrombolysis results, and complications. Conclusions: Anticoagulation therapy using low molecular‑weight heparin during CDT with low infusion rate for DVT is likely to be feasible and safe. Sub-therapeutic-dose anticoagulation and therapeutic-dose could be used for CDT with similar clinical outcome and bleeding complications. Hematology catheter-directed thrombolysis deep venous thrombosis low molecular-weight heparin dose of anticoagulation therapy. Introduction Deep venous thrombosis (DVT) is a common disease with an incidence of approximately 1 ~ 2 per 1000 persons per year. 1 It is one of the major causes of pulmonary embolism (PE), which led to nearly 1 60,000 deaths in American during the period from 1998 to 2018. 2 Although anticoagulation therapy has proven to be effective and safe in preventing PE and recurrence of DVT and improving patients’ quality of life, 3, 4 DVT management is still facing challenging since anticoagulation alone does not resolve the thrombus formed in the vein. Consequently, approximately 25~50% of proximal DVT patients develop post-thrombotic syndrome (PTS) because of valve incompetence and long-term venous hypertension. 5 Catheter-directed thrombolysis (CDT) has been proposed for symptomatic patients with severe DVT, particularly in the setting of phlegmasia alba dolens. 6 Numerous studies reported the clinical benefit of CDT in the treatment of symptomatic DVT. 7 Despite the increased interest in CDT, consensus opinion has not been reached regarding the optimal anticoagulant scheme during CDT, including the use of low molecular‑weight heparin (LMWH), safety and effectiveness of therapeutic-dose anticoagulation (TPDA) versus sub-therapeutic-dose anticoagulation (sub-TPDA) during CDT. 8, 9 In the past six years, anticoagulation therapy with LMWH was used during CDT at our institution. This study was performed to evaluate the feasibility of LMWH for CDT and explore the optimal anticoagulation dose of LMWH during CDT. Methods Data collection This retrospective study was approved by the Institutional Review Board and was performed in the Department of Cardiovascular Surgery at the Sun Yat-sen Memorial Hospital of Sun Yat-sen University. Patients who underwent CDT at our institution during the period from January 2014 to December 2019 were included. Informed consent was obtained from involved patients. Patients were diagnosed with DVT according to clinical features and ultrasounds. Clinical data including demographics, co-morbidities, risk factors, ultrasound reports, venography reports, operative notes, and complications were tabulated. Diagnosis DVT was diagnosed according to clinical manifestations, the level of D-dimer, and ultrasound results. Only patients with iliac or femoral vein thrombi were included. DVT patients with duration time (calculated from onset of symptoms) ranging from 14 days to one month were classified as subacute DVT. Definition of variables Efficacy outcomes included thrombolysis degree, clinical improvement, and mid-thigh and mid-crus circumferences after CDT. Thrombolytic efficacy of CDT was confirmed by color doppler ultrasound or venography. A scoring system mentioned by Mewissen et al 7 was used for evaluating thrombolytic outcome in this study. Complete thrombolysis was defined as > 90% thrombus removal, and few clots were found after the procedure. Partial thrombosis was defined as 50-90% thrombosis removal. Clinical improvement was defined as a significant decrease in pain and/or swelling of the affected extremity during hospitalization. Mid-thigh circumferences were measured 15 cm above the upper margin of the patella, while mid-crus circumferences were 10 cm below the lower margin of the tibial tuberosity. Safety outcomes comprised CDT‑related complications during hospital stays, including major and minor bleeding, symptomatic PE, and death. Major and minor bleeding were defined as described. 10 Systematic PE and intracranial hemorrhage were diagnosed with computer tomography, which was given for patients with signs of PE (anhelation, hyoxemia, etc.) or intracranial hemorrhage (unconsciousness, powerlessness). Groups CDT was performed by two surgical teams, and they provided anticoagulation treatment with different regimens of LMWH. Patients were divided into TPDA and sub-TPDA groups according to LMWH dosage. Anticoagulation therapy All patients accepted a weight-based (1 mg/kg) twice-a-day regimen of LMWH (Lovenox; Sanofi, Paris, France) before and after CDT. During CDT, for the sub-TPDA group, LMWH were given at a fixed-dose of 40 mg every 12 h, while the TPDA group was administered the same weight-based (1 mg/kg) twice-a-day regimen. Catheter-directed thrombolysis A recyclable inferior vena cava filter (OptEase (Cordis, USA) or Celect (Cook, USA)) was generally recommended for patients with high risk of PE: (1). previous PE; (2) planning to accept pneumatic compression treatment. The filter was implanted via the healthy femoral or jugular vein before CDT, and it was removed when the CDT ended. Retrograde catheterization of the femoral vein in the healthy lower extremity or antegrade catheterization of the popliteal vein in the affected lower extremity was performed. A 4F or 5F multi-sidehole infusion catheter (UniFuse, (Angiodynamics, USA)) was advanced. The tip of the infusion catheter was placed within the thrombus, and its position changed according to ultrasound or venography. The length of the lateral‑hole segment for placement into the thrombus was selected based on thrombus distribution. Dose of urokinase (Livzon Pharmaceutical Group, Inc., China) was calculated according to weights of patients. Urokinase was first injected at a bolus dose of 2~3 x 10 5 U. Then urokinase was continuously infused with a dose of 1~1.5 x 10 4 U/kg/d. In other words, the urokinase was given with a dose of 4~12 x 10 5 U per day (the weight ranged from 40 to 80kg). 11 In rare cases with high risks of bleeding, the estimated dose might be reduced by half. 12 The risks of bleeding were evaluated based on the guideline developed by American College of Chest Physicians 13 . Coagulation function was tested daily. Infusion rate of urokinase dosage was adjusted according to Fibrinogen (FIB) concentration: infusion rate slowed by 50% if plasma FIB concentration decreased to <1.5 g/L; CDT was suspended and restarted with a rate slowed down by 50% if plasma FIB concentration dropped to <1.0 g/L. Residual thrombus was evaluated daily with ultrasound or venography. For patients who experienced complete thrombolysis, CDT was discontinued. For patients who experienced partial thrombolysis, CDT was discontinued if patients met at least one criterion: (1). serum level of D-dimer exhibited no significant change; (2). complications with bleeding; (3). ultrasound or venography indicated no improvement. During, the catheter position might be adjusted according to thrombolytic outcome. Generally, thrombolytic duration time should be less than seven days. Adjunctive balloons and stents were used for cases with iliac vein compression or residua stenosis after CDT. During CDT, patients were put on bedrest. The affected limb was elevated and extracts of horse chestnut seeds’ tablets (Aescuven forte, CesraArzneimittelGmbll&CoKG, Germany) were used to alleviate swelling. Pneumatic compression treatment was conserved for patients who accepted ICF implantation during CDT. Elastic compression stockings were given for patients after CDT. Management of bleeding If patients manifested a major bleeding event, CDT was discontinued. FIB, prothrombin complex, or fresh frozen plasma was given. Proton-pump inhibitors were administrated for patients who experienced a gastrointestinal bleeding event. If patients had a minor bleeding event, CDT was suspended and resumed at a reduced dosage if the minor bleeding could be controlled. If the minor bleeding continued, CDT was discontinued permanently. Statistical analysis The continuous variables were expressed as the mean (standard deviation) or median (range), whereas the categorical variables were recorded as the number and percentage. A P value < 0.05 indicated a significant difference. Continuous data was analyzed with analysis of variance, paired t tests or Mann-Whitney testing, and categoric variables with Chi-square test or Fisher’s exact probabilities. Results A total of 61 patients containing 61 limbs were treated. The average age was 56.2 years old, ranging from 21 to 88. Thirty male patients and 31 females were involved. Nine patients were addicted to smoking. Thirteen patients had a history of hypertension, and five patients were diagnosed with diabetes. Clinical characteristics are shown in Table 1. Twenty-two (36.1%) patients were classified as subacute DVT. Surgery within the past 30 days was the leading cause of DVT. Risk factors of 22 patients were unknown. Thrombosis involved iliac vein was identified in 34 (55.7%) patients. The remaining 27 patients had femoropopliteal venous thrombosis. Co-existing PE was found in four (6.6%) patients. Preoperative inferior vena cava filter placement was placed in 38 (62.3%) patients. Intraoperatively, adjunctive balloons (Mustang, Boston Scientific, American), stents (Wallstent, Boston Scientific, American), and percutanous mechanical thrombectomy (AnjioJet, Boston Scientific, American) were provided for nine (14.8%), four (6.6%), and one (1.6%) patients, respectively. Twenty (32.8%) patients accepted TPDA therapy, while 41(67.2%) patients were administrated sub-TPDA therapy. Median urokinase infusion rate was 2.5 (0.83 to 5) x 10 4 U/h. Median infusion duration time was 4 (ranged 2 to 14) days, and median dose infusion was 2.4 (0.6 to 10.80) x 10 6 U. Among these, 3 patients accepted thrombolytic treatment with the dose of urakinase reduced by half because of recent surgery or active bleeding: two cases of minimally invasive surgery and one renal hemorrhage that had been managed with selective arterial embolization of renal artery. During thrombolytic therapy, five (8.2%) cases of minor bleeding were identified, and no blood transfusion was required. No major bleeding, symptomatic PE, intracranial hemorrhage, or deaths occurred. Five patients experienced a minor bleeding. Among these, four female patients and one male patient were involved, with a median age of 64 (46 to 80) years. Median thrombotic duration time was seven (four to 12) days. Median infusion rates were 3.75 (2.5 to 4.2) x 10 4 U/h, and median urokinase dosage was 4. (1.8 to 9.9) x 10 6 U. Compared with patients without bleeding, patients who experienced bleeding were given more urokinase (P= .029), and the urokinase was infused at faster rate (P= .007). The cases with bleeding were managed by slowing down the infusion rate and suspending CDT. Intervention strategies are described in Table 2. As for coagulation function, a plasma FIB concentration < 2.0g/L was found in eight patients. FIB concentration<1.5g/L was identified in two of these patients. The infusion rate of urokinase was slowed down in these two patients. No FIB was infused. After CDT, complete and partial thrombolysis was achieved in 56 (91.8%) patients, including all patients with acute DVT and 17 (77.3%) patients with subacute DVT. Patients with less than 50% thrombosis removal were all classified as subacute DVT. Among these, median urokinase dosage was 1.8 (1.6 to 6) x 10 6 U. The mid-thigh (45.8 ± 4.9 vs. 43.6 ± 4.5, P< .01) and mid-crus (36.9 ±3.4 vs. 33.9± 2.5, P< .01) circumference (cm) significantly decreased after CDT. Clinical improvement was confirmed in 57 (93.4%) patients. Clinical outcome is shown in Table 3. In comparison with sub-TPDA group, TPDA group did not exhibit significant difference in demographic characteristics, lesion characteristics, use of urokinase, and adjunctive strategies. Mid-thigh and mid-crus circumference, clinical improvement, rate of complete and partial thrombolysis, and bleeding were similar between the two groups. Comparison of outcomes are described in detail in Table 4. Discussion Although various strategies were applied for removing thrombus, CDT remained the mainstream therapeutic strategy. CDT therapy could not only reduce mechanical trauma to the vessel wall compared with an open balloon thrombectomy procedure, but also manage thrombus in smaller distal vessels that are generally not accessible by a thrombectomy catheter. 14 In clinical practice, CDT therapy was increasingly used in combination with percutaneous mechanical thrombectomy, creating a pharmacomechanical thrombectomy system. Unfractionated heparin was preferentially used for anticoagulation therapy during CDT due to its shorter half-life and complete reversibility by using protamine. Though favorable results have been obtained, numerous studies have demonstrated that risks of bleeding related to CDT therapy were alarmingly high, particularly in elderly patients. 7, 15, 16 In comparison with unfractionated heparin, LMWH seemed to be equally effective and safer for venous thromboembolism. 17 In addition, unfractionated heparin was given by intravenous continuous infusion during CDT, while LMWH was easier to use by subcutaneous injection. However, the evidence of using of LMWH during CDT was limited. In Chen et al 12 study involving 46 patients with acute iliofemoral venous thrombosis, LMWH in combination with low dose urokinase was applied for CDT. Patients were divided into high-risk and low-risk groups according to their risk of bleeding. The high-risk group received CDT with a median infusion rate of 1.0 x 10 4 U/h, while the low-risk group had a median infusion rate of 2.0 x 10 4 U/h. The rate of complete thrombolysis and clinical improvement was consistent with studies using unfractionated heparin for CDT, 18 and the rate of bleeding was lower. A retrospective study performed by Graif et al 19 included 45 patients accepting anticoagulation with LMWH during CDT for PE and 111 patients with unfractionated heparin. Graif et al 19 found that therapeutic anticoagulation using LMWH during CDT for PE was safe. Their study did not find a significant difference between LMWH and unfractionated heparin with respect to hemorrhagic and general complication rates. Favorable results were observed in the present study as well. Clinical improvement was achieved in all patients with acute DVT. The rate is acceptable in comparison with other studies. 16 For patients with subacute DVT, who were thought to be poorly responsive to CDT, 20 complete or partial thrombolysis was also identified in nearly 75% of cases. In addition, a relatively low rate of adjunctive strategies, including balloons, stents, and percutanous mechanical thrombectomy, was applied, which might underestimate the thrombolytic result. 21, 22 In a meta-analysis involving 45 studies, major bleeding occurred in 196 (7.9%) of 2467 patients experiencing CDT, and 18 (0.8%) of 2388 patients underwent CDT developed intracranial bleeding. 23 No major bleeding or intracranial bleeding was identified in the present study. Minor bleeding occurred in 8.2% of patients. The rate of minor bleeding was lower compared with studies in which unfractionated heparin was used for anticoagulation therapy, 22 which could be explained by relatively low infusion rate of urokinase. On coagulation function assay, FIB concentration < 1.5g/L was identified in two patients, and it was reversible by suspending CDT. These results indicated that it is safer to use LMWH for CDT. We respectively reviewed the infusion rate, urokinase dosage, and thrombolytic duration of patients who underwent minor bleeding. Patients with bleeding were found to have faster infusion rate and more urokinase. The results showed that the risks of bleeding increased as dosage and infusion rate increased. Based on our results, it is reasonable that thrombolytic duration time should not exceed seven days and total dose of urokinase should be less than 4 x 10 6 U. Furthermore, given the infusion rate was relatively low in the present cohort, the conclusions should be carefully quoted and might be confined to CDT with low infusion rate. The optimal dose of anticoagulation remained unclear during CDT. In comparison with sub-TPDA group, CDT with TPDA exhibited no significant difference in thrombolytic outcome or bleeding complications in the present study. The similar results could be explained as follows. Dose of urokinase and infusion rate had a higher impact on the clinical outcome, and the effect of anticoagulation therapy might be overshadowed. The relatively limited number of patients involved might affect the power of statistical tests. Based on these results, both sub-therapeutic and therapeutic dose LMWH could be used for anticoagulation therapy during CDT. Serial hematocrit levels and coagulation function assays should be mandatory, 24,25 and they were performed daily in the present study. The frequency of testing was less than that accepting anticoagulation therapy with unfractionated heparin. 26 We observed that parameters of blood coagulation were stable during CDT. Anti-factor Xa level could be used for monitoring of LWMH. However, the optimal anti-factor Xa level was unknown during CDT. 24, 26 The assay was not available at that time in our center. Further studies evaluating optimal anti-factor Xa level during CDT should be performed. Limitations First, the present study was based on retrospectively collected data and shared the same flaws as other observational studies. Second, follow-up outcome variables were absent in the present study. Outcome variables should be broadened to include follow-up outcome variables that were related with CDT, such as PTS and quality of life. Furthermore, regimen of CDT varied among patients, which might influence the reliability of conclusions. Conclusions Anticoagulation therapy using low molecular‑weight heparin during CDT with low infusion rate for DVT is likely to be feasible and safe. Sub-therapeutic-dose anticoagulation and therapeutic-dose could be used for CDT with similar clinical outcome and bleeding complications. Declarations Ethics, approval and consent to participate: This retrospective study was approved by the Institutional Review Board and was performed in the Department of Cardiovascular Surgery, the Sun Yat-sen Memorial Hospital of Sun Yat-sen University. Consent for publication : Not applicable. Availability of data and materials: The datasets used during the current study are available from the corresponding author on reasonable request. Competing interests: None. Funding: This study was partially supported by grants from the Sun Yat-sen Clinical Research Cultivating Program (Grant No. SYS-Q-202003). Authors' contributions: Yonghui Li and Junwei Wang: (1) the conception and design of the study, acquisition of data, analysis, and interpretation of data, (2) drafting the article and revising it for important intellectual content, (3) final approval of the version to be submitted. Rongzhou He: (1) acquisition of data, analysis, and interpretation of data, (2) article revision, (3) final approval of the version to be submitted. Junmeng Zheng: (1) acquisition and analysis of data, (2) article revision, (3) final approval of the version to be submitted. Zhibo Chen: (1) acquisition of data, (2) article revision, (3) final approval of the version to be submitted. Chen Yao and Kai Huang: (1) the conception and design of the study, acquisition of data, analysis and interpretation of data, (2) revising it for important intellectual content, (3) final approval of the version to be submitted and funding. Acknowledgements: This study was partially supported by grants from the Sun Yat-sen Clinical Research Cultivating Program (Grant No. SYS-Q-202003). References Kearon C, Akl EA. Duration of anticoagulant therapy for deep vein thrombosis and pulmonary embolism. Blood. 2014;123(12):1794-801. Karlyn A Martin, Rebecca Molsberry, Michael J Cuttica, Kush R Desai, Daniel R Schimmel, Sadiya S Khan，Time Trends in Pulmonary Embolism Mortality Rates in the United States, 1999 to 2018, J Am Heart Assoc. 2020;9(17):e016784. Kearon C, Akl EA, Ornelas J, Blaivas A, Jimenez D, Bounameaux H, et al. 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Tables Table 1. Clinical characteristics of 61 cases of DVT patients experiencing catheter-directed thrombosis. Variables No.(%) or median (range) Patents, n 61 Age, year 56.2 (21 to 88) Female 31 (50.8) Weight, kg 61.5 (43 to 82) Smoking 9 (14.8) Symptom duration Acute (0-2w) 39 (63.9) Subacute (2w-1m) 22 (36.1) Risk factors Surgery within last 30 days 10 (16.4) Immobilization 7 (11.5) Malignancy 8 (13.1) Childbirth 1 (1.6) Trauma 5 (8.2) Oral contraceptive use 1 (1.6) Previous DVT or PE 3 (4.9) Hypercoagulable state 2 (3.3) Cockett sydrome 2 (3.3) Unknown 22 (36.1) Involving iliac vein 34 (55.7) Co-existing PE 4 (6.6) Pre-operative mid-thigh circumference, cm 45.8 (4.9) a Pre-operative mid-crus circumference, cm 36.9 ( 3.4) b Note: w=week, m=month, DVT= deep venous thrombosis, PE= pulmonary embolism, a 10 cm from lower margin of the tibial tuberosity; b 15 cm from upper margin of the patella. Table 2. Intervention strategies of 61 cases of catheter-directed thrombosis Variables No.(%) or median (range) Balloon 9 (14.8) Stent 4 (6.6) Percutanous mechanical thrombectomy 1 (1.6) Inferior vena cava filter placement 38 (62.3) Aspiration using catheter 2 (3.3) Low molecular heparin Therapeutic dose 23 (37.7) Subtherapeutic dose 38 (62.3) Median urokinase dose, 10,000U 240 (60 to 1080) Median infusion rates, 10,000 U/hour 2.5 (0.8 to 5) Median duration time, day 4 (2 to 14) Table 3. Clinical outcome of 61 cases of DVT patients underwent catheter-directed thrombolysis. Variables No.(%) or mean (standard deviation) Thrombolysis degree Complete 13 (21.3) Partial 43 (70.5) Clinical improvement 57 (93.4) Post-eroperative mid-thigh circumference 43.6 (4.5) a Post-eroperative mid-crus circumference 33.9 (2.5) b Complications Bleeding 5 (8.2) Minor bleeding 5 (8.2) Errhysis at the puncture site 1 (1.6) Dermal ecchymosis 2 (3.3) Menorrhagia 2 (3.3) Major bleeding 0 (0) PRBC transfusion 0 (0) Death 0 (0) Allergy 1 (1.6) Note: a 10 cm from lower margin of the tibial tuberosity; b 15 cm from upper margin of the patella. PRBC= packed red blood cells Table 4. Comparison outcome of therapeutic dose group and sub-therapeutic dose group. Variable TPDA group sub-TPDA group P value Number 23 38 - Female 9 (39.1) 22 (57.9) 0.155 Age 57.4 (17.3) 54.3 (13.7) 0.466 Acute DVT 15 (65.2) 24 (63.2) 0.871 Subacute DVT 8 (34.8) 14 (36.8) Thrombolytic treatment Median infusion rates 10,000U/hour 2.5 (0.8-4.2) 2.5 (1.7-5) 0.891 Median dose, 10,000U 240 (60-1080) 240 (80-480) 0.456 Median duration time, day 4 (2-12) 4 (2-14) 0.131 Balloon 3 (13.0) 3 (7.9) 1.000 Stent 1 (4.3) 6 (15.8) 0.236 Thrombosis degree Undissolved 3 (13.0) 2 (5.3) 0.665 Partial 15 (65.2) 28 (73.7) Complete 5 (21.7) 8 (21.1) Clinical improvement 20 (87.0) 37 (97.4) 0.146 Decreased mid-thigh circumference, cm 2.1 (2.4) 2.4 (1.8) 0.716 a Decreased mid-crus circumference, cm 2.2 (1.9) 3.1 (2.2) 0.268 b Bleeding Major bleeding 0 (0) 0 (0) 1.000 Minor bleeding 1 (4.3) 4 (10.5) 0.641 Note: w=week, m=month, DVT= deep venous thrombosis, a 10 cm from lower margin of the tibial tuberosity; b 15 cm from upper margin of the patella. Cite Share Download PDF Status: Published Journal Publication published 28 Jan, 2021 Read the published version in Thrombosis Journal → Version 3 posted Editorial decision: Accept 17 Jan, 2021 Editor assigned by journal 21 Dec, 2020 Reviewers invited by journal 21 Dec, 2020 Submission checks completed at journal 21 Dec, 2020 Editor invited by journal 21 Dec, 2020 You are reading this latest preprint version Show more versions Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {\"props\":{\"pageProps\":{\"initialData\":{\"identity\":\"rs-42400\",\"acceptedTermsAndConditions\":true,\"allowDirectSubmit\":false,\"archivedVersions\":[],\"articleType\":\"Research\",\"associatedPublications\":[],\"authors\":[{\"id\":7016628,\"identity\":\"2e9bd5a2-7a6f-48c0-81d0-aa82186b0a59\",\"order_by\":0,\"name\":\"Yonghui Li\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"the Sun Yat-sen Memorial Hospital of Sun Yat-sen University\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Yonghui\",\"middleName\":\"\",\"lastName\":\"Li\",\"suffix\":\"\"},{\"id\":7016629,\"identity\":\"6392c00f-9c1b-4d60-9e55-316b1c623527\",\"order_by\":1,\"name\":\"Junwei Wang\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Second Xiangya Hospital\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Junwei\",\"middleName\":\"\",\"lastName\":\"Wang\",\"suffix\":\"\"},{\"id\":7016630,\"identity\":\"ed936952-431c-40df-a64c-f34c910a3cd1\",\"order_by\":2,\"name\":\"Rongzhou He\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"the First Affiliated Hospital of Sun Yat-sen University\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Rongzhou\",\"middleName\":\"\",\"lastName\":\"He\",\"suffix\":\"\"},{\"id\":7016631,\"identity\":\"6a838801-784c-4ec7-90ea-9d9588112ca4\",\"order_by\":3,\"name\":\"Junmeng Zheng\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"the Sun Yat-sen Memorial Hospital of Sun Yat-sen University\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Junmeng\",\"middleName\":\"\",\"lastName\":\"Zheng\",\"suffix\":\"\"},{\"id\":7016632,\"identity\":\"9c1bfc95-fbb3-4415-9ef0-37c4e027b147\",\"order_by\":4,\"name\":\"Zhibo Chen\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Sun Yat-sen University Second Univeristy Hospital\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Zhibo\",\"middleName\":\"\",\"lastName\":\"Chen\",\"suffix\":\"\"},{\"id\":7016633,\"identity\":\"8d52386c-899c-448f-a928-6368e7979c50\",\"order_by\":5,\"name\":\"Chen Yao\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"the first affiliated hosptial of Sun Yat-Sen University\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Chen\",\"middleName\":\"\",\"lastName\":\"Yao\",\"suffix\":\"\"},{\"id\":7016634,\"identity\":\"c6ee9e01-ac08-42c1-b14e-fe310eb45012\",\"order_by\":6,\"name\":\"Kai Huang\",\"email\":\"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAtklEQVRIiWNgGAWjYNACAxs7fmbmww9I0FKQlizZzpZmQIKWD4cZN5znUZAgSrFu++GDt3kM0piND/MwGDDU2EQT1GJ2Ji3ZmsfAhs/sMO+BBwzH0nIbCGo5kGMmDbLF7DBfggFjw2EitJx/A9JymHFzM4+BBHFabuRAtGxgJl7Ls2TLOQZpyRKHgYGcQJRfzicfvPHmDzAq+w8ffvChxoawFhBAREcCMcpRtYyCUTAKRsEowAYAgD88WIAvCD8AAAAASUVORK5CYII=\",\"orcid\":\"\",\"institution\":\"\",\"correspondingAuthor\":true,\"prefix\":\"\",\"firstName\":\"Kai\",\"middleName\":\"\",\"lastName\":\"Huang\",\"suffix\":\"\"}],\"badges\":[],\"createdAt\":\"2020-07-13 19:26:53\",\"currentVersionCode\":3,\"declarations\":\"\",\"doi\":\"10.21203/rs.3.rs-42400/v3\",\"doiUrl\":\"https://doi.org/10.21203/rs.3.rs-42400/v3\",\"draftVersion\":[],\"editorialEvents\":[{\"content\":\"https://doi.org/10.1186/s12959-021-00260-3\",\"type\":\"published\",\"date\":\"2021-01-28T15:01:37+00:00\"}],\"editorialNote\":\"\",\"failedWorkflow\":false,\"files\":[{\"id\":13643722,\"identity\":\"121176fc-0486-439a-9d9e-d2f378097e31\",\"added_by\":\"auto\",\"created_at\":\"2021-09-17 09:12:20\",\"extension\":\"pdf\",\"order_by\":0,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"manuscript-pdf\",\"size\":293453,\"visible\":true,\"origin\":\"\",\"legend\":\"\",\"description\":\"\",\"filename\":\"manuscript.pdf\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-42400/v3/ee2a67df-4cd6-4854-ad29-902ca01db596.pdf\"}],\"financialInterests\":\"\",\"formattedTitle\":\"Feasibility of Anticoagulation Using Low Molecular‑Weight Heparin During Catheter-Directed Thrombolysis for Lower Extremity Deep Venous Thrombosis\",\"fulltext\":[{\"header\":\"Introduction\",\"content\":\"\\u003cp\\u003eDeep venous thrombosis (DVT) is a common disease with an incidence of approximately 1 ~ 2 per 1000 persons per year.\\u003csup\\u003e1\\u003c/sup\\u003e It is one of the major causes of pulmonary embolism (PE), which led to nearly 1 60,000 deaths in American during the period from 1998 to 2018.\\u003csup\\u003e2\\u003c/sup\\u003e\\u0026nbsp;\\u003c/p\\u003e\\n\\u003cp\\u003eAlthough anticoagulation therapy has proven to be effective and safe in preventing PE and recurrence of DVT and improving patients\\u0026rsquo; quality of life,\\u003csup\\u003e3, 4\\u003c/sup\\u003e DVT management is still facing challenging since anticoagulation alone does not resolve the thrombus formed in the vein. Consequently, approximately 25~50% of proximal DVT patients develop post-thrombotic syndrome (PTS) because of valve incompetence and long-term venous hypertension.\\u003csup\\u003e5\\u003c/sup\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eCatheter-directed thrombolysis (CDT) has been proposed for symptomatic patients with severe DVT, particularly in the setting of phlegmasia alba dolens.\\u003csup\\u003e6\\u003c/sup\\u003e Numerous studies reported the clinical benefit of CDT in the treatment of symptomatic DVT.\\u003csup\\u003e7\\u003c/sup\\u003e Despite the increased interest in CDT, consensus opinion has not been reached regarding the optimal anticoagulant scheme during CDT, including the use of low molecular‑weight heparin (LMWH), safety and effectiveness of therapeutic-dose anticoagulation (TPDA) versus sub-therapeutic-dose anticoagulation (sub-TPDA) during CDT.\\u003csup\\u003e8, 9\\u003c/sup\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eIn the past six years, anticoagulation therapy with LMWH was used during CDT at our institution. This study was performed to evaluate the feasibility of LMWH for CDT and explore the optimal anticoagulation dose of LMWH during CDT.\\u003c/p\\u003e\"},{\"header\":\"Methods\",\"content\":\"\\u003cp\\u003e\\u003cstrong\\u003eData collection \\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eThis retrospective study was approved by the Institutional Review Board and was performed in the Department of Cardiovascular Surgery at the Sun Yat-sen Memorial Hospital of Sun Yat-sen University. Patients who underwent CDT at our institution during the period from January 2014 to December 2019 were included. Informed consent was obtained from involved patients. Patients were diagnosed with DVT according to clinical features and ultrasounds. Clinical data including demographics, co-morbidities, risk factors, ultrasound reports, venography reports, operative notes, and complications were tabulated.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eDiagnosis \\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eDVT was diagnosed according to clinical manifestations, the level of D-dimer, and ultrasound results. Only patients with iliac or femoral vein thrombi were included. DVT patients with duration time (calculated from onset of symptoms) ranging from 14 days to one month were classified as subacute DVT.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eDefinition of variables \\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eEfficacy outcomes included thrombolysis degree, clinical improvement, and mid-thigh and mid-crus circumferences after CDT. Thrombolytic efficacy of CDT was confirmed by color doppler ultrasound or venography. A scoring system mentioned by Mewissen et al\\u003csup\\u003e7\\u003c/sup\\u003e was used for evaluating thrombolytic outcome in this study. Complete thrombolysis was defined as \\u0026gt; 90% thrombus removal, and few clots were found after the procedure. Partial thrombosis was defined as 50-90% thrombosis removal. Clinical improvement was defined as a significant decrease in pain and/or swelling of the affected extremity during hospitalization. Mid-thigh circumferences were measured 15 cm above the upper margin of the patella, while mid-crus circumferences were 10 cm below the lower margin of the tibial tuberosity.\\u003c/p\\u003e\\n\\u003cp\\u003eSafety outcomes comprised CDT‑related complications during hospital stays, including major and minor bleeding, symptomatic PE, and death. Major and minor bleeding were defined as described.\\u003csup\\u003e10\\u003c/sup\\u003e Systematic PE and intracranial hemorrhage were diagnosed with computer tomography, which was given for patients with signs of PE (anhelation, hyoxemia, etc.) or intracranial hemorrhage (unconsciousness, powerlessness).\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eGroups\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eCDT was performed by two surgical teams, and they provided anticoagulation treatment with different regimens of LMWH. Patients were divided into TPDA and sub-TPDA groups according to LMWH dosage.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eAnticoagulation therapy \\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eAll patients accepted a weight-based (1 mg/kg) twice-a-day regimen of LMWH (Lovenox; Sanofi, Paris, France) before and after CDT. During CDT, for the sub-TPDA group, LMWH were given at a fixed-dose of 40 mg every 12 h, while the TPDA group was administered the same weight-based (1 mg/kg) twice-a-day regimen.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eCatheter-directed thrombolysis \\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eA recyclable inferior vena cava filter (OptEase (Cordis, USA) or Celect (Cook, USA)) was generally recommended for patients with high risk of PE: (1). previous PE; (2) planning to accept pneumatic compression treatment. The filter was implanted via the healthy femoral or jugular vein before CDT, and it was removed when the CDT ended.\\u003c/p\\u003e\\n\\u003cp\\u003eRetrograde catheterization of the femoral vein in the healthy lower extremity or antegrade catheterization of the popliteal vein in the affected lower extremity was performed. A 4F or 5F multi-sidehole infusion catheter (UniFuse, (Angiodynamics, USA)) was advanced. The tip of the infusion catheter was placed within the thrombus, and its position changed according to ultrasound or venography. The length of the lateral‑hole segment for placement into the thrombus was selected based on thrombus distribution. Dose of urokinase (Livzon Pharmaceutical Group, Inc., China) was calculated according to weights of patients. Urokinase was first injected at a bolus dose of 2~3 x 10\\u003csup\\u003e5 \\u003c/sup\\u003eU. Then urokinase was continuously infused with a dose of 1~1.5 x 10\\u003csup\\u003e4 \\u003c/sup\\u003eU/kg/d. In other words, the urokinase was given with a dose of 4~12 x 10\\u003csup\\u003e5 \\u003c/sup\\u003eU per day (the weight ranged from 40 to 80kg).\\u003csup\\u003e11\\u003c/sup\\u003e In rare cases with high risks of bleeding, the estimated dose might be reduced by half.\\u003csup\\u003e12\\u0026nbsp; \\u003c/sup\\u003eThe risks of bleeding were evaluated based on the guideline developed by American College of Chest Physicians\\u003csup\\u003e13\\u003c/sup\\u003e.\\u003c/p\\u003e\\n\\u003cp\\u003eCoagulation function was tested daily. Infusion rate of urokinase dosage was adjusted according to Fibrinogen (FIB) concentration: infusion rate slowed by 50% if plasma FIB concentration decreased to \\u0026lt;1.5 g/L; CDT was suspended and restarted with a rate slowed down by 50% if plasma FIB concentration dropped to \\u0026lt;1.0 g/L.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u0026nbsp; Residual thrombus was evaluated daily with ultrasound or venography. For patients who experienced complete thrombolysis, CDT was discontinued. For patients who experienced partial thrombolysis, CDT was discontinued if patients met at least one criterion: (1). serum level of D-dimer exhibited no significant change; (2). complications with bleeding; (3). ultrasound or venography indicated no improvement. During, the catheter position might be adjusted according to thrombolytic outcome. Generally, thrombolytic duration time should be less than seven days.\\u003c/p\\u003e\\n\\u003cp\\u003eAdjunctive balloons and stents were used for cases with iliac vein compression or residua stenosis after CDT. During CDT, patients were put on bedrest. The affected limb was elevated and extracts of horse chestnut seeds\\u0026rsquo; tablets (Aescuven forte, CesraArzneimittelGmbll\\u0026amp;CoKG, Germany) were used to alleviate swelling. Pneumatic compression treatment was conserved for patients who accepted ICF implantation during CDT. Elastic compression stockings were given for patients after CDT.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eManagement of bleeding\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eIf patients manifested a major bleeding event, CDT was discontinued. FIB, prothrombin complex, or fresh frozen plasma was given. Proton-pump inhibitors were administrated for patients who experienced a gastrointestinal bleeding event. If patients had a minor bleeding event, CDT was suspended and resumed at a reduced dosage if the minor bleeding could be controlled. If the minor bleeding continued, CDT was discontinued permanently.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eStatistical analysis\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eThe continuous variables were expressed as the mean (standard deviation) or median (range), whereas the categorical variables were recorded as the number and percentage. A P value \\u0026lt; 0.05 indicated a significant difference. Continuous data was analyzed with analysis of variance, paired t tests or Mann-Whitney testing, and categoric variables with Chi-square test or Fisher\\u0026rsquo;s exact probabilities.\\u003c/p\\u003e\"},{\"header\":\"Results\",\"content\":\"\\u003cp\\u003eA total of 61 patients containing 61 limbs were treated. The average age was 56.2 years old, ranging from 21 to 88. Thirty male patients and 31 females were involved. Nine patients were addicted to smoking. Thirteen patients had a history of hypertension, and five patients were diagnosed with diabetes. Clinical characteristics are shown in Table 1.\\u003c/p\\u003e\\n\\u003cp\\u003eTwenty-two (36.1%) patients were classified as subacute DVT. Surgery within the past 30 days was the leading cause of DVT. Risk factors of 22 patients were unknown. Thrombosis involved iliac vein was identified in 34 (55.7%) patients. The remaining 27 patients had femoropopliteal venous thrombosis. Co-existing PE was found in four (6.6%) patients.\\u003c/p\\u003e\\n\\u003cp\\u003ePreoperative inferior vena cava filter placement was placed in 38 (62.3%) patients. Intraoperatively, adjunctive balloons (Mustang, Boston Scientific, American), stents (Wallstent, Boston Scientific, American), and percutanous mechanical thrombectomy (AnjioJet, Boston Scientific, American) were provided for nine (14.8%), four (6.6%), and one (1.6%) patients, respectively. Twenty (32.8%) patients accepted TPDA therapy, while 41(67.2%) patients were administrated sub-TPDA therapy. Median urokinase infusion rate was 2.5 (0.83 to 5) x 10\\u003csup\\u003e4 \\u003c/sup\\u003eU/h. Median infusion duration time was 4 (ranged 2 to 14) days, and median dose infusion was 2.4 (0.6 to 10.80) x 10\\u003csup\\u003e6 \\u003c/sup\\u003eU. Among these, 3 patients accepted thrombolytic treatment with the dose of urakinase reduced by half because of recent surgery or active bleeding: two cases of minimally invasive surgery and one renal hemorrhage that had been managed with selective arterial embolization of renal artery.\\u003c/p\\u003e\\n\\u003cp\\u003eDuring thrombolytic therapy, five (8.2%) cases of minor bleeding were identified, and no blood transfusion was required. No major bleeding, symptomatic PE, intracranial hemorrhage, or deaths occurred. Five patients experienced a minor bleeding. Among these, four female patients and one male patient were involved, with a median age of 64 (46 to 80) years. Median thrombotic duration time was seven (four to 12) days. Median infusion rates were 3.75 (2.5 to 4.2) x 10\\u003csup\\u003e4 \\u003c/sup\\u003eU/h, and median urokinase dosage was 4. (1.8 to 9.9) x 10\\u003csup\\u003e6 \\u003c/sup\\u003eU. Compared with patients without bleeding, patients who experienced bleeding were given more urokinase (P= .029), and the urokinase was infused at faster rate (P= .007). The cases with bleeding were managed by slowing down the infusion rate and suspending CDT. Intervention strategies are described in Table 2.\\u003c/p\\u003e\\n\\u003cp\\u003eAs for coagulation function, a plasma FIB concentration \\u0026lt; 2.0g/L was found in eight patients.\\u0026nbsp; FIB concentration\\u0026lt;1.5g/L was identified in two of these patients. The infusion rate of urokinase was slowed down in these two patients. No FIB was infused.\\u003c/p\\u003e\\n\\u003cp\\u003eAfter CDT, complete and partial thrombolysis was achieved in 56 (91.8%) patients, including all patients with acute DVT and 17 (77.3%) patients with subacute DVT. Patients with less than 50% thrombosis removal were all classified as subacute DVT. Among these, median urokinase dosage was 1.8 (1.6 to 6) x 10\\u003csup\\u003e6 \\u003c/sup\\u003eU. The mid-thigh (45.8 \\u0026plusmn; 4.9 vs. 43.6 \\u0026plusmn; 4.5, P\\u0026lt; .01) and mid-crus (36.9 \\u0026plusmn;3.4 vs. 33.9\\u0026plusmn; 2.5, P\\u0026lt; .01) circumference (cm) significantly decreased after CDT. Clinical improvement was confirmed in 57 (93.4%) patients. Clinical outcome is shown in Table 3.\\u003c/p\\u003e\\n\\u003cp\\u003eIn comparison with sub-TPDA group, TPDA group did not exhibit significant difference in demographic characteristics, lesion characteristics, use of urokinase, and adjunctive strategies.\\u0026nbsp; Mid-thigh and mid-crus circumference, clinical improvement, rate of complete and partial thrombolysis, and bleeding were similar between the two groups. Comparison of outcomes are described in detail in Table 4.\\u003c/p\\u003e\"},{\"header\":\"Discussion\",\"content\":\"\\u003cp\\u003eAlthough various strategies were applied for removing thrombus, CDT remained the mainstream therapeutic strategy. CDT therapy could not only reduce mechanical trauma to the vessel wall compared with an open balloon thrombectomy procedure, but also manage thrombus in smaller distal vessels that are generally not accessible by a thrombectomy catheter.\\u003csup\\u003e14\\u003c/sup\\u003e In clinical practice, CDT therapy was increasingly used in combination with percutaneous mechanical thrombectomy, creating a pharmacomechanical thrombectomy system.\\u003c/p\\u003e\\n\\u003cp\\u003eUnfractionated heparin was preferentially used for anticoagulation therapy during CDT due to its shorter half-life and complete reversibility by using protamine. Though favorable results have been obtained, numerous studies have demonstrated that risks of bleeding related to CDT therapy were alarmingly high, particularly in elderly patients. \\u003csup\\u003e7, 15, 16\\u003c/sup\\u003e In comparison with unfractionated heparin, LMWH seemed to be equally effective and safer for venous thromboembolism.\\u003csup\\u003e17\\u003c/sup\\u003e In addition, unfractionated heparin was given by intravenous continuous infusion during CDT, while LMWH was easier to use by subcutaneous injection. However, the evidence of using of LMWH during CDT was limited.\\u003c/p\\u003e\\n\\u003cp\\u003eIn Chen et al\\u003csup\\u003e12\\u003c/sup\\u003e study involving 46 patients with acute iliofemoral venous thrombosis, LMWH in combination with low dose urokinase was applied for CDT. Patients were divided into high-risk and low-risk groups according to their risk of bleeding. The high-risk group received CDT with a median infusion rate of 1.0 x 10\\u003csup\\u003e4\\u003c/sup\\u003e U/h, while the low-risk group had a median infusion rate of 2.0 x 10\\u003csup\\u003e4\\u003c/sup\\u003e U/h. The rate of complete thrombolysis and clinical improvement was consistent with studies using unfractionated heparin for CDT,\\u003csup\\u003e18\\u003c/sup\\u003e and the rate of bleeding was lower.\\u003c/p\\u003e\\n\\u003cp\\u003eA retrospective study performed by Graif et al\\u003csup\\u003e19\\u003c/sup\\u003e included 45 patients accepting anticoagulation with LMWH during CDT for PE and 111 patients with unfractionated heparin. Graif et al\\u003csup\\u003e19\\u003c/sup\\u003e found that therapeutic anticoagulation using LMWH during CDT for PE was safe. Their study did not find a significant difference between LMWH and unfractionated heparin with respect to hemorrhagic and general complication rates.\\u003c/p\\u003e\\n\\u003cp\\u003eFavorable results were observed in the present study as well. Clinical improvement was achieved in all patients with acute DVT. The rate is acceptable in comparison with other studies.\\u003csup\\u003e16 \\u003c/sup\\u003eFor patients with subacute DVT, who were thought to be poorly responsive to CDT,\\u003csup\\u003e20 \\u003c/sup\\u003ecomplete or partial thrombolysis was also identified in nearly 75% of cases. In addition, a relatively low rate of adjunctive strategies, including balloons, stents, and percutanous mechanical thrombectomy, was applied, which might underestimate the thrombolytic result.\\u003csup\\u003e21, 22\\u003c/sup\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eIn a meta-analysis involving 45 studies, major bleeding occurred in 196 (7.9%) of 2467 patients experiencing CDT, and 18 (0.8%) of 2388 patients underwent CDT developed intracranial bleeding.\\u003csup\\u003e23\\u003c/sup\\u003e No major bleeding or intracranial bleeding was identified in the present study. Minor bleeding occurred in 8.2% of patients. The rate of minor bleeding was lower compared with studies in which unfractionated heparin was used for anticoagulation therapy,\\u003csup\\u003e22\\u003c/sup\\u003e which could be explained by relatively low infusion rate of urokinase. On coagulation function assay, FIB concentration \\u0026lt; 1.5g/L was identified in two patients, and it was reversible by suspending CDT. These results indicated that it is safer to use LMWH for CDT.\\u003c/p\\u003e\\n\\u003cp\\u003eWe respectively reviewed the infusion rate, urokinase dosage, and thrombolytic duration of patients who underwent minor bleeding. Patients with bleeding were found to have faster infusion rate and more urokinase. The results showed that the risks of bleeding increased as dosage and infusion rate increased. Based on our results, it is reasonable that thrombolytic duration time should not exceed seven days and total dose of urokinase should be less than 4 x 10\\u003csup\\u003e6 \\u003c/sup\\u003eU. Furthermore, given the infusion rate was relatively low in the present cohort, the conclusions should be carefully quoted and might be confined to CDT with low infusion rate.\\u003c/p\\u003e\\n\\u003cp\\u003eThe optimal dose of anticoagulation remained unclear during CDT. In comparison with sub-TPDA group, CDT with TPDA exhibited no significant difference in thrombolytic outcome or bleeding complications in the present study. The similar results could be explained as follows. Dose of urokinase and infusion rate had a higher impact on the clinical outcome, and the effect of anticoagulation therapy might be overshadowed. The relatively limited number of patients involved might affect the power of statistical tests. Based on these results, both sub-therapeutic and therapeutic dose LMWH could be used for anticoagulation therapy during CDT.\\u003c/p\\u003e\\n\\u003cp\\u003eSerial hematocrit levels and coagulation function assays should be mandatory,\\u003csup\\u003e24,25\\u003c/sup\\u003e and they were performed daily in the present study. The frequency of testing was less than that accepting anticoagulation therapy with unfractionated heparin.\\u003csup\\u003e26\\u003c/sup\\u003e We observed that parameters of blood coagulation were stable during CDT. Anti-factor Xa level could be used for monitoring of LWMH. However, the optimal anti-factor Xa level was unknown during CDT.\\u003csup\\u003e24, 26\\u003c/sup\\u003e The assay was not available at that time in our center. Further studies evaluating optimal anti-factor Xa level during CDT should be performed.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eLimitations\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eFirst, the present study was based on retrospectively collected data and shared the same flaws as other observational studies. Second, follow-up outcome variables were absent in the present study. Outcome variables should be broadened to include follow-up outcome variables that were related with CDT, such as PTS and quality of life. Furthermore, regimen of CDT varied among patients, which might influence the reliability of conclusions.\\u003c/p\\u003e\"},{\"header\":\"Conclusions\",\"content\":\"\\u003cp\\u003eAnticoagulation therapy using low molecular‑weight heparin during CDT with low infusion rate for DVT is likely to be feasible and safe. Sub-therapeutic-dose anticoagulation and therapeutic-dose could be used for CDT with similar clinical outcome and bleeding complications.\\u003c/p\\u003e\"},{\"header\":\"Declarations\",\"content\":\"\\u003cp\\u003e\\u003cstrong\\u003eEthics, approval and consent to participate:\\u003c/strong\\u003e This retrospective study was approved by the Institutional Review Board and was performed in the Department of Cardiovascular Surgery, the Sun Yat-sen Memorial Hospital of Sun Yat-sen University.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eConsent for publication\\u003c/strong\\u003e: Not applicable.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eAvailability of data and materials:\\u003c/strong\\u003e The datasets used during the current study are available from the corresponding author on reasonable request.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eCompeting interests: \\u003c/strong\\u003eNone.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eFunding:\\u003c/strong\\u003e This study was partially supported by grants from the Sun Yat-sen Clinical Research Cultivating Program (Grant No. SYS-Q-202003).\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eAuthors' contributions:\\u003c/strong\\u003e Yonghui Li and Junwei Wang: (1) the conception and design of the study, acquisition of data, analysis, and interpretation of data, (2) drafting the article and revising it\\u0026nbsp; for important intellectual content, (3) final approval of the version to be submitted.\\u003c/p\\u003e\\n\\u003cp\\u003eRongzhou He: (1) acquisition of data, analysis, and interpretation of data, (2) article revision, (3) final approval of the version to be submitted.\\u003c/p\\u003e\\n\\u003cp\\u003eJunmeng Zheng: (1) acquisition and analysis of data, (2) article revision, (3) final approval of the version to be submitted.\\u003c/p\\u003e\\n\\u003cp\\u003eZhibo Chen: (1) acquisition of data, (2) article revision, (3) final approval of the version to be submitted.\\u003c/p\\u003e\\n\\u003cp\\u003eChen Yao and Kai Huang: (1) the conception and\\u0026nbsp; design of the study, acquisition of data, analysis and interpretation of data, (2) revising it for important intellectual content, (3) final approval of the version to be submitted and funding.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eAcknowledgements:\\u003c/strong\\u003e This study was partially supported by grants from the Sun Yat-sen Clinical Research Cultivating Program (Grant No. SYS-Q-202003).\\u003c/p\\u003e\"},{\"header\":\"References\",\"content\":\"\\u003col\\u003e\\n\\u003cli\\u003eKearon C, Akl EA. Duration of anticoagulant therapy for deep vein thrombosis and pulmonary embolism. Blood. 2014;123(12):1794-801.\\u003c/li\\u003e\\n\\u003cli\\u003eKarlyn A Martin, Rebecca Molsberry, Michael J Cuttica, Kush R Desai, Daniel R Schimmel, Sadiya S Khan，Time Trends in Pulmonary Embolism Mortality Rates in the United States, 1999 to 2018, J Am Heart Assoc. 2020;9(17):e016784.\\u003c/li\\u003e\\n\\u003cli\\u003eKearon C, Akl EA, Ornelas J, Blaivas A, Jimenez D, Bounameaux H, et al. Antithrombotic Therapy for VTE Disease: CHEST Guideline and Expert Panel Report. Chest. 2016;149(2):315-52.\\u003c/li\\u003e\\n\\u003cli\\u003eKahn SR, Julian JA, Kearon C, Gu CS, Cohen DJ, Magnuson EA, et al. Quality of life after pharmacomechanical catheter-directed thrombolysis for proximal deep venous thrombosis. J Vasc Surg Venous Lymphat Disord. 2020;8(1):8-23.e18.\\u003c/li\\u003e\\n\\u003cli\\u003eMakedonov I, Kahn SR, Galanaud JP. Prevention and Management of the Post-Thrombotic Syndrome. J Clin Med. 2020;9(4) :923.\\u003c/li\\u003e\\n\\u003cli\\u003eMeissner MH, Gloviczki P, Comerota AJ, Dalsing MC, Eklof BG, Gillespie DL, et al. Early thrombus removal strategies for acute deep venous thrombosis: clinical practice guidelines of the Society for Vascular Surgery and the American Venous Forum. J Vasc Surg. 2012;55(5):1449-62.\\u003c/li\\u003e\\n\\u003cli\\u003eMewissen MW, Seabrook GR, Meissner MH, Cynamon J, Labropoulos N, Haughton SH. Catheter-directed thrombolysis for lower extremity deep venous thrombosis: report of a national multicenter registry. Radiology. 1999;211(1):39-49.\\u003c/li\\u003e\\n\\u003cli\\u003eTodoran TM, Giri J, Barnes GD, Rosovsky RP, Chang Y, Jaff MR, et al. Treatment of submassive and massive pulmonary embolism: a clinical practice survey from the second annual meeting of the Pulmonary Embolism Response Team Consortium. J Thromb Thrombolysis. 2018;46(1):39-49.\\u003c/li\\u003e\\n\\u003cli\\u003eKimberly, Terry, Leo F Buckley, Ahmed Aldemerdash, John Fanikos, Heather Dell'Orfano, Fibrinolytic and Anticoagulation Therapy in Patients Undergoing Ultrasound-Assisted Catheter-Directed Thrombolysis for Pulmonary Embolism. Cardiovasc Hematol Disord Drug Targets. 2017;17(2):132-135.\\u003c/li\\u003e\\n\\u003cli\\u003eB\\u0026uuml;ller HR, Davidson BL, Decousus H, Gallus A, Gent M, Piovella F, et al. Subcutaneous fondaparinux versus intravenous unfractionated heparin in the initial treatment of pulmonary embolism. N Engl J Med. 2003;349(18):1695-702.\\u003c/li\\u003e\\n\\u003cli\\u003eDu XL, Kong LS, Meng QY, Qian A, Li WD, Chen H, et al, Safety and Efficacy of Low Dosage of Urokinase for Catheter-directed Thrombolysis of Deep Venous Thrombosis.Chin Med J (Engl). 2015;128(13):1787-92\\u003c/li\\u003e\\n\\u003cli\\u003eChen G, Shi W, He X, Lou W, Chen L, Gu J. Feasibility of continuous, catheter-directed thrombolysis using low-dose urokinase in combination with low molecular-weight heparin for acute iliofemoral venous thrombosis in patients at risk of bleeding. Exp Ther Med. 2017;13(2):751-758.\\u003c/li\\u003e\\n\\u003cli\\u003eClive Kearon, Elie A Akl, Anthony J Comerota, Paolo Prandoni, Henri Bounameaux, Samuel Z Goldhaber, et al. Antithrombotic therapy for VTE disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines, Chest. 2012;141(2 Suppl):e419S-e496S.\\u003c/li\\u003e\\n\\u003cli\\u003eLin PH, Zhou W, Dardik A, Mussa F, Kougias P, Hedayati N, et al. Catheter-direct thrombolysis versus pharmacomechanical thrombectomy for treatment of symptomatic lower extremity deep venous thrombosis. Am J Surg. 2006;192(6):782-8.\\u003c/li\\u003e\\n\\u003cli\\u003eEnden T, Haig Y, Kl\\u0026oslash;w NE, Slagsvold CE, Sandvik L, Ghanima W, et al. Long-term outcome after additional catheter-directed thrombolysis versus standard treatment for acute iliofemoral deep vein thrombosis (the CaVenT study): a randomised controlled trial. Lancet. 2012;379(9810):31-8.\\u003c/li\\u003e\\n\\u003cli\\u003eVedantham S, Goldhaber SZ, Julian JA, Kahn SR, Jaff MR, Cohen DJ, et al. Pharmacomechanical Catheter-Directed Thrombolysis for Deep-Vein Thrombosis. N Engl J Med. 2017;377(23):2240-52.\\u003c/li\\u003e\\n\\u003cli\\u003eRobertson L, Jones LE. Fixed dose subcutaneous low molecular weight heparins versus adjusted dose unfractionated heparin for the initial treatment of venous thromboembolism. Cochrane Database Syst Rev. 2017;2(2):Cd001100.\\u003c/li\\u003e\\n\\u003cli\\u003eManninen H, Juutilainen A, Kaukanen E, Lehto S. Catheter-directed thrombolysis of proximal lower extremity deep vein thrombosis: a prospective trial with venographic and clinical follow-up. Eur J Radiol. 2012;81(6):1197-202.\\u003c/li\\u003e\\n\\u003cli\\u003eGraif A, Kimbiris G, Grilli CJ, Agriantonis DJ, Putnam SG, Leung DA. Safety of Therapeutic Anticoagulation with Low-Molecular-Weight Heparin or Unfractionated Heparin Infusion during Catheter-Directed Thrombolysis for Acute Pulmonary Embolism. J Vasc Interv Radiol.. 2020;31(4):537-43.\\u003c/li\\u003e\\n\\u003cli\\u003eWholey MH, Maynar MA, Wholey MH, Pulido-Duque JM, Reyes R, Jarmolowski CR, et al. Comparison of thrombolytic therapy of lower-extremity acute, subacute, and chronic arterial occlusions. Cathet Cardiovasc Diagn. 1998;44(2):159-69.\\u003c/li\\u003e\\n\\u003cli\\u003eKim MS, Park HS. Factors associated with the development of post-thrombotic syndrome in patients with iliofemoral deep venous thrombosis who underwent catheter-directed thrombolysis. Phlebology. 2020;35(9):672-678.\\u003c/li\\u003e\\n\\u003cli\\u003eWang H, Qi X, Luo H, Zhang Q, Chen Y, Sun J. Catheter-directed thrombolysis through anterior tibial vein for treating acute extensive deep venous thrombosis. J Vasc Surg Venous Lymphat Disord. 2018;6(6):681-8.\\u003c/li\\u003e\\n\\u003cli\\u003eIzcovich A, Criniti JM, Popoff F, Lu L, Wu J, Ageno W, et al. Thrombolytics for venous thromboembolic events: a systematic review with meta-analysis. Blood Adv. 2020;4(7):1539-53.\\u003c/li\\u003e\\n\\u003cli\\u003eFleck D, Albadawi H, Shamoun F, Knuttinen G, Naidu S, Oklu R. Catheter-directed thrombolysis of deep vein thrombosis: literature review and practice considerations. Cardiovascular diagnosis and therapy Cardiovasc Diagn Ther. 2017;7(Suppl 3):S228-s37.\\u003c/li\\u003e\\n\\u003cli\\u003eVedantham S, Sista AK, Klein SJ, Nayak L, Razavi MK, Kalva SP, et al. Quality improvement guidelines for the treatment of lower-extremity deep vein thrombosis with use of endovascular thrombus removal. J Vasc Interv Radiol. 2014;25(9):1317-25.\\u003c/li\\u003e\\n\\u003cli\\u003eLong E, Pitfield AF, Kissoon N. Anticoagulation therapy: indications, monitoring, and complications. Pediatr Emerg Care. 2011;27(1):55-61; quiz 2-4.\\u003c/li\\u003e\\n\\u003c/ol\\u003e\"},{\"header\":\"Tables\",\"content\":\"\\u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"line-height: 150%; font-family: Calibri, sans-serif; font-size: 15px;\\\"\\u003eTable 1. Clinical characteristics of 61 cases of DVT patients experiencing catheter-directed thrombosis.\\u003c/span\\u003e\\u003c/p\\u003e\\n\\u003ctable style=\\\"width:426.1pt;border-collapse:collapse;border:none;\\\"\\u003e\\n \\u003ctbody\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 213.05pt;border-top: 1pt solid windowtext;border-left: none;border-bottom: 1pt solid windowtext;border-right: none;padding: 0in 5.4pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003eVariables\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 213.05pt;border-top: 1pt solid windowtext;border-left: none;border-bottom: 1pt solid windowtext;border-right: none;padding: 0in 5.4pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003eNo.(%) or median (range)\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 213.05pt;border: none;padding: 0in 5.4pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003ePatents, n\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 213.05pt;border: none;padding: 0in 5.4pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003e61\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 213.05pt;border: none;padding: 0in 5.4pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003eAge, year\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 213.05pt;border: none;padding: 0in 5.4pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003e56.2 (21 to 88)\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 213.05pt;border: none;padding: 0in 5.4pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003eFemale\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 213.05pt;border: none;padding: 0in 5.4pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003e31 (50.8)\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 213.05pt;border: none;padding: 0in 5.4pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003eWeight, kg\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 213.05pt;border: none;padding: 0in 5.4pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003e61.5 (43 to 82)\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 213.05pt;border: none;padding: 0in 5.4pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003eSmoking\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 213.05pt;border: none;padding: 0in 5.4pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003e9 (14.8)\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 213.05pt;border: none;padding: 0in 5.4pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003eSymptom duration\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 213.05pt;border: none;padding: 0in 5.4pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003e\\u0026nbsp;\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 213.05pt;border: none;padding: 0in 5.4pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;text-indent:10.5pt;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003eAcute (0-2w)\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 213.05pt;border: none;padding: 0in 5.4pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003e39 (63.9)\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 213.05pt;border: none;padding: 0in 5.4pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;text-indent:10.5pt;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003eSubacute (2w-1m)\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 213.05pt;border: none;padding: 0in 5.4pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003e22 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sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003e\\u0026nbsp;\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 213.05pt;border: none;padding: 0in 5.4pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;text-indent:10.5pt;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003eSurgery within last 30 days\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 213.05pt;border: none;padding: 0in 5.4pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003e10 (16.4)\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 213.05pt;border: none;padding: 0in 5.4pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;text-indent:10.5pt;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003eImmobilization\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 213.05pt;border: none;padding: 0in 5.4pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003e7 (11.5)\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 213.05pt;border: none;padding: 0in 5.4pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;text-indent:10.5pt;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003eMalignancy\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 213.05pt;border: none;padding: 0in 5.4pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003e8 (13.1)\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 213.05pt;border: none;padding: 0in 5.4pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;text-indent:10.5pt;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003eChildbirth\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n 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150%;\\\"\\u003eTrauma\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 213.05pt;border: none;padding: 0in 5.4pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003e5 (8.2)\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 213.05pt;border: none;padding: 0in 5.4pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;text-indent:10.5pt;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003eOral contraceptive use\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 213.05pt;border: none;padding: 0in 5.4pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003e1 (1.6)\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 213.05pt;border: none;padding: 0in 5.4pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;text-indent:10.5pt;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003ePrevious DVT or PE\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 213.05pt;border: none;padding: 0in 5.4pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003e3 (4.9)\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 213.05pt;border: none;padding: 0in 5.4pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;text-indent:10.5pt;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003eHypercoagulable state\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 213.05pt;border: none;padding: 0in 5.4pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003e2 (3.3)\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 213.05pt;border: none;padding: 0in 5.4pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;text-indent:10.5pt;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003eCockett sydrome\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 213.05pt;border: none;padding: 0in 5.4pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003e2 (3.3)\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 213.05pt;border: none;padding: 0in 5.4pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;text-indent:10.5pt;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003eUnknown\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 213.05pt;border: none;padding: 0in 5.4pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003e22 (36.1)\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 213.05pt;border: none;padding: 0in 5.4pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003eInvolving iliac vein\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 213.05pt;border: none;padding: 0in 5.4pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003e34 (55.7)\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 213.05pt;border: none;padding: 0in 5.4pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003eCo-existing PE\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 213.05pt;border: none;padding: 0in 5.4pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003e4 (6.6)\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 213.05pt;border: none;padding: 0in 5.4pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003ePre-operative mid-thigh circumference, cm\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 213.05pt;border: none;padding: 0in 5.4pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003e45.8 (4.9)\\u003csup\\u003ea\\u003c/sup\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 213.05pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003ePre-operative mid-crus circumference, cm\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 213.05pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003e36.9 ( 3.4)\\u003csup\\u003eb\\u003c/sup\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003c/tbody\\u003e\\n\\u003c/table\\u003e\\n\\u003cp\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cem\\u003eNote: w=week, m=month, DVT= deep venous thrombosis, PE= pulmonary embolism, \\u003csup\\u003ea\\u003c/sup\\u003e10 cm from lower margin of the tibial tuberosity;\\u003csup\\u003e\\u0026nbsp;b\\u003c/sup\\u003e15 cm from upper margin of the patella.\\u003c/em\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cbr\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n\\u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003eTable 2. Intervention strategies of 61 cases of catheter-directed thrombosis\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n\\u003ctable style=\\\"border-collapse:collapse;border:none;\\\"\\u003e\\n \\u003ctbody\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 213.05pt;border-top: 1pt solid windowtext;border-left: none;border-bottom: 1pt solid windowtext;border-right: none;padding: 0in 5.4pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003eVariables\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 213.05pt;border-top: 1pt solid windowtext;border-left: none;border-bottom: 1pt solid windowtext;border-right: none;padding: 0in 5.4pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003eNo.(%) or median (range)\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 213.05pt;border: none;padding: 0in 5.4pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003eBalloon\\u0026nbsp;\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 213.05pt;border: none;padding: 0in 5.4pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003e9 (14.8)\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 213.05pt;border: none;padding: 0in 5.4pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003eStent\\u0026nbsp;\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 213.05pt;border: none;padding: 0in 5.4pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003e4 (6.6)\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 213.05pt;border: none;padding: 0in 5.4pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003ePercutanous mechanical thrombectomy\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 213.05pt;border: none;padding: 0in 5.4pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003e1 (1.6)\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 213.05pt;border: none;padding: 0in 5.4pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003eInferior vena cava filter placement\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 213.05pt;border: none;padding: 0in 5.4pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003e38 (62.3)\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 213.05pt;border: none;padding: 0in 5.4pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003eAspiration using catheter\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 213.05pt;border: none;padding: 0in 5.4pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003e2 (3.3)\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 213.05pt;border: none;padding: 0in 5.4pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003eLow molecular heparin\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 213.05pt;border: none;padding: 0in 5.4pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003e\\u0026nbsp;\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 213.05pt;border: none;padding: 0in 5.4pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;text-indent:10.5pt;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003eTherapeutic dose\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 213.05pt;border: none;padding: 0in 5.4pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003e23 (37.7)\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 213.05pt;border: none;padding: 0in 5.4pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;text-indent:10.5pt;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003eSubtherapeutic dose\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 213.05pt;border: none;padding: 0in 5.4pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003e38 (62.3)\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 213.05pt;border: none;padding: 0in 5.4pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003eMedian urokinase dose, 10,000U\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 213.05pt;border: none;padding: 0in 5.4pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003e240 (60 to 1080)\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 213.05pt;border: none;padding: 0in 5.4pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003eMedian infusion rates, 10,000 U/hour\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 213.05pt;border: none;padding: 0in 5.4pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003e2.5 (0.8 to 5)\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 213.05pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003eMedian duration time, day\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 213.05pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003e4 (2 to 14)\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003c/tbody\\u003e\\n\\u003c/table\\u003e\\n\\u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003e\\u0026nbsp;\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n\\u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003e\\u0026nbsp;\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cbr\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n\\u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003eTable 3. Clinical outcome of 61 cases of DVT patients underwent catheter-directed thrombolysis.\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n\\u003ctable style=\\\"border-collapse:collapse;border:none;\\\"\\u003e\\n \\u003ctbody\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 213.05pt;border-top: 1pt solid windowtext;border-left: none;border-bottom: 1pt solid windowtext;border-right: none;padding: 0in 5.4pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003eVariables\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 213.05pt;border-top: 1pt solid windowtext;border-left: none;border-bottom: 1pt solid windowtext;border-right: none;padding: 0in 5.4pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003eNo.(%) or mean (standard deviation)\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 213.05pt;border: none;padding: 0in 5.4pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003eThrombolysis degree\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 213.05pt;border: none;padding: 0in 5.4pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003e\\u0026nbsp;\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 213.05pt;border: none;padding: 0in 5.4pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;text-indent:10.5pt;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003eComplete\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 213.05pt;border: none;padding: 0in 5.4pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003e13 (21.3)\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 213.05pt;border: none;padding: 0in 5.4pt;height: 3.5pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;text-indent:10.5pt;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003ePartial\\u0026nbsp;\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 213.05pt;border: none;padding: 0in 5.4pt;height: 3.5pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003e43 (70.5)\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 213.05pt;border: none;padding: 0in 5.4pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003eClinical improvement\\u0026nbsp;\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 213.05pt;border: none;padding: 0in 5.4pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003e57 (93.4)\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 213.05pt;border: none;padding: 0in 5.4pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003ePost-eroperative mid-thigh circumference\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 213.05pt;border: none;padding: 0in 5.4pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003e43.6 (4.5)\\u003csup\\u003ea\\u003c/sup\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 213.05pt;border: none;padding: 0in 5.4pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003ePost-eroperative mid-crus circumference\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 213.05pt;border: none;padding: 0in 5.4pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003e33.9 (2.5)\\u003csup\\u003eb\\u003c/sup\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 213.05pt;border: none;padding: 0in 5.4pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003eComplications\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 213.05pt;border: none;padding: 0in 5.4pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003e\\u0026nbsp;\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 213.05pt;border: none;padding: 0in 5.4pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003eBleeding\\u0026nbsp;\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 213.05pt;border: none;padding: 0in 5.4pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003e5 (8.2)\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 213.05pt;border: none;padding: 0in 5.4pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003eMinor bleeding\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 213.05pt;border: none;padding: 0in 5.4pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003e5 (8.2)\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 213.05pt;border: none;padding: 0in 5.4pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;text-indent:10.5pt;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003eErrhysis at the puncture site\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 213.05pt;border: none;padding: 0in 5.4pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003e1 (1.6)\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 213.05pt;border: none;padding: 0in 5.4pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;text-indent:10.5pt;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003eDermal ecchymosis\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 213.05pt;border: none;padding: 0in 5.4pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003e2 (3.3)\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 213.05pt;border: none;padding: 0in 5.4pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;text-indent:10.5pt;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003eMenorrhagia\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 213.05pt;border: none;padding: 0in 5.4pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003e2 (3.3)\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 213.05pt;border: none;padding: 0in 5.4pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003eMajor bleeding\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 213.05pt;border: none;padding: 0in 5.4pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003e0 (0)\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 213.05pt;border: none;padding: 0in 5.4pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003ePRBC transfusion\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 213.05pt;border: none;padding: 0in 5.4pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003e0 (0)\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 213.05pt;border: none;padding: 0in 5.4pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003eDeath\\u0026nbsp;\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 213.05pt;border: none;padding: 0in 5.4pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003e0 (0)\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 213.05pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003eAllergy\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width: 213.05pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003e1 (1.6)\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003c/tbody\\u003e\\n\\u003c/table\\u003e\\n\\u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cem\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003eNote: \\u003csup\\u003ea\\u003c/sup\\u003e10 cm from lower margin of the tibial tuberosity;\\u003csup\\u003e\\u0026nbsp;b\\u003c/sup\\u003e15 cm from upper margin of the patella. PRBC= packed red blood cells\\u003c/span\\u003e\\u003c/em\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n\\u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003e\\u0026nbsp;\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cbr\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n\\u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003eTable 4. Comparison outcome of therapeutic dose group and sub-therapeutic dose group.\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n\\u003ctable style=\\\"width:430.65pt;border-collapse:collapse;border:none;\\\"\\u003e\\n \\u003ctbody\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 133pt;border-top: 1pt solid windowtext;border-left: none;border-bottom: 1pt solid windowtext;border-right: none;padding: 0in 5.4pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003eVariable\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width:99.2pt;border-top:solid windowtext 1.0pt;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:none;padding:0in 5.4pt 0in 5.4pt;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003eTPDA group\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width:99.25pt;border-top:solid windowtext 1.0pt;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:none;padding:0in 5.4pt 0in 5.4pt;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003esub-TPDA group\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width:99.2pt;border-top:solid windowtext 1.0pt;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:none;padding:0in 5.4pt 0in 5.4pt;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003eP value\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 133pt;border: none;padding: 0in 5.4pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003eNumber\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width:99.2pt;border:none;padding:0in 5.4pt 0in 5.4pt;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003e23\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width:99.25pt;border:none;padding:0in 5.4pt 0in 5.4pt;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003e38\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width:99.2pt;border:none;padding:0in 5.4pt 0in 5.4pt;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003e-\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 133pt;border: none;padding: 0in 5.4pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003eFemale\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width:99.2pt;border:none;padding:0in 5.4pt 0in 5.4pt;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003e9 (39.1)\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width:99.25pt;border:none;padding:0in 5.4pt 0in 5.4pt;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003e22 (57.9)\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width:99.2pt;border:none;padding:0in 5.4pt 0in 5.4pt;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003e0.155\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 133pt;border: none;padding: 0in 5.4pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003eAge\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width:99.2pt;border:none;padding:0in 5.4pt 0in 5.4pt;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003e57.4 (17.3)\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width:99.25pt;border:none;padding:0in 5.4pt 0in 5.4pt;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003e54.3 (13.7)\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width:99.2pt;border:none;padding:0in 5.4pt 0in 5.4pt;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003e0.466\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 133pt;border: none;padding: 0in 5.4pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003eAcute DVT\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width:99.2pt;border:none;padding:0in 5.4pt 0in 5.4pt;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003e15 (65.2)\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width:99.25pt;border:none;padding:0in 5.4pt 0in 5.4pt;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan 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15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003e2 (5.3)\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd rowspan=\\\"3\\\" style=\\\"width:99.2pt;border:none;padding:0in 5.4pt 0in 5.4pt;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003e0.665\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 133pt;border: none;padding: 0in 5.4pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;text-indent:10.5pt;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003ePartial\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width:99.2pt;border:none;padding:0in 5.4pt 0in 5.4pt;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003e15 (65.2)\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width:99.25pt;border:none;padding:0in 5.4pt 0in 5.4pt;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003e28 (73.7)\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 133pt;border: none;padding: 0in 5.4pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;text-indent:10.5pt;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003eComplete\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width:99.2pt;border:none;padding:0in 5.4pt 0in 5.4pt;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003e5 (21.7)\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width:99.25pt;border:none;padding:0in 5.4pt 0in 5.4pt;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003e8 (21.1)\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 133pt;border: none;padding: 0in 5.4pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003eClinical improvement\\u0026nbsp;\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width:99.2pt;border:none;padding:0in 5.4pt 0in 5.4pt;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003e20 (87.0)\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width:99.25pt;border:none;padding:0in 5.4pt 0in 5.4pt;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003e37 (97.4)\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width:99.2pt;border:none;padding:0in 5.4pt 0in 5.4pt;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003e0.146\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 133pt;border: none;padding: 0in 5.4pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003eDecreased mid-thigh circumference, cm\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width:99.2pt;border:none;padding:0in 5.4pt 0in 5.4pt;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003e2.1 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150%;\\\"\\u003e0.716\\u003csup\\u003ea\\u003c/sup\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 133pt;border: none;padding: 0in 5.4pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003eDecreased mid-crus circumference, cm\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width:99.2pt;border:none;padding:0in 5.4pt 0in 5.4pt;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003e2.2 (1.9)\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width:99.25pt;border:none;padding:0in 5.4pt 0in 5.4pt;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003e3.1 (2.2)\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width:99.2pt;border:none;padding:0in 5.4pt 0in 5.4pt;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003e0.268\\u003csup\\u003eb\\u003c/sup\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 133pt;border: none;padding: 0in 5.4pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003eBleeding\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width:99.2pt;border:none;padding:0in 5.4pt 0in 5.4pt;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003e\\u0026nbsp;\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width:99.25pt;border:none;padding:0in 5.4pt 0in 5.4pt;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003e\\u0026nbsp;\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width:99.2pt;border:none;padding:0in 5.4pt 0in 5.4pt;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 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style='margin:0in;text-align:center;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003e0 (0)\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width:99.25pt;border:none;padding:0in 5.4pt 0in 5.4pt;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003e0 (0)\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width:99.2pt;border:none;padding:0in 5.4pt 0in 5.4pt;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003e1.000\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003ctr\\u003e\\n \\u003ctd style=\\\"width: 133pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;text-indent:10.5pt;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003eMinor bleeding\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width:99.2pt;border:none;border-bottom:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003e1 (4.3)\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width:99.25pt;border:none;border-bottom:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003e4 (10.5)\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003ctd style=\\\"width:99.2pt;border:none;border-bottom:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;\\\"\\u003e\\n \\u003cp style='margin:0in;text-align:center;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003e0.641\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n \\u003c/td\\u003e\\n \\u003c/tr\\u003e\\n \\u003c/tbody\\u003e\\n\\u003c/table\\u003e\\n\\u003cp style='margin:0in;text-align:left;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"font-size: 15px;\\\"\\u003e\\u003cspan style=\\\"font-family: Calibri, sans-serif;\\\"\\u003e\\u003cem\\u003e\\u003cspan style=\\\"line-height: 150%;\\\"\\u003eNote: w=week, m=month, DVT= deep venous thrombosis, \\u003csup\\u003ea\\u003c/sup\\u003e10 cm from lower margin of the tibial tuberosity;\\u003csup\\u003e\\u0026nbsp;b\\u003c/sup\\u003e15 cm from upper margin of the patella.\\u003c/span\\u003e\\u003c/em\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/p\\u003e\\n\\u003cp style='margin:0in;text-align:justify;font-size:14px;font-family:\\\"Calibri\\\",sans-serif;line-height:150%;'\\u003e\\u003cspan style=\\\"line-height: 150%; font-family: Calibri, sans-serif; font-size: 15px;\\\"\\u003e\\u0026nbsp;\\u003c/span\\u003e\\u003c/p\\u003e\"}],\"fulltextSource\":\"\",\"fullText\":\"\",\"funders\":[],\"hasAdminPriorityOnWorkflow\":false,\"hasManuscriptDocX\":true,\"hasOptedInToPreprint\":true,\"hasPassedJournalQc\":\"\",\"hasAnyPriority\":false,\"hideJournal\":false,\"highlight\":\"\",\"institution\":\"\",\"isAcceptedByJournal\":true,\"isAuthorSuppliedPdf\":false,\"isDeskRejected\":\"\",\"isHiddenFromSearch\":false,\"isInQc\":false,\"isInWorkflow\":false,\"isPdf\":false,\"isPdfUpToDate\":true,\"isWithdrawnOrRetracted\":false,\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"identity\":\"thrombosis-journal\",\"isNatureJournal\":false,\"hasQc\":true,\"allowDirectSubmit\":false,\"externalIdentity\":\"thrj\",\"sideBox\":\"Learn more about [Thrombosis Journal](http://thrombosisjournal.biomedcentral.com/)\",\"snPcode\":\"12959\",\"submissionUrl\":\"https://submission.nature.com/new-submission/12959/3\",\"title\":\"Thrombosis Journal\",\"twitterHandle\":\"@Thrombosis_J\",\"acdcEnabled\":true,\"dfaEnabled\":true,\"editorialSystem\":\"em\",\"reportingPortfolio\":\"BMC/SO AJ\",\"inReviewEnabled\":true,\"inReviewRevisionsEnabled\":true},\"keywords\":\"catheter-directed thrombolysis, deep venous thrombosis, low molecular-weight heparin, dose of anticoagulation therapy.\",\"lastPublishedDoi\":\"10.21203/rs.3.rs-42400/v3\",\"lastPublishedDoiUrl\":\"https://doi.org/10.21203/rs.3.rs-42400/v3\",\"license\":{\"name\":\"CC BY 4.0\",\"url\":\"https://creativecommons.org/licenses/by/4.0/\"},\"manuscriptAbstract\":\"\\u003cp\\u003e\\u003cstrong\\u003eBackground:\\u003c/strong\\u003e The optimal anticoagulant scheme during catheter-directed thrombolysis (CDT) for deep venous thrombosis (DVT) remains unknown. This study was performed to evaluate the feasibility of anticoagulation therapy using low molecular‑weight heparin (LMWH) during CDT for DVT.\\u003c/p\\u003e\\u003cp\\u003e\\u003cstrong\\u003eMethods:\\u003c/strong\\u003e The clinical data of DVT patients who underwent CDT during the past six years was retrospectively collected and reviewed. Patients were divided into therapeutic-dose anticoagulation (TPDA) and sub therapeutic-dose anticoagulation (sub-TPDA) groups according to LMWH dosage.\\u003c/p\\u003e\\u003cp\\u003e\\u003cstrong\\u003eResults:\\u003c/strong\\u003e A total of 61 patients involving 61 limbs were comprised. Acute and subacute DVT were identified in 39 (63.9%) and 22 (36.1%) patients, respectively. Thrombosis involving the iliac vein was identified in 34 (55.7%) patients. Inferior vena cava filter placement was performed in 38 (62.3%) patients. Intraoperatively, adjunctive balloons, stents, and thrombectomy were provided for nine (14.8%), four (6.6%), and one (1.6%) patients, respectively. Twenty (32.8%) patients accepted TPDA therapy, while 41 (67.2%) patients were administrated with sub-TPDA therapy. Median urokinase infusion rate was 2.5 (0.83 to 5) x 10\\u003csup\\u003e4 \\u003c/sup\\u003eU/h. Median infusion duration time was 4 (2 to 14) days, and median urokinase dose infused was 2.4 (0.6 to 10.80) x 10\\u003csup\\u003e6 \\u003c/sup\\u003eU. During CDT, five (8.2%) cases of minor bleeding were observed, and blood transfusion was not required. No major bleeding, symptomatic pulmonary embolisms, or death occurred. Complete (\\u0026gt;90%) and partial thrombolysis (50~90%) were achieved in 56 (91.8%) patients. In comparison with sub-TPDA group, TPDA group exhibited no significant differences in baseline characteristics, clinical improvement, thrombolysis results, and complications. \\u003c/p\\u003e\\u003cp\\u003e\\u003cstrong\\u003eConclusions:\\u003c/strong\\u003e Anticoagulation therapy using low molecular‑weight heparin during CDT with low infusion rate for DVT is likely to be feasible and safe. Sub-therapeutic-dose anticoagulation and therapeutic-dose could be used for CDT with similar clinical outcome and bleeding complications. \\u0026nbsp;\\u003c/p\\u003e\",\"manuscriptTitle\":\"Feasibility of Anticoagulation Using Low Molecular‑Weight Heparin During Catheter-Directed Thrombolysis for Lower Extremity Deep Venous Thrombosis\",\"msid\":\"\",\"msnumber\":\"\",\"nonDraftVersions\":[{\"code\":3,\"date\":\"2021-01-06 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