Half Dose Alteplase or Low Molecular Weight Heparin in Pulmonary Embolism with Intermediate-High risk: Real life Study at Tertiary Hospital

Half Dose Alteplase or Low Molecular Weight Heparin in Pulmonary Embolism with Intermediate-High risk: Real life Study at Tertiary Hospital | 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 Article Half Dose Alteplase or Low Molecular Weight Heparin in Pulmonary Embolism with Intermediate-High risk: Real life Study at Tertiary Hospital Ömer Selim UNAT, Pervin KORKMAZ, Akin CINKOOGLU, Ozge CAN, Elton SOYDAN, and 12 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3466076/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background and Aim: Using thrombolytics in intermediate-high risk pulmonary embolism (PE) patients or not is a controversial issue. This study aimed to evaluate the efficacy and complications of half-dose alteplase and low molecular weight heparin (LMWH) administration in PE patients with intermediate-high risk. Material and Methods : The patients diagnosed with intermediate-high risk PE at Ege University Medical Faculty Hospital between 01.01.2016 – 13.02.2023 were included in the study. The patients diagnosed with PE after the establishment of Ege Pulmonary Embolism Team (EGEPET) (2.10.2018) formed the prospective part with the thrombolytic group. The retrospective part-anticoagulation group- included the cases treated with LMWH before EGEPET. Two treatment groups were compared in terms of the one-month mortality and the one-year mortality as primary outcomes. Results: No difference was found regarding the age, comorbidities and vital findings between thrombolytic group and anticoagulation group. Only, the pulse value was higher in the thrombolytic group (p=0,032). After the treatment, the PaO 2 /FiO 2 ratio increased significantly, and the pulse rate decreased significantly in the thrombolytic group. Improvement was only seen in the pulse rate in the anticoagulation group. There was no major bleeding in both groups. One-month mortality in thrombolytic group was found in 4 patients (6.7%), while that was observed in 6 patients (15.8%) treated with LMWH (p=0,18). One-year mortality rates were 13.7% and 26.3% respectively (p=0,17). Conclusion: PaO 2 /FiO 2 ratio improved significantly and rapidly in patients treated with thrombolysis. Even one-month and one-year mortality rates were reduced in thrombolytic group, but this difference was not found statistically significant. Acute Right Heart Failure Anticoagulation Mortality Pulmonary Thromboembolism Thrombolytic Figures Figure 1 Figure 2 INTRODUCTION Acute Pulmonary Embolism (PE) is a disease with high mortality and requires rapid intervention. The increased pulmonary vascular resistance due to filling of pulmonary arteries with embolism, right heart ventricle failure and hemodynamic decompensation can cause death. Deaths occurred by PE ranks the 3rd among cardiovascular diseases ( 1 ). Acute PE is classified as low, intermediate, high risk in terms of mortality based on the guidelines of European Respiratory Society/European Society of Cardiology. The patients in low risk is treated with anticoagulant treatment initially whereas fibrinolytic/reperfusion therapy is preferred in high-risk patients (hemodynamically unstable patients). Intermediate risk PE group is divided into two classes which are intermediate-high risk and intermediate-low risk. Elias et al. found the frequency of intermediate-low risk PE as 56% and intermediate-high PE as 9,6%. The literature has shown that the frequency of intermediate-high risk is low, but it has high mortality rate. For this reason, the guidelines recommend that intermediate-high risk patients (patients who are hemodynamically stable but have right ventricle failure) should be investigated as a separate group ( 2 , 3 ). The study comparing Tenecteplase and Unfractionated Heparin in patients with radiological evidence of right ventricle failure (CTPA or ECO) and having cardiac injury documented by troponin elevation, has found that hemodynamic decompensation occurs less in the thrombolytic group but bleeding is detected at higher rates ( 4 ). In the meta-analysis which contains all patients with intermediate risk, Marti et al. has pointed that thrombolysis does not provide additional benefits also it increases bleeding risk compared to initial anticoagulation treatment ( 5 ). There is no statistically significant difference between the efficacy of thrombolysis and low molecular weight heparin (LMWH) in hemodynamically stable patients with right ventricle failure proven by CTAP or ECO without the evaluation of cardiac biomarkers ( 6 ). According to literature, there is no sufficient and accurate data about the treatment of intermediate-high risk PE patients. Hence, this study aimed to compare the administration of half-dose Alteplase and LMWH in intermediate-high risk PE patients by evaluating the effect of half-dose Alteplase in one-month and one-year all-cause mortality and assessing treatment complications. MATERIALS and METHODS 3.1. Study Protocol This observational, single-centered study was designed with prospective and retrospective stages. The patients diagnosed with PE at Ege University Medical Faculty Hospital between 01.01.2016–13.02.2023 and classified as intermediate-high risk group according to the 2019 ERS/ESC guidelines were included in the study. The study was approved by the Clinical Research Ethics Committee of Ege University Faculty of Medicine (22 − 4.3/26) and by Republic of Türkiye Ministry of Health, Turkish Medicines and Medical Devices Agency (21-AKD-107). 3.2. Patient Population Ege Pulmonary Embolism Team (EGEPET) was established on 2.10.2018 in Ege University Faculty of Medicine for rapid diagnosis and treatment of PE. The patients, evaluated at EGEPET between 02.10.2018 and 13.02.2023 and diagnosed with intermediate-high risk PE and treated with half dose thrombolysis, were included in the study prospectively. Prior to the establishment of EGEPET, patients who were diagnosed with intermediate-high PE between 01.1.2016–2.10.2018 and were treated with only anticoagulation were included in the study retrospectively. Inclusion Criteria : Patients aged 18 years or older, whose PE was confirmed with CTPA or V/P scintigraphy, patients classified as intermediate-high risk in terms of early mortality, and patients who received half-dose thrombolysis were included in the prospective group. The patients treated with LMWH were included in the retrospective group. The patients provided informed consent forms to participate in the study. Exclusion Criteria : The patients with missing data, the patients whose right ventricle failure could not be documented clearly, the patients having contraindication for thrombolysis, the patients who were given full-dose thrombolysis because of hemodynamic instability in the emergency department during follow-up after initial treatment, the patients who received half-dose thrombolysis and whose treatment was completed to the full dose due to clinical findings in the follow-up, the patients who were not suitable for thrombolysis administration due to the high risk of bleeding with the decision of EGEPET and the patients who had unstable comorbidities that may have effects on mortality (etc. malignancy or general medical condition) were excluded from the study. 3.3. Pulmonary Embolism Diagnosis, Mortality Status Evaluation and Bleeding Risk Scoring Pulmonary embolism was diagnosed with CTPA or V/P scintigraphy. The sPESI score was calculated with the comorbidities and vital parameters of the hemodynamically stable patients. The right ventricular failure was evaluated with CTPA or Echocardiography. Troponin was used to assess right ventricular functions. Intermediate-high risk group was defined as patients with sPESI score ≥ 1 and evidence of right ventricular failure on ECHO or BTPA and elevated troponin or patients with sPESI score 0 and right ventricular dysfunction detected by imaging methods and biomarkers. The risk classification of the patients was discussed and decided at EGEPET. The early mortality risk for the patients before the establishment of EGEPET was performed retrospectively according to ESC/ERS PE guideline ( 2 ). RIETE and HAS-BLED scores were calculated and recorded for bleeding risk. ( 7 , 8 ). 3.4. Treatment Decision and Method of Application The treatments of the patients included in the prospective group were determined by the EGEPET group, available 24/7 using the Whatsapp® application, and the treatments of the cases in the retrospective period were determined by the physicians who monitored them. As thrombolytic therapy for the introspective group, 50 mg alteplase was administered by intravenous infusion over two hours. After alteplase, the anticoagulant treatments of patients were continued by LMWH. If the kidney function test was not impaired, anticoagulation was used in the retrospective group as 2x0.100 anti-XA IU/kg (e.g., 2x6000 IU for a 60 kg patient) Enoxaparin was administered subcutaneously. 3.5. Evaluation of Complications Hemorrhagic stroke, major bleeding, minor bleeding, and heparin-associated thrombocytopenia (HIT) were evaluated as treatment complications. Major bleeding: Bleeding in critical organs (intracranial, intraocular, pericardial hemorrhage), and a decrease in hemoglobin more than 2 g/dL were considered as fatal bleeding that led to death within 7 days. Minor bleeding was also assessed as bleeding other than major bleeding that affected the clinical status of the patient albeit to a lesser extent ( 9 ). Chronic Pulmonary Thromboembolism (CPTE): The patients who received maintenance anticoagulation therapy at an effective dose for 3 months but still had evidence of PE on CTPA or V/P Scintigraphy were defined as having "Chronic Pulmonary Thromboembolism (CPTE)" ( 2 ). In case that the patients had both CPTE and right ventricle failure findings at echocardiograph, they were diagnosed with Chronic Thromboembolic Pulmonary Hypertension (CTEPH), after the exclusion of other possible pulmonary hypertension causes. Recurrent Pulmonary Thromboembolism (Re-Emboli) was defined as re-development of PE in patients with clinical relief after the diagnosis of pulmonary thromboembolism ( 9 , 10 ). Mortality was evaluated as one-month and one-year all-cause mortality after the diagnosis time of PE. 3.6. Collection and Recording of Study Data Patient data during the EGEPET period was recorded from the electronic patient file without any intervention. Information of the patients diagnosed before EGEPET was obtained retrospectively using electronic patient files or written patient files. All of the data were recorded the prepared data form. Age, gender, smoking status, comorbidities, PE risks, Charlson Comorbidity Index, admission clinical and laboratory parameters, and sPESI scores of all patients were recorded after applying inclusion and exclusion criteria. Systemic arterial blood pressure, pulse and oxygenation status on the admission day (before treatment) and second days of treatment; complications, mortality status were evaluated. 3.7. Statistics Statistical analyzes were made with SPSS (Statistical Package for Social Sciences) 20.0 program. The distributions of the variables were evaluated with the “Kolmogorov-Smirnov and Shapiro-Wilk Test”. While numerical data were presented as mean ± standard deviation or median (Iq25-Iq75) value, categorical variables were presented as “%”.The parameters that fit the normal distribution were compared by Student-t test and the parameters that did not fit the normal distribution were compared by Mann-Whitney U test, which is a nonparametric test. Chi-square or Fisher Exact test was used to compare categorical variables. The power analysis before the study had indicated that for get an effective result sample size should be 160 patients on both groups. In the prospective part of the study, we evaluated 265 patients and, in the retrospective part of the study we evaluated 366 patients. The number of patients which intermediate-high risk PE and carries inclusion and exclusion criteria was 59 and that number was 38. The comparison of the parameters evaluated on the admission and second days of the treatment was performed with the Wilcoxon test. The value of “p < 0.05” was accepted as statistically significant. RESULTS 4.1. Patient Population Prospectively, 59 patients who were diagnosed with medium-high-risk PE during the EGEPET period and received half-dose thrombolysis were included in the study as "thrombolytic group". For the "anticoagulant group", 366 patients diagnosed with PE and hospitalized in the Ege University Medical Faculty Pulmonary Diseases Service or Intensive Care Unit between January 2016 and October 2018 were screened retrospectively. Thirty-eight patients were classified as intermediate-high risk PE, meeting the criteria for this study (Figure 1). Figure 1: Identification of the patient population 4.2. Findings of Patients in the Thrombolytic Group and Anticoagulation Group 4.2.1 Patients’ Demographic and Clinical Characteristics PE diagnosis was done with CTPA in the majority of the patients (98%). Only one patient was examined with V/P scintigraphy. Another patient could not undergo CT, due to being morbidly obese, and therefore PE was diagnosed with presence of right ventricle failure on echocardiography and DVT on Doppler USG. The median age of two groups were similar, but the female ratio in thrombolytic group was higher compared to the other group (45,8% vs 68,4% and p=0.037). All patients in the thrombolytic group had bilateral PE. In the anticoagulation group, 35 patients (92.1%) had bilateral PE (p=0.59). There was no difference between the two groups regarding the comorbidities, sPESI score, RIETE and HAS-BLED bleeding scores and recurrent embolism history. The median Charlson Comorbidity Index value was 4 (2.0-5.75) in the anticoagulation group, whereas it was found as 3 (1.0-5.0) in the thrombolytic group (p=0.050). The hemoglobin and d-dimer value were found to statistically significant between the two groups (Table 1). Figure 2 presents the sPESI distribution of both groups. Table 1. Demographic and clinical characteristics of the cases in the thrombolytic group and the anticoagulation group Parameters Thrombolytic Group (n=59) Anticoagulation Group (n=38) p value Age, (year)* 66 (51,0-73,0) 68 (59,5-79,25) 0,054 Female, n (% ) 27 (45,8) 26 (68,4) 0,037 Comorbidities, n (%) Hypertension 30 (50,8) 20 (54,1) 0,84 Diabetes Mellitus 11 (18,6) 8 (21,6) 0,79 Malignancy 9 (15,3) 7 (18,4) 0,78 Dementia, CVD, Alzheimer, Parkinson 7 (11,9) 6 (15,8) 0,76 Coronary Artery Disease 6 (10,2) 4 (10,8) 1.0 CHF 1 (1,7) 2 (5,3) 0,56 Hypothyroidism 3 (5,1) 2 (5,3) 1.0 Rheumatism Disease 3 (5,1) 3 (8,1) 0,67 COPD 3 (5,1) 2 (5,3) 1.0 IPF 0 1 (2,6) 0,39 Renal Failure 1 (3,4) 1 (2,7) 1.0 Charlson Comorbidity Index* 3,0 (1,0-5,0) 4 (2,0-5,75) 0,050 sPESI score* 2,0 (1,0-2,0) 2,0 (1,0-2,0) 0,95 RIETE score* 2,0 (1,0-2,5) 2,50 (1,0-3,275) 0,10 HAS-BLED* 2,0 (1,0-2,0) 2,0 (1,0-2,0) 0,49 D-dimer (µg/L)* 4500 (4321-4572) 4281 (4249-4336) <0,001 Troponin (ng/L)* 55,0 (36,0-133,0) 62,0 (32,0-99,0) 0,36 Creatinine (mg/dL)* 1,0 (0,8-1,21) 0,92 (0,77-1,22) 0,216 Hemoglobin (g/dL), (mean±SD) 13,82±2,12 12,35±2,12 0,001 Platelet count (/µL)* 218000 (180000-275000) 236000 (194750-306750) 0,21 *: median (Iq25-Iq75) Abbreviations: CHF: Congestive Heart Failure, COPD: Chronic Obstructive Pulmonary Disease, CTPA: Computed Thorax Pulmonary Angiography, CVD: Cerebrovascular Disease, IPF: Idiopathic Pulmonary Fibrosis, , SD: Standard Deviation, , sPESI: Simplified Pulmonary Embolism Severity Index. Figure 2. The distribution of sPESI scores of the cases in the thrombolytic and anticoagulation groups The comparison of the two groups regarding the PE risk factors showed that immobility was found in 13 (22%) patients in the thrombolytic group. Of these patients, 4 had surgical history and 4 had immobilization due to trauma history. In the anticoagulation group, immobilization was found in 17 (44.7%) patients. Immobilization was observed in 5 patients with surgical history and in 4 patients after trauma. There was a statistically significant difference between the two groups respect to immobility (p=0.013). There was no contraindication for thrombolysis in the patients having history of surgery and trauma. There was no significant difference between the two groups for DVT and travel history. 4.2.2. Patients’ Vital Signs The thrombolytic group and the anticoagulation group were similar in terms of systolic arterial blood pressure, mean arterial blood pressure, PaO 2 /FiO 2 ratio measured before treatment on the admission day. The pulse rate per minute on the admission was higher in the thrombolytic group (Table 2). Table 2 . Vital signs of the thrombolytic and anticoagulation group on the admission day, before treatment Parameters Thrombolytic Group (n=59) Anticoagulation Group (n=38) p value Admission day systolic BP, (mmHg) 121 (105-130) 122 (112-140) 0,14 Admission day mean BP, (mmHg) 88 (80-100) 89 (85-100) 0,45 Admission day pulse /min 116 (105-127) 107 (86-121) 0,032 Admission day PaO 2 /FiO 2 330 (270-380) 293 (255-389) 0,45 All data are provided as median (Iq25-Iq75). Abbreviations: BP: Blood Pressure, PaO 2 /FiO 2 ratio: Arterial Partial Oxygen Pressure/ Fractionated Oxygen ratio. Table 3. Evaluation of the differences in the vital signs of patients in thrombolytic and anticoagulation groups on the admission day and the second day Thrombolytic Group (n=59) Anticoagulation Group (n=38) Parameters Admission Day Second Day p value Admission Day Second Day p value Systolic BP, (mmHg) 121 (105-130) 123 (114-132) 0,15 122 (112-140) 128 (111-141) 0,64 Mean BP, (mmHg) 88 (80-100) 87 (82-95) 0,82 89 (85-100) 92 (80-101) 0,63 Pulse /min 116 (105-127) 91 (80-104) <0,001 107 (86-121) 94 (80-101) <0,001 PaO 2 /FiO 2 330 (270-380) 417 (351-447) <0,001 293 (255-389) 351 (263-384) 0,27 All data are provided as median (Iq25-Iq75). Abbreviations: BP: Blood Pressure, PaO 2 /FiO 2 ratio: Arterial Partial Oxygen Pressure / Fractionated Oxygen ratio. Table 3 presents the changes in the vital signs of each group after treatment. While there were significant improvements in oxygenation (p<0.001) and pulse rates (p<0.001) on the second day in the patients treated with thrombolysis; the decreased pulse rate was observed in the group receiving anticoagulants (p<0.001). There was no significant change in systolic and mean blood pressure measurements in both groups (Table 3). 4.2.3. Comparison of Complications and Mortality Statistically significant differences were not found in the comparison of complications related to treatment in two groups. No major bleeding was detected. The duration of hospitalization was similar in two groups; while the length of intensive care unit was shorter in the anticoagulation group compared to the thrombolytic group (p <0,001) (Table 4). Table 4: Complications and complication rates, intensive care and hospitalization times of the thrombolytic and anticoagulation groups Parameters Thrombolytic Group (n=59) Anticoagulation Group (n=38) p value Complication present, n (%) 5 (8,5) 2 (5,3) 0,70 Complication types -Hematoma -Hematuria -Unexplained hemoglobin drop -Hemoptysis -HIT 1 (1,7) 1 (1,7) 1 (1,7) 2 (3,4) - - 1 (2,6) - - 1 (2,6) In-hospital mortality, n (%) 4 (6,7) 5 (13,1) 0,73 Duration of intensive care unit (day) * 3,0 (2,0-4,0) 1,5 (0-2,25) <0,001 Duration of hospital stay (day) * 9,0 (6,0-11,0) 8,0 (6,0-12,0) 0,69 *: median (Iq25-Iq75) Abbreviations: HIT: Heparin Induced Thrombocytopenia. The anticoagulant preparation to be used for maintenance treatment was decided by the attending physician. Treatment durations were determined according to the underlying causes. There was no difference between the two groups in terms of CPTE and CTEPH. Of these, 43 patients in the thrombolytic group and 26 patients in the anticoagulation group were followed up regarding CPTE and CTEPH. One-month mortality rate was found to be 6,8% in the half-dose thrombolytic group and 15,8% in the anticoagulation group. Even though mortality ratio was lower in the thrombolytic group, this difference was not statistically significant. Also, one-year mortality rate was found as 13.7% and 26.3% respectively (p=0.17) (Table 5). Table 5. Mortality rates and long-term complications in the thrombolytic group and anticoagulation group Parameters, n (%) Thrombolytic Group (n=59) Anticoagulation Group (n=38) p value One month mortality 4/59 (6,7) 6/38 (15,8) 0,18 One year mortality * 7/51 (13,7) 10/38 (26,3) 0,17 Chronic Pulmonary Thromboembolism ** 4/43 (9,3) 1/23 (4,3) 0,65 Chronic Thromboembolic Pulmonary Hypertension ** 2/43 (4,3) 1/23 (4,3) 1,0 Re-embolism *** 1/46 (2,2) 3/32(9,4) 0,30 * Mortality was evaluated in 51 patients whose follow-up period was completed. ** Patients with missing data were not included in this analysis, only 66 patients were assessed. *** Re-embolism: There were 78 patients followed for recurrent embolism. DISCUSSION This study compared half-dose alteplase and LMWH for initial treatment in patients diagnosed with intermediate-high risk PE. The one-month and one-year mortality rates were found to be lower in the thrombolytic group compared to the anticoagulation group, but these differences were not statistically significant. According to Pulmonary Thromboembolism Guidelines of the European Society of Cardiology/European Respiratory Society, these two pharmacological agents were compared for the first time in the intermediate-high risk PE group, and no significant difference was observed between the groups in terms of major bleeding, minor bleeding, and long-term complications. Intermediate-high risk PE group has a higher mortality risk compared to intermediate-low group because this group has increased risk for developing right ventricle failure without hemodynamic decompensation. ESC/ERS guideline suggests anticoagulant therapy and close follow-ups in this patient group. The guideline recommends fibrinolytic treatment in case hemodynamic decompensation develops. The American Society of Hematology does not recommend the routine use of thrombolytics in hemodynamically stable patients with right heart failure. The most important reason for not making recommendations in favour of thrombolytics in these guidelines is the lack of sufficient data. (2,11). On the other hand, the use of thrombolytics for intermediate-high risk PE patients is often discussed by “Pulmonary Embolism Response Teams” (12,13). In our clinical practice, patients in this group are treated with half-dose thrombolytic therapy after the establishment of EGEPET unless contraindicated. In their study, Mirambeaux et al. followed 1015 hemodynamically stable patients prospectively. According to results, intermediate-high risk PE was found in 97 (9.6%) of the patients based on the ESC/ERS PE guideline. The one-month all-cause mortality in this patient group was 24% (14). In our presented study, mortality rate was 6,7% in the thrombolytic group and 15,8% in the anticoagulation group. However, the contribution of the application of reperfusion therapy to low mortality rate in these series cannot be confirmed because of the limited number of patients. Arterial hypotension, tachycardia, low partial oxygen pressure and low oxygen saturation parameters are seen as risk factors for short-term (30-day) mortality in the literature in addition to hemodynamic instability (15,16). Declined blood pressure and PaO 2 /FiO 2 ratio, and increased pulse value are accepted as poor prognosis signs during follow-up. In our study, vital signs of patients were similar in both groups on the admission day; but after half-dose thrombolytic treatment, significant decreases in pulse rate per minute and significant increases in PaO 2 /FiO 2 value were observed, pointing to clinically rapid improvement in the thrombolytic group. But this response did not affect the long-term results. Both thrombolytic therapy and anticoagulation therapy have well-recognized complications. The most common complication for both treatments is bleeding. Meta-analysis made by Zuo et al. has shown that thrombolysis increases major bleeding by 2.84 times and minor bleeding by 2.97 times compared to the anticoagulation (17). Although there is evidence that thrombolytic therapy increases the risk of bleeding, it has also been shown that thrombolytic therapy corrects signs of right ventricle failure more rapidly and effectively (4). In this situation, making a decision to use thrombolytic therapy, which is a risky treatment, becomes an important clinical problem. When studies evaluating patient groups similar to the present study are analyzed, different results are observed between thrombolytic and anticoagulation therapy. The meta-analysis conducted on eleven studies by Riera-Mestre et al. analyzed the efficacy and side-effects of the thrombolytic therapy. It was observed that in these studies, a reduced dose of alteplase was used in seven studies used, Tenecteplase was used in three studies, and urokinase was used in one study. Research results showed that thrombolysis did not reduce mortality risk, but increased bleeding risk by 2.83 times. In addition, it was concluded that thrombolytic therapy increased the risk of intracranial hemorrhage by 2.36 times, although this result was not statistically significant. With these results, the authors do not recommend the use of thrombolytics in intermediate-risk PE (18). In this meta-analysis, the patients were not classified as intermediate-high and intermediate-low risk according to new guidelines. However, there are also other studies reporting that thrombolytic therapy does not increase the risk of bleeding compared to anticoagulation therapy. (19). In the present study, no major bleeding was observed, and no difference was found between the anticoagulant (5.3%) and thrombolytic (8.5%) groups in terms of minor bleeding. Meyer et al. investigated Tenecteplase and unfractionated heparin treatments among PE patients with right ventricular failure and elevated troponin. Tenecteplase 30-50 mg was used (the dose used in acute myocardial infarction) as a thrombolytic and compared with the unfractionated heparin treatment group. The primary endpoint of this study was the development of hemodynamic decompensation 7 days after randomization. While hemodynamic decompensation was found to develop in 13 patients (2.6%) in the thrombolytic group, it was observed in 28 patients (5.6%) treated with heparin (p=0.02). However, this result was not significant in the patient subgroups younger than 75. There was important bleeding in the thrombolytic group. In addition, the 30-day mortality rate was 2.4% in the thrombolytic group and 3.2% in the anticoagulation group, and this outcome was not statistically significant (4). Although the case definitions here were similar the present study, the patients having hemodynamic decompensation during follow-up and whose thrombolytic therapy was completed to full dose were excluded in our analysis. And different thrombolytic agents were used in these two studies. The MOPETT study compared the efficacy of thrombolytic therapy with low-dose tissue plasminogen activator and anticoagulant in patients with intermediate-risk. Heparin infusion or enoxaparin was administered for anticoagulation therapy. In MOPETT trial, intermediate risk PE was defined as clinical findings of PE and the presence of severe radiological PE (more than 70% involvement in more than two lobar arteries in CTPA or presence of involvement in the main pulmonary artery or involvement of more than two lobes in V/P scintigraphy). This definition is different from the intermediate-high risk PE diagnosis in the ESC/ERS guideline which was used in our study. The hospital mortality rate was 1.6% in the thrombolytic group and 5% in the anticoagulation group. While no recurrent embolism occurred in the thrombolytic arm, 5% of the anticoagulation arm had recurrent embolism (p=0.08). No bleeding was observed in both groups. The hospital mortality rate in our study and the frequency of recurrent emboli were higher compared to MOPETT study. Recurrent embolism rate in both studies were lower in the thrombolytic arm than the anticoagulation arm. But these differences were not significant. We have to remember that in the MOPETT study, right ventricle failure and troponin positivity were not assessed, the patients were classed into only radiological findings rather than clinical severity. (20). Moreover, our patient group was older than MOPETT trial group and was evaluated with Charlson Comorbidity Index. In MOPETT, while there was no difference between the groups in terms of the presence of one-to-one comorbidity, the burden of all comorbidities was not seemed to be evaluated. In Türkiye, Yılmaz et al. compared the efficacy of LMWH and 50 mg alteplase in patients with PE who were hemodynamically stable but had right ventricle failure findings in CTPA or ECHO. There were 38 patients in each group. One death (3%) occurred in the thrombolytic group within 30 days, while death was observed in 4 (10%) patients in the anticoagulation group (p=0.36). When the development of hemodynamic decompensation or death in the first 30 days was considered together, hemodynamic decompensation/death was observed in 1 patient in the thrombolytic group and in 10 patients in the anticoagulation group (p=0.009). In other words, one-month mortality was not affected by half-dose alteplase, but the development of hemodynamic decompensation could be prevented. Although similar in design to our study, biomarkers were not used in this study as indicators of cardiac damage (6). Analysis of the RIETE database showed that the average length of hospitalization in acute PE decreased from 13.6 days in 2001 to 9.3 days in 2013 (p<0,001). This may be explained by the increased popularity of out-patient follow-up in recent years and more frequent use of LMWH treatment instead of unfractioned heparin (21). In our study, the duration of hospitalization was similar to the literature and there was no difference between the groups, however the duration of intensive care stay was longer in the thrombolytic group. This difference may be due to the fact that nowadays the intermediate-high risk patient group in terms of mortality may switch to the high mortality group within the first 24-48 hours and these patients are followed up in the intensive care unit. In addition, patients given thrombolytics should be followed closely for bleeding. All of these may contribute to the length of hospitalization in the intensive care unit. The historical control group in the present study, which received anticoagulants, were mostly followed up in the ward or had short-term intensive care unit hospitalizations. Findings of right ventricular failure and large thrombus in the pulmonary arteries increase the risk of CTEPH (22). The results of the study following 219 patients with intermediate risk PE presented that 13.2% of patients develop right ventricular dysfunction on ECHO after CTEPH status or post-PE impairment (23). Although thrombolytic therapy is thought to be protective against CPTE or CTEPH, more data are needed on this subject. When the MOPETT study was analyzed in terms of the development of pulmonary hypertension (Systolic Pulmonary Artery Pressure above 40 mmHg on ECHO), the rate of development of pulmonary hypertension during follow-up was 57% in the group receiving anticoagulation and 16% in the group receiving thrombolytics (p<0.001) (20). In the present study, the rates of CPTE or CTEPH were the same between the two groups, but it should be remembered that the follow-up period was longer in patients receiving anticoagulants. It was observed that thrombolytic therapy was used for intermediate-high risk patients more intensively after the establishment of EGEPET. This study, which aimed to investigate the efficacy of reperfusion therapy with alteplase as half dose, has some limitations. First, this study is single-centered and should be interpreted with caution in terms of generalizing the results. Second, since the number of patients planned at the beginning of the study could not be reached, therefore, the targeted study power could not be achieved. Since the intermediate-high-risk group is less common in acute PE compared to other risk classes, the total number of patients remained at 97 during the seven-year period. Third, the prospectively enrolled thrombolytic case arm was followed up closely, whereas anticoagulant group data were obtained retrospectively from patient records. Patients who received anticoagulation treatment after the establishment of EGEPET were excluded for preventing selection bias. Fourth, this study was not designed as a randomized controlled trial, but the analyses showed that the groups were similar in terms of demographic and clinical findings at admission. Fifth, patients whose hemodynamic deteriorated following reperfusion therapy with half-dose thrombolytics or who received full dose thrombolytics due to increased oxygen demand were excluded. Sixth, the follow up of complications proved to be more difficult due to COVID-19 pandemic, especially in the years 2020-2021. However, we should remember that this is a real-life study. CONCLUSION The issue of "whether anticoagulants should be used in treatment or reperfusion therapy with thrombolytics" in intermediate-high risk patients with acute PE is still a controversial issue. Guidelines recommend using anticoagulation therapy initially and using thrombolytic therapy if hemodynamic decompensation develops. However, they also point that the level of evidence is not sufficient for this recommendation. In recent years, studies were published describing the experiences of multidisciplinary Pulmonary Embolism Response Teams and initial thrombolytic therapy in hemodynamically stable patients with right ventricle failure. Our study is the first study comparing the efficacy of 50 mg Alteplase and LMWH in the intermediate-high risk group for early mortality as classified by the latest ESC/ERS guideline and concluded that PaO2/FiO2 ratio improved significantly after thrombolytic therapy compared to the anticoagulant group. Major bleeding did not develop as a complication in both groups. Although one-month and one-year mortality was found to be lower in the thrombolytic group, it did not reach statistical significance. Multicenter, randomized controlled studies are needed in this group of patients who have the risk of transition to the massive embolism group within the first 48 hours. Declarations Author Declarations Funding: The funding sources had no role in the design and conduct of the study; and also funding sources had no role in the collection, management, analysis, and interpretation of the data. Not any funding sources had used in this manuscript. Conflict of Interest Disclosures: The authors declare no conflict of interest to declare relevant to the content of this manuscript. Availability of data and material : The data of this article is available and can be shared whenever requested. Code availability (software application or custom code): Not Applicable Author Contributions : Study concept and design: FB, PKE, ÖSU and ME. Acquisition, analysis, or interpretation of data: PKE, ÖSU, AÇ, ÖC and ES. Drafting of the manuscript: SB, RS, GÇ, TY and ÇE. Critical revision of the manuscript for important intellectual content: ÖSU, PKE, MU, TY and KD. Statistical analysis: PKE, ÖSU. Administrative, technical, or material support: FKA, SN, AÇ, GÇ and ÇE. Study supervision: FB, ME, GÇ, and RS. Ethics approval (include appropriate approvals or waivers ): The study was approved by the Clinical Research Ethics Committee of Ege University Faculty of Medicine (22-4.3/26) and by Republic of Türkiye Ministry of Health, Turkish Medicines and Medical Devices Agency (21-AKD-107). Consent to participate (include appropriate statements): Informed consent of the patients was obtained. We keep the signed informed consent of patients. Consent for publication (include appropriate statements): Informed consent of the patients was obtained. We keep the signed informed consent of patients. References Raskob GE, Angchaisuksiri P, Blanco AN, Büller H, Gallus A, Hunt BJ et al. Thrombosis: a major contributor to global disease burden. Semin Thromb Hemost [Internet]. 2014 Oct 31 [cited 2022 Oct 23];40(7):724–35. Available from: http://www.ncbi.nlm.nih.gov/pubmed/25302681 . Konstantinides SV, Meyer G, Bueno H, Galié N, Gibbs JSR, Ageno W et al. 2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS)The Task Force for the diagnosis and management of acute pulmonary embolism of the European Society of C. Eur Heart J [Internet]. 2020 Jan 21 [cited 2022 Oct 23];41(4):543–603. Available from: https://academic.oup.com/eurheartj/ article/41/4/543/5556136. Elias A, Mallett S, Daoud-Elias M, Poggi JN, Clarke M. Prognostic models in acute pulmonary embolism: a systematic review and meta-analysis. BMJ Open [Internet]. 2016 [cited 2023 Mar 14];6(4). Available from: https://pubmed.ncbi.nlm.nih.gov/27130162/ . Meyer G, Vicaut E, Danays T, Agnelli G, Becattini C, Beyer-Westendorf J et al. Fibrinolysis for Patients with Intermediate-Risk Pulmonary Embolism. N Engl J Med [Internet]. 2014 Apr 10 [cited 2022 Nov 29];370(15):1402–11. Available from: https://www.nejm.org/doi/full/ 10.1056/NEJMoa1302097 . Marti C, John G, Konstantinides S, Combescur C, Sanchez O, Lankeit M et al. Systemic thrombolytic therapy for acute pulmonary embolism: a systematic review and meta-analysis. Eur Heart J [Internet]. 2015 Mar 7 [cited 2023 Mar 13];36(10):605–14. Available from: https://pubmed.ncbi.nlm.nih.gov/24917641/ . Yilmaz ES, Uzun O. Low-dose thrombolysis for submassive pulmonary embolism. J Investig Med. 2021;69(8):1439–46. Pisters R, Lane DA, Nieuwlaat R, De Vos CB, Crijns HJGM, Lip GYH et al. A novel user-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in patients with atrial fibrillation: the Euro Heart Survey. Chest [Internet]. 2010 Nov 1 [cited 2023 Mar 19];138(5):1093–100. Available from: https://pubmed.ncbi.nlm.nih.gov/20299623/ . Ruíz-Giménez N, Suárez C, González R, Nieto JA, Todolí JA, Samperiz ÁL et al. Predictive variables for major bleeding events in patients presenting with documented acute venous thromboembolism. Findings from the RIETE Registry. Thromb Haemost [Internet]. 2008 Jul [cited 2023 Mar 19];100(1):26–31. Available from: https://pubmed.ncbi.nlm.nih.gov/18612534/ . Schulman S, Anger SU, Bergqvist D, Eriksson B, Lassen MR, Fisher W. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in surgical patients. J Thromb Haemost [Internet]. 2010 Jan 1 [cited 2023 Mar 16];8(1):202–4. Available from: https://onlinelibrary.wiley.com/doi/full/ 10.1111/j.1538-7836.2009.03678.x . Lachant DJ, Bach C, Fe A, White RJ, Lachant NA. Direct oral anticoagulant therapy in patients with morbid obesity after intermediate- or high-risk pulmonary emboli. ERJ Open Res [Internet]. 2021 Jan 1 [cited 2022 Nov 24];7(1):00554–2020. Available from: https://openres.ersjournals.com/content/7/1/00554-2020 . Ortel TL, Neumann I, Ageno W, Beyth R, Clark NP, Cuker A et al. American Society of Hematology 2020 guidelines for management of venous thromboembolism: treatment of deep vein thrombosis and pulmonary embolism. Blood Adv [Internet]. 2020 Oct 10 [cited 2022 Dec 2];4(19):4693. Available from: /pmc/articles/PMC7556153/ . Kabrhel C, Rosovsky R, Channick R, Jaff MR, Weinberg I, Sundt T et al. A Multidisciplinary Pulmonary Embolism Response Team: Initial 30-Month Experience With a Novel Approach to Delivery of Care to Patients With Submassive and Massive Pulmonary Embolism. Chest [Internet]. 2016 Aug 1 [cited 2023 Mar 12];150(2):384–93. Available from: https://pubmed.ncbi.nlm.nih.gov/27006156/ . Dudzinski DM, Piazza G. Multidisciplinary pulmonary embolism response teams. Circulation [Internet]. 2016 Jan 5 [cited 2023 Mar 12];133(1):98–103. Available from: https://www.ahajournals.org/doi/abs/ 10.1161/CIRCULATIONAHA.115.015086 . Mirambeaux R, León F, Behnood Bikdeli Ã, Morillo R, Barrios D, Mercedes E et al. Intermediate-High Risk Pulmonary Embolism. TH Open [Internet]. 2019 Oct [cited 2023 Apr 2];03(04):e356–63. Available from: http://www.thieme-connect.com/products/ejournals/html/10.1055/s -0039-3401003. Goldhaber SZ, Visani L, De Rosa M. Acute pulmonary embolism: clinical outcomes in the International Cooperative Pulmonary Embolism Registry (ICOPER). Lancet. 1999;353(9162):1386–9. Abdelfattah RA, Mohamed AH, Ali YM, Abdel Aziz MO, Abdullah NM, Asklany HT et al. Predictors of Short-Term Mortality in Patients with Acute Pulmonary Embolism. Egypt J Hosp Med [Internet]. 2022 Jul 1 [cited 2023 Mar 18];88(1):4101–5. Available from: https://ejhm.journals.ekb.eg/article_254833.html . Zuo Z, Yue J, Dong BR, Wu T, Liu GJ, Hao Q. Thrombolytic therapy for pulmonary embolism. Cochrane Database Syst Rev [Internet]. 2021 Apr 15 [cited 2023 Mar 18];2021(4). Available from: https://www.cochranelibrary.com/cdsr/doi/ 10.1002/14651858.CD004437.pub6/full . Riera-Mestre A, Becattini C, Giustozzi M, Agnelli G. Thrombolysis in hemodynamically stable patients with acute pulmonary embolism: A meta-analysis. Thromb Res. 2014;134(6):1265–71. Becattini C, Agnelli G, Salvi A, Grifoni S, Pancaldi LG, Enea I, et al. Bolus tenecteplase for right ventricle dysfunction in hemodynamically stable patients with pulmonary embolism. Thromb Res. 2010;125(3):e82–6. Sharifi M, Bay C, Skrocki L, Rahimi F, Mehdipour M. Moderate Pulmonary Embolism Treated With Thrombolysis (from the MOPETT Trial). Am J Cardiol. 2013;111(2):273–7. Jiménez D, De Miguel-Díez J, Guijarro R, Trujillo-Santos J, Otero R, Barba R et al. Trends in the Management and Outcomes of Acute Pulmonary Embolism Analysis from the RIETE Registry. J Am Coll Cardiol [Internet]. 2016 Jan 19 [cited 2023 Mar 26];67(2):162–70. Available from: https://www.jacc.org/doi/ 10.1016/j.jacc.2015.10.060 . Lang IM, Simonneau G, Pepke-Zaba JW, Mayer E, Ambrož D, Blanco I et al. Factors associated with diagnosis and operability of chronic thromboembolic pulmonary hypertension. A case-control study. Thromb Haemost [Internet]. 2013 [cited 2023 Apr 3];110(1):83–91. Available from: https://pubmed.ncbi.nlm.nih.gov/23677493/ . Barco S, Russo M, Vicaut E, Becattini C, Bertoletti L, Beyer-Westendorf J et al. Incomplete echocardiographic recovery at 6 months predicts long-term sequelae after intermediate-risk pulmonary embolism. A post-hoc analysis of the Pulmonary Embolism Thrombolysis (PEITHO) trial. Clin Res Cardiol [Internet]. 2019 Jul 1 [cited 2023 Apr 3];108(7):772–8. Available from: https://link.springer.com/article/ 10.1007/s00392-018-1405-1 . 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Fakultesi","correspondingAuthor":false,"prefix":"","firstName":"Cagatay","middleName":"","lastName":"ENGİN","suffix":""}],"badges":[],"createdAt":"2023-10-19 09:58:37","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3466076/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3466076/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":51082209,"identity":"46381400-de52-4b9d-95de-757569556a4a","added_by":"auto","created_at":"2024-02-13 19:24:15","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":30477,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eIdentification of the patient population\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAbbreviations: EGEPET: Ege Pulmonary Emboli Team; PE: Pulmonary Thromboembolism\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-3466076/v1/4048b098fe6f9a65f272dcf4.png"},{"id":51082212,"identity":"ee50fef5-14e3-411d-8fd2-d076caabb396","added_by":"auto","created_at":"2024-02-13 19:24:16","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":77610,"visible":true,"origin":"","legend":"\u003cp\u003eThe distribution of sPESI scores of the cases in the thrombolytic and anticoagulation groups\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-3466076/v1/3a41ec2e93c93df0cdc5b56a.png"},{"id":54645588,"identity":"996016b6-90dc-4bc5-a677-a140c6fbf926","added_by":"auto","created_at":"2024-04-14 11:18:14","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":635129,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3466076/v1/ca6193d5-4db5-4d3a-9a39-4b494bedd332.pdf"}],"financialInterests":"","formattedTitle":"Half Dose Alteplase or Low Molecular Weight Heparin in Pulmonary Embolism with Intermediate-High risk: Real life Study at Tertiary Hospital","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eAcute Pulmonary Embolism (PE) is a disease with high mortality and requires rapid intervention. The increased pulmonary vascular resistance due to filling of pulmonary arteries with embolism, right heart ventricle failure and hemodynamic decompensation can cause death. Deaths occurred by PE ranks the 3rd among cardiovascular diseases (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e Acute PE is classified as low, intermediate, high risk in terms of mortality based on the guidelines of European Respiratory Society/European Society of Cardiology. The patients in low risk is treated with anticoagulant treatment initially whereas fibrinolytic/reperfusion therapy is preferred in high-risk patients (hemodynamically unstable patients). Intermediate risk PE group is divided into two classes which are intermediate-high risk and intermediate-low risk. Elias et al. found the frequency of intermediate-low risk PE as 56% and intermediate-high PE as 9,6%. The literature has shown that the frequency of intermediate-high risk is low, but it has high mortality rate. For this reason, the guidelines recommend that intermediate-high risk patients (patients who are hemodynamically stable but have right ventricle failure) should be investigated as a separate group (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe study comparing Tenecteplase and Unfractionated Heparin in patients with radiological evidence of right ventricle failure (CTPA or ECO) and having cardiac injury documented by troponin elevation, has found that hemodynamic decompensation occurs less in the thrombolytic group but bleeding is detected at higher rates (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). In the meta-analysis which contains all patients with intermediate risk, Marti et al. has pointed that thrombolysis does not provide additional benefits also it increases bleeding risk compared to initial anticoagulation treatment (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). There is no statistically significant difference between the efficacy of thrombolysis and low molecular weight heparin (LMWH) in hemodynamically stable patients with right ventricle failure proven by CTAP or ECO without the evaluation of cardiac biomarkers (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eAccording to literature, there is no sufficient and accurate data about the treatment of intermediate-high risk PE patients. Hence, this study aimed to compare the administration of half-dose Alteplase and LMWH in intermediate-high risk PE patients by evaluating the effect of half-dose Alteplase in one-month and one-year all-cause mortality and assessing treatment complications.\u003c/p\u003e"},{"header":"MATERIALS and METHODS","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e3.1. Study Protocol\u003c/h2\u003e \u003cp\u003eThis observational, single-centered study was designed with prospective and retrospective stages. The patients diagnosed with PE at Ege University Medical Faculty Hospital between 01.01.2016\u0026ndash;13.02.2023 and classified as intermediate-high risk group according to the 2019 ERS/ESC guidelines were included in the study.\u003c/p\u003e \u003cp\u003e The study was approved by the Clinical Research Ethics Committee of Ege University Faculty of Medicine (22\u0026thinsp;\u0026minus;\u0026thinsp;4.3/26) and by Republic of T\u0026uuml;rkiye Ministry of Health, Turkish Medicines and Medical Devices Agency (21-AKD-107).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e3.2. Patient Population\u003c/h2\u003e \u003cp\u003eEge Pulmonary Embolism Team (EGEPET) was established on 2.10.2018 in Ege University Faculty of Medicine for rapid diagnosis and treatment of PE.\u003c/p\u003e \u003cp\u003eThe patients, evaluated at EGEPET between 02.10.2018 and 13.02.2023 and diagnosed with intermediate-high risk PE and treated with half dose thrombolysis, were included in the study prospectively. Prior to the establishment of EGEPET, patients who were diagnosed with intermediate-high PE between 01.1.2016\u0026ndash;2.10.2018 and were treated with only anticoagulation were included in the study retrospectively.\u003c/p\u003e \u003cp\u003e \u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eInclusion Criteria\u003c/span\u003e: Patients aged 18 years or older, whose PE was confirmed with CTPA or V/P scintigraphy, patients classified as intermediate-high risk in terms of early mortality, and patients who received half-dose thrombolysis were included in the prospective group. The patients treated with LMWH were included in the retrospective group. The patients provided informed consent forms to participate in the study.\u003c/p\u003e \u003cp\u003e \u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eExclusion Criteria\u003c/span\u003e: The patients with missing data, the patients whose right ventricle failure could not be documented clearly, the patients having contraindication for thrombolysis, the patients who were given full-dose thrombolysis because of hemodynamic instability in the emergency department during follow-up after initial treatment, the patients who received half-dose thrombolysis and whose treatment was completed to the full dose due to clinical findings in the follow-up, the patients who were not suitable for thrombolysis administration due to the high risk of bleeding with the decision of EGEPET and the patients who had unstable comorbidities that may have effects on mortality (etc. malignancy or general medical condition) were excluded from the study.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e3.3. Pulmonary Embolism Diagnosis, Mortality Status Evaluation and Bleeding Risk Scoring\u003c/h2\u003e \u003cp\u003ePulmonary embolism was diagnosed with CTPA or V/P scintigraphy. The sPESI score was calculated with the comorbidities and vital parameters of the hemodynamically stable patients. The right ventricular failure was evaluated with CTPA or Echocardiography. Troponin was used to assess right ventricular functions.\u003c/p\u003e \u003cp\u003eIntermediate-high risk group was defined as patients with sPESI score\u0026thinsp;\u0026ge;\u0026thinsp;1 and evidence of right ventricular failure on ECHO or BTPA and elevated troponin or patients with sPESI score 0 and right ventricular dysfunction detected by imaging methods and biomarkers. The risk classification of the patients was discussed and decided at EGEPET. The early mortality risk for the patients before the establishment of EGEPET was performed retrospectively according to ESC/ERS PE guideline (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eRIETE and HAS-BLED scores were calculated and recorded for bleeding risk. (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003e3.4. Treatment Decision and Method of Application\u003c/h2\u003e \u003cp\u003eThe treatments of the patients included in the prospective group were determined by the EGEPET group, available 24/7 using the Whatsapp\u0026reg; application, and the treatments of the cases in the retrospective period were determined by the physicians who monitored them.\u003c/p\u003e \u003cp\u003eAs thrombolytic therapy for the introspective group, 50 mg alteplase was administered by intravenous infusion over two hours. After alteplase, the anticoagulant treatments of patients were continued by LMWH.\u003c/p\u003e \u003cp\u003eIf the kidney function test was not impaired, anticoagulation was used in the retrospective group as 2x0.100 anti-XA IU/kg (e.g., 2x6000 IU for a 60 kg patient) Enoxaparin was administered subcutaneously.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003e3.5. Evaluation of Complications\u003c/h2\u003e \u003cp\u003eHemorrhagic stroke, major bleeding, minor bleeding, and heparin-associated thrombocytopenia (HIT) were evaluated as treatment complications.\u003c/p\u003e \u003cp\u003eMajor bleeding: Bleeding in critical organs (intracranial, intraocular, pericardial hemorrhage), and a decrease in hemoglobin more than 2 g/dL were considered as fatal bleeding that led to death within 7 days. Minor bleeding was also assessed as bleeding other than major bleeding that affected the clinical status of the patient albeit to a lesser extent (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eChronic Pulmonary Thromboembolism (CPTE): The patients who received maintenance anticoagulation therapy at an effective dose for 3 months but still had evidence of PE on CTPA or V/P Scintigraphy were defined as having \"Chronic Pulmonary Thromboembolism (CPTE)\" (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). In case that the patients had both CPTE and right ventricle failure findings at echocardiograph, they were diagnosed with Chronic Thromboembolic Pulmonary Hypertension (CTEPH), after the exclusion of other possible pulmonary hypertension causes. Recurrent Pulmonary Thromboembolism (Re-Emboli) was defined as re-development of PE in patients with clinical relief after the diagnosis of pulmonary thromboembolism (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eMortality was evaluated as one-month and one-year all-cause mortality after the diagnosis time of PE.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003e3.6. Collection and Recording of Study Data\u003c/h2\u003e \u003cp\u003ePatient data during the EGEPET period was recorded from the electronic patient file without any intervention. Information of the patients diagnosed before EGEPET was obtained retrospectively using electronic patient files or written patient files. All of the data were recorded the prepared data form.\u003c/p\u003e \u003cp\u003eAge, gender, smoking status, comorbidities, PE risks, Charlson Comorbidity Index, admission clinical and laboratory parameters, and sPESI scores of all patients were recorded after applying inclusion and exclusion criteria. Systemic arterial blood pressure, pulse and oxygenation status on the admission day (before treatment) and second days of treatment; complications, mortality status were evaluated.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003e3.7. Statistics\u003c/h2\u003e \u003cp\u003eStatistical analyzes were made with SPSS (Statistical Package for Social Sciences) 20.0 program. The distributions of the variables were evaluated with the \u0026ldquo;Kolmogorov-Smirnov and Shapiro-Wilk Test\u0026rdquo;. While numerical data were presented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation or median (Iq25-Iq75) value, categorical variables were presented as \u0026ldquo;%\u0026rdquo;.The parameters that fit the normal distribution were compared by Student-t test and the parameters that did not fit the normal distribution were compared by Mann-Whitney U test, which is a nonparametric test. Chi-square or Fisher Exact test was used to compare categorical variables.\u003c/p\u003e \u003cp\u003eThe power analysis before the study had indicated that for get an effective result sample size should be 160 patients on both groups. In the prospective part of the study, we evaluated 265 patients and, in the retrospective part of the study we evaluated 366 patients. The number of patients which intermediate-high risk PE and carries inclusion and exclusion criteria was 59 and that number was 38.\u003c/p\u003e \u003cp\u003eThe comparison of the parameters evaluated on the admission and second days of the treatment was performed with the Wilcoxon test. The value of \u0026ldquo;p\u0026thinsp;\u0026lt;\u0026thinsp;0.05\u0026rdquo; was accepted as statistically significant.\u003c/p\u003e \u003c/div\u003e"},{"header":"RESULTS","content":"\u003ch2\u003e4.1. Patient Population\u003c/h2\u003e\n\u003cp\u003eProspectively, 59 patients who were diagnosed with medium-high-risk PE during the EGEPET period and received half-dose\u0026nbsp;thrombolysis\u0026nbsp;were included in the study as \u0026quot;thrombolytic group\u0026quot;.\u003c/p\u003e\n\u003cp\u003eFor the \u0026quot;anticoagulant group\u0026quot;, 366 patients diagnosed with PE and hospitalized in the Ege University Medical Faculty Pulmonary Diseases Service or Intensive Care Unit between January 2016 and October 2018 were screened retrospectively. Thirty-eight patients were classified as intermediate-high risk PE, meeting the criteria for this study (Figure 1).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFigure 1: Identification of the patient population\u003c/strong\u003e\u003c/p\u003e\n\u003ch2\u003e4.2. Findings of Patients in the Thrombolytic Group and Anticoagulation Group\u003c/h2\u003e\n\u003ch2\u003e4.2.1 Patients\u0026rsquo; Demographic and Clinical Characteristics \u003c/h2\u003e\n\u003cp\u003ePE diagnosis was done with CTPA in the majority of the patients (98%). Only one patient was examined with V/P scintigraphy. Another patient could not undergo CT, due to being morbidly obese, and therefore PE was diagnosed with presence of right ventricle\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003efailure on echocardiography and DVT on Doppler USG.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe median age of two groups were similar, but the female ratio in thrombolytic group was higher compared to the other group (45,8% vs 68,4% and p=0.037). All patients in the thrombolytic group had bilateral PE. In the anticoagulation group, 35 patients (92.1%) had bilateral PE (p=0.59).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThere was no difference between the two groups regarding the comorbidities, sPESI score, RIETE and HAS-BLED bleeding scores and recurrent embolism history. The median Charlson Comorbidity Index value was 4 (2.0-5.75) in the anticoagulation group, whereas it was found as 3 (1.0-5.0) in the thrombolytic group (p=0.050). \u0026nbsp;The hemoglobin and d-dimer value were found to statistically significant between the two groups (Table 1). Figure 2 presents the sPESI distribution of both groups.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 1.\u003c/strong\u003e Demographic and clinical characteristics of the cases in the thrombolytic group and the anticoagulation group\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"600\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.5559265442404%\"\u003e\n \u003cp\u003e\u003cstrong\u003eParameters\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.03839732888147%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eThrombolytic Group (n=59)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.874791318864773%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eAnticoagulation Group (n=38)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.530884808013354%\"\u003e\n \u003cp\u003e\u003cstrong\u003ep value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.5559265442404%\" valign=\"top\"\u003e\n \u003cp\u003eAge, (year)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.03839732888147%\" valign=\"top\"\u003e\n \u003cp\u003e66 (51,0-73,0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.874791318864773%\" valign=\"top\"\u003e\n \u003cp\u003e68 (59,5-79,25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.530884808013354%\" valign=\"top\"\u003e\n \u003cp\u003e0,054\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.5559265442404%\" valign=\"top\"\u003e\n \u003cp\u003eFemale, \u003cem\u003en (%\u003c/em\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.03839732888147%\" valign=\"top\"\u003e\n \u003cp\u003e27 (45,8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.874791318864773%\" valign=\"top\"\u003e\n \u003cp\u003e26 (68,4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.530884808013354%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0,037\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.5559265442404%\" valign=\"top\"\u003e\n \u003cp\u003eComorbidities, \u003cem\u003en (%)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.03839732888147%\" valign=\"top\"\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.874791318864773%\" valign=\"top\"\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.530884808013354%\" valign=\"top\"\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.5559265442404%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; Hypertension\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.03839732888147%\" valign=\"top\"\u003e\n \u003cp\u003e30 (50,8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.874791318864773%\" valign=\"top\"\u003e\n \u003cp\u003e20 (54,1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.530884808013354%\" valign=\"top\"\u003e\n \u003cp\u003e0,84\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.5559265442404%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; Diabetes Mellitus\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.03839732888147%\" valign=\"top\"\u003e\n \u003cp\u003e11 (18,6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.874791318864773%\" valign=\"top\"\u003e\n \u003cp\u003e8 (21,6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.530884808013354%\" valign=\"top\"\u003e\n \u003cp\u003e0,79\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.5559265442404%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; Malignancy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.03839732888147%\" valign=\"top\"\u003e\n \u003cp\u003e9 (15,3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.874791318864773%\" valign=\"top\"\u003e\n \u003cp\u003e7 (18,4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.530884808013354%\" valign=\"top\"\u003e\n \u003cp\u003e0,78\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.5559265442404%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; Dementia, CVD, Alzheimer, \u0026nbsp; \u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; Parkinson\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.03839732888147%\" valign=\"top\"\u003e\n \u003cp\u003e7 (11,9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.874791318864773%\" valign=\"top\"\u003e\n \u003cp\u003e6 (15,8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.530884808013354%\" valign=\"top\"\u003e\n \u003cp\u003e0,76\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.5559265442404%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; Coronary Artery Disease\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.03839732888147%\" valign=\"top\"\u003e\n \u003cp\u003e6 (10,2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.874791318864773%\" valign=\"top\"\u003e\n \u003cp\u003e4 (10,8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.530884808013354%\" valign=\"top\"\u003e\n \u003cp\u003e1.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.5559265442404%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; CHF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.03839732888147%\" valign=\"top\"\u003e\n \u003cp\u003e1 (1,7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.874791318864773%\" valign=\"top\"\u003e\n \u003cp\u003e2 (5,3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.530884808013354%\" valign=\"top\"\u003e\n \u003cp\u003e0,56\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.5559265442404%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; Hypothyroidism\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.03839732888147%\" valign=\"top\"\u003e\n \u003cp\u003e3 (5,1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.874791318864773%\" valign=\"top\"\u003e\n \u003cp\u003e2 (5,3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.530884808013354%\" valign=\"top\"\u003e\n \u003cp\u003e1.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.5559265442404%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; Rheumatism Disease\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.03839732888147%\" valign=\"top\"\u003e\n \u003cp\u003e3 (5,1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.874791318864773%\" valign=\"top\"\u003e\n \u003cp\u003e3 (8,1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.530884808013354%\" valign=\"top\"\u003e\n \u003cp\u003e0,67\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.5559265442404%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; COPD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.03839732888147%\" valign=\"top\"\u003e\n \u003cp\u003e3 (5,1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.874791318864773%\" valign=\"top\"\u003e\n \u003cp\u003e2 (5,3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.530884808013354%\" valign=\"top\"\u003e\n \u003cp\u003e1.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.5559265442404%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; IPF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.03839732888147%\" valign=\"top\"\u003e\n \u003cp\u003e0\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.874791318864773%\" valign=\"top\"\u003e\n \u003cp\u003e1 (2,6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.530884808013354%\" valign=\"top\"\u003e\n \u003cp\u003e0,39\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.5559265442404%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; Renal Failure\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.03839732888147%\" valign=\"top\"\u003e\n \u003cp\u003e1 (3,4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.874791318864773%\" valign=\"top\"\u003e\n \u003cp\u003e1 (2,7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.530884808013354%\" valign=\"top\"\u003e\n \u003cp\u003e1.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.5559265442404%\" valign=\"top\"\u003e\n \u003cp\u003eCharlson Comorbidity Index*\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.03839732888147%\" valign=\"top\"\u003e\n \u003cp\u003e3,0 (1,0-5,0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.874791318864773%\" valign=\"top\"\u003e\n \u003cp\u003e4 (2,0-5,75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.530884808013354%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0,050\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.5559265442404%\" valign=\"top\"\u003e\n \u003cp\u003esPESI score*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.03839732888147%\" valign=\"top\"\u003e\n \u003cp\u003e2,0 (1,0-2,0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.874791318864773%\" valign=\"top\"\u003e\n \u003cp\u003e2,0 (1,0-2,0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.530884808013354%\" valign=\"top\"\u003e\n \u003cp\u003e0,95\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.5559265442404%\" valign=\"top\"\u003e\n \u003cp\u003eRIETE score*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.03839732888147%\" valign=\"top\"\u003e\n \u003cp\u003e2,0 (1,0-2,5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.874791318864773%\" valign=\"top\"\u003e\n \u003cp\u003e2,50 (1,0-3,275)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.530884808013354%\" valign=\"top\"\u003e\n \u003cp\u003e0,10\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.5559265442404%\" valign=\"top\"\u003e\n \u003cp\u003eHAS-BLED*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.03839732888147%\" valign=\"top\"\u003e\n \u003cp\u003e2,0 (1,0-2,0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.874791318864773%\" valign=\"top\"\u003e\n \u003cp\u003e2,0 (1,0-2,0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.530884808013354%\" valign=\"top\"\u003e\n \u003cp\u003e0,49\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.5559265442404%\" valign=\"top\"\u003e\n \u003cp\u003eD-dimer (\u0026micro;g/L)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.03839732888147%\" valign=\"top\"\u003e\n \u003cp\u003e4500 (4321-4572)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.874791318864773%\" valign=\"top\"\u003e\n \u003cp\u003e4281 (4249-4336)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.530884808013354%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0,001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.5559265442404%\" valign=\"top\"\u003e\n \u003cp\u003eTroponin (ng/L)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.03839732888147%\" valign=\"top\"\u003e\n \u003cp\u003e55,0 (36,0-133,0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.874791318864773%\" valign=\"top\"\u003e\n \u003cp\u003e62,0 (32,0-99,0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.530884808013354%\" valign=\"top\"\u003e\n \u003cp\u003e0,36\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.5559265442404%\" valign=\"top\"\u003e\n \u003cp\u003eCreatinine (mg/dL)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.03839732888147%\" valign=\"top\"\u003e\n \u003cp\u003e1,0 (0,8-1,21)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.874791318864773%\" valign=\"top\"\u003e\n \u003cp\u003e0,92 (0,77-1,22)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.530884808013354%\" valign=\"top\"\u003e\n \u003cp\u003e0,216\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.5559265442404%\" valign=\"top\"\u003e\n \u003cp\u003eHemoglobin (g/dL), (mean\u0026plusmn;SD)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.03839732888147%\"\u003e\n \u003cp\u003e13,82\u0026plusmn;2,12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.874791318864773%\"\u003e\n \u003cp\u003e12,35\u0026plusmn;2,12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.530884808013354%\"\u003e\n \u003cp\u003e\u003cstrong\u003e0,001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.5559265442404%\" valign=\"top\"\u003e\n \u003cp\u003ePlatelet count (/\u0026micro;L)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.03839732888147%\"\u003e\n \u003cp\u003e218000\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(180000-275000)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.874791318864773%\"\u003e\n \u003cp\u003e236000\u003c/p\u003e\n \u003cp\u003e(194750-306750)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.530884808013354%\"\u003e\n \u003cp\u003e0,21\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e*: median (Iq25-Iq75)\u003c/p\u003e\n\u003cp\u003eAbbreviations: CHF: Congestive Heart Failure, COPD: Chronic Obstructive Pulmonary Disease, CTPA: Computed Thorax Pulmonary Angiography, CVD: Cerebrovascular Disease, IPF: Idiopathic Pulmonary Fibrosis, , SD: Standard Deviation, , sPESI: Simplified Pulmonary Embolism Severity Index.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFigure 2.\u0026nbsp;\u003c/strong\u003eThe distribution of sPESI scores of the cases in the thrombolytic and anticoagulation groups\u003c/p\u003e\n\u003cp\u003eThe comparison of the two groups regarding the PE risk factors showed that immobility was found in 13 (22%) patients in the thrombolytic group. \u0026nbsp;Of these patients, 4 had surgical history and 4 had immobilization due to trauma history. In the anticoagulation group, immobilization was found in 17 (44.7%) patients. Immobilization was observed in 5 patients with surgical history and in 4 patients after trauma. There was a statistically significant difference between the two groups respect to immobility (p=0.013). There was no contraindication for thrombolysis in the patients having history of surgery and trauma. There was no significant difference between the two groups for DVT and travel history.\u003c/p\u003e\n\u003ch3\u003e4.2.2. Patients\u0026rsquo; Vital Signs\u003c/h3\u003e\n\u003cp\u003eThe thrombolytic group and the anticoagulation group were similar in terms of systolic arterial blood pressure, mean arterial blood pressure, PaO\u003csub\u003e2\u003c/sub\u003e/FiO\u003csub\u003e2\u003c/sub\u003e ratio measured before treatment on the admission day. \u0026nbsp;The pulse rate per minute on the admission was higher in the thrombolytic group (Table 2). \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2\u003c/strong\u003e. Vital signs of the thrombolytic and anticoagulation group on the admission day, before treatment\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"585\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"38.6986301369863%\"\u003e\n \u003cp\u003e\u003cstrong\u003eParameters\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.26027397260274%\"\u003e\n \u003cp\u003e\u003cstrong\u003eThrombolytic Group (n=59)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.26027397260274%\"\u003e\n \u003cp\u003e\u003cstrong\u003eAnticoagulation Group (n=38)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.78082191780822%\"\u003e\n \u003cp\u003e\u003cstrong\u003ep value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"38.6986301369863%\"\u003e\n \u003cp\u003eAdmission day systolic BP, \u003cem\u003e(mmHg)\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.26027397260274%\"\u003e\n \u003cp\u003e121 (105-130)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.26027397260274%\"\u003e\n \u003cp\u003e122 (112-140)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.78082191780822%\"\u003e\n \u003cp\u003e0,14\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"38.6986301369863%\"\u003e\n \u003cp\u003eAdmission day mean BP, \u003cem\u003e(mmHg)\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.26027397260274%\"\u003e\n \u003cp\u003e88 (80-100)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.26027397260274%\"\u003e\n \u003cp\u003e89 (85-100)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.78082191780822%\"\u003e\n \u003cp\u003e0,45\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"38.6986301369863%\"\u003e\n \u003cp\u003eAdmission day pulse /min\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.26027397260274%\"\u003e\n \u003cp\u003e116 (105-127)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.26027397260274%\"\u003e\n \u003cp\u003e107 (86-121)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.78082191780822%\"\u003e\n \u003cp\u003e\u003cstrong\u003e0,032\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"38.6986301369863%\"\u003e\n \u003cp\u003eAdmission day\u0026nbsp;PaO\u003csub\u003e2\u003c/sub\u003e/FiO\u003csub\u003e2\u003c/sub\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.26027397260274%\"\u003e\n \u003cp\u003e330 (270-380)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.26027397260274%\"\u003e\n \u003cp\u003e293 (255-389)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.78082191780822%\"\u003e\n \u003cp\u003e0,45\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eAll data are provided as median (Iq25-Iq75).\u003c/p\u003e\n\u003cp\u003eAbbreviations: BP: Blood Pressure, PaO\u003csub\u003e2\u003c/sub\u003e/FiO\u003csub\u003e2\u0026nbsp;\u003c/sub\u003eratio: Arterial Partial Oxygen Pressure/ Fractionated Oxygen ratio.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3.\u0026nbsp;\u003c/strong\u003eEvaluation of the differences in the vital signs of patients in thrombolytic and anticoagulation groups on the\u0026nbsp;admission day and the second day\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"614\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"13.821138211382113%\" valign=\"top\"\u003e\u0026nbsp;\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"43.08943089430894%\" colspan=\"3\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eThrombolytic Group (n=59)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"43.08943089430894%\" colspan=\"3\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eAnticoagulation Group (n=38)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"13.821138211382113%\"\u003e\n \u003cp\u003e\u003cstrong\u003eParameters\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.910569105691057%\"\u003e\n \u003cp\u003e\u003cstrong\u003eAdmission Day\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.447154471544716%\"\u003e\n \u003cp\u003e\u003cstrong\u003eSecond Day\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.731707317073171%\"\u003e\n \u003cp\u003e\u003cstrong\u003ep value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.910569105691057%\"\u003e\n \u003cp\u003e\u003cstrong\u003eAdmission Day\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.284552845528456%\"\u003e\n \u003cp\u003e\u003cstrong\u003eSecond Day\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.894308943089431%\"\u003e\n \u003cp\u003e\u003cstrong\u003ep value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"13.821138211382113%\" valign=\"top\"\u003e\n \u003cp\u003eSystolic BP, \u003cem\u003e(mmHg)\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.910569105691057%\"\u003e\n \u003cp\u003e121 (105-130)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.447154471544716%\"\u003e\n \u003cp\u003e123 (114-132)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.731707317073171%\"\u003e\n \u003cp\u003e0,15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.910569105691057%\"\u003e\n \u003cp\u003e122 (112-140)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.284552845528456%\"\u003e\n \u003cp\u003e128 (111-141)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.894308943089431%\"\u003e\n \u003cp\u003e0,64\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"13.821138211382113%\" valign=\"top\"\u003e\n \u003cp\u003eMean BP, \u003cem\u003e(mmHg)\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.910569105691057%\"\u003e\n \u003cp\u003e88 (80-100)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.447154471544716%\"\u003e\n \u003cp\u003e87 (82-95)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.731707317073171%\"\u003e\n \u003cp\u003e0,82\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.910569105691057%\"\u003e\n \u003cp\u003e89 (85-100)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.284552845528456%\"\u003e\n \u003cp\u003e92 (80-101)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.894308943089431%\"\u003e\n \u003cp\u003e0,63\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"13.821138211382113%\"\u003e\n \u003cp\u003ePulse /min\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.910569105691057%\"\u003e\n \u003cp\u003e116 (105-127)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.447154471544716%\"\u003e\n \u003cp\u003e91 (80-104)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.731707317073171%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0,001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.910569105691057%\"\u003e\n \u003cp\u003e107 (86-121)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.284552845528456%\"\u003e\n \u003cp\u003e94 (80-101)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.894308943089431%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0,001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"13.821138211382113%\"\u003e\n \u003cp\u003ePaO\u003csub\u003e2\u003c/sub\u003e/FiO\u003csub\u003e2\u0026nbsp;\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.910569105691057%\"\u003e\n \u003cp\u003e330 (270-380)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.447154471544716%\"\u003e\n \u003cp\u003e417 (351-447)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.731707317073171%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0,001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.910569105691057%\"\u003e\n \u003cp\u003e293 (255-389)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.284552845528456%\"\u003e\n \u003cp\u003e351 (263-384)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.894308943089431%\"\u003e\n \u003cp\u003e0,27\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eAll data are provided as median (Iq25-Iq75).\u003c/p\u003e\n\u003cp\u003eAbbreviations: BP: Blood Pressure, PaO\u003csub\u003e2\u003c/sub\u003e/FiO\u003csub\u003e2\u0026nbsp;\u003c/sub\u003eratio:\u0026nbsp;Arterial Partial Oxygen Pressure / Fractionated Oxygen ratio.\u003c/p\u003e\n\u003cp\u003eTable 3 presents the changes in the vital signs of each group after treatment. While there were significant improvements in oxygenation (p\u0026lt;0.001) and pulse rates (p\u0026lt;0.001) on the second day in the patients treated with\u0026nbsp;thrombolysis; the decreased pulse rate was observed in the group receiving anticoagulants (p\u0026lt;0.001). There was no significant change in systolic and mean blood pressure measurements in both groups (Table 3).\u003c/p\u003e\n\u003ch3\u003e4.2.3. Comparison of Complications and Mortality\u003c/h3\u003e\n\u003cp\u003eStatistically significant differences were not found in the comparison of complications related to treatment in two groups. No major bleeding was detected. The duration of hospitalization was similar in two groups; while the length of intensive care unit was shorter in the anticoagulation group compared to the thrombolytic group (p \u0026lt;0,001) (Table 4).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 4:\u003c/strong\u003e Complications and complication rates, intensive care and hospitalization times of the thrombolytic and anticoagulation groups\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"604\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"35.9271523178808%\"\u003e\n \u003cp\u003e\u003cstrong\u003eParameters\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.496688741721854%\"\u003e\n \u003cp\u003e\u003cstrong\u003eThrombolytic Group (n=59)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.834437086092716%\"\u003e\n \u003cp\u003e\u003cstrong\u003eAnticoagulation Group (n=38)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.741721854304636%\"\u003e\n \u003cp\u003e\u003cstrong\u003ep value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"35.9271523178808%\" valign=\"top\"\u003e\n \u003cp\u003eComplication present, \u003cem\u003en (%)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.496688741721854%\" valign=\"top\"\u003e\n \u003cp\u003e5 (8,5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.834437086092716%\" valign=\"top\"\u003e\n \u003cp\u003e2 (5,3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.741721854304636%\" valign=\"top\"\u003e\n \u003cp\u003e0,70\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"35.9271523178808%\" valign=\"top\"\u003e\n \u003cp\u003eComplication types\u003c/p\u003e\n \u003cp\u003e-Hematoma\u003c/p\u003e\n \u003cp\u003e-Hematuria\u003c/p\u003e\n \u003cp\u003e-Unexplained hemoglobin drop\u003c/p\u003e\n \u003cp\u003e-Hemoptysis\u003c/p\u003e\n \u003cp\u003e-HIT\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.496688741721854%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1 (1,7)\u003c/p\u003e\n \u003cp\u003e1 (1,7)\u003c/p\u003e\n \u003cp\u003e1 (1,7)\u003c/p\u003e\n \u003cp\u003e2 (3,4)\u003c/p\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.834437086092716%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003cp\u003e1 (2,6)\u003c/p\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003cp\u003e1 (2,6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.741721854304636%\" valign=\"top\"\u003e\u0026nbsp;\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"35.9271523178808%\" valign=\"top\"\u003e\n \u003cp\u003eIn-hospital mortality, \u003cem\u003en (%)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.496688741721854%\" valign=\"top\"\u003e\n \u003cp\u003e4 (6,7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.834437086092716%\" valign=\"top\"\u003e\n \u003cp\u003e5 (13,1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.741721854304636%\" valign=\"top\"\u003e\n \u003cp\u003e0,73\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"35.9271523178808%\" valign=\"top\"\u003e\n \u003cp\u003eDuration of intensive care unit \u003cem\u003e(day)\u003c/em\u003e*\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.496688741721854%\" valign=\"top\"\u003e\n \u003cp\u003e3,0 (2,0-4,0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.834437086092716%\" valign=\"top\"\u003e\n \u003cp\u003e1,5 (0-2,25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.741721854304636%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0,001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"35.9271523178808%\" valign=\"top\"\u003e\n \u003cp\u003eDuration of hospital stay\u003cem\u003e\u0026nbsp;(day)\u003c/em\u003e* \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.496688741721854%\" valign=\"top\"\u003e\n \u003cp\u003e9,0 (6,0-11,0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.834437086092716%\" valign=\"top\"\u003e\n \u003cp\u003e8,0 (6,0-12,0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.741721854304636%\" valign=\"top\"\u003e\n \u003cp\u003e0,69\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e*: median (Iq25-Iq75)\u003c/p\u003e\n\u003cp\u003eAbbreviations: HIT: Heparin Induced Thrombocytopenia.\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe anticoagulant preparation to be used for maintenance treatment was decided by the attending physician. Treatment durations were determined according to the underlying causes. There was no difference between the two groups in terms of CPTE and CTEPH. Of these, 43 patients in the thrombolytic group and 26 patients in the anticoagulation group were followed up regarding CPTE and CTEPH. One-month mortality rate was found to be 6,8% in the half-dose thrombolytic group and 15,8% in the anticoagulation group. Even though mortality ratio was lower in the thrombolytic group, this difference was not statistically significant. Also, one-year mortality rate was found as 13.7% and 26.3% respectively (p=0.17) (Table 5).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 5.\u0026nbsp;\u003c/strong\u003eMortality rates and long-term complications in the thrombolytic group and anticoagulation group\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"604\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"35.76158940397351%\"\u003e\n \u003cp\u003e\u003cstrong\u003eParameters, \u003cem\u003en (%)\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.503311258278146%\"\u003e\n \u003cp\u003e\u003cstrong\u003eThrombolytic Group (n=59)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.503311258278146%\"\u003e\n \u003cp\u003e\u003cstrong\u003eAnticoagulation Group (n=38)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.2317880794702%\"\u003e\n \u003cp\u003e\u003cstrong\u003ep value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"35.76158940397351%\" valign=\"top\"\u003e\n \u003cp\u003eOne \u003cem\u003emonth\u003c/em\u003e mortality\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.503311258278146%\"\u003e\n \u003cp\u003e4/59 (6,7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.503311258278146%\"\u003e\n \u003cp\u003e6/38 (15,8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.2317880794702%\" valign=\"top\"\u003e\n \u003cp\u003e0,18\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"35.76158940397351%\" valign=\"top\"\u003e\n \u003cp\u003eOne \u003cem\u003eyear\u0026nbsp;\u003c/em\u003emortality\u003cem\u003e\u0026nbsp;*\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.503311258278146%\"\u003e\n \u003cp\u003e7/51 (13,7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.503311258278146%\"\u003e\n \u003cp\u003e10/38 (26,3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.2317880794702%\" valign=\"top\"\u003e\n \u003cp\u003e0,17\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"35.76158940397351%\"\u003e\n \u003cp\u003eChronic Pulmonary Thromboembolism **\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.503311258278146%\"\u003e\n \u003cp\u003e4/43 (9,3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.503311258278146%\"\u003e\n \u003cp\u003e1/23 (4,3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.2317880794702%\"\u003e\n \u003cp\u003e0,65\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"35.76158940397351%\"\u003e\n \u003cp\u003eChronic Thromboembolic Pulmonary Hypertension\u003cem\u003e\u0026nbsp;**\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.503311258278146%\"\u003e\n \u003cp\u003e2/43 (4,3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.503311258278146%\"\u003e\n \u003cp\u003e1/23 (4,3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.2317880794702%\"\u003e\n \u003cp\u003e1,0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"35.76158940397351%\"\u003e\n \u003cp\u003eRe-embolism \u003cem\u003e***\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.503311258278146%\"\u003e\n \u003cp\u003e1/46 (2,2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.503311258278146%\"\u003e\n \u003cp\u003e3/32(9,4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.2317880794702%\"\u003e\n \u003cp\u003e0,30\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e* Mortality was evaluated in 51 patients whose follow-up period was completed.\u003c/p\u003e\n\u003cp\u003e** Patients with missing data were not included in this analysis, only 66 patients were assessed.\u003c/p\u003e\n\u003cp\u003e*** Re-embolism: There were 78 patients followed for recurrent embolism.\u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eThis study compared half-dose alteplase and LMWH for initial treatment in patients diagnosed with intermediate-high risk PE. The one-month and one-year mortality rates were found to be lower in the thrombolytic\u0026nbsp;group compared to the anticoagulation group, but these differences were not statistically significant. According to Pulmonary Thromboembolism Guidelines of the European Society of Cardiology/European Respiratory Society, these two pharmacological agents were compared for the first time in the intermediate-high risk PE group, and no significant difference was observed between the groups in terms of major bleeding, minor bleeding, and long-term complications.\u003c/p\u003e\n\u003cp\u003eIntermediate-high risk PE group has a higher mortality risk compared to intermediate-low group because this group has increased risk for developing right ventricle\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003efailure without hemodynamic decompensation. ESC/ERS guideline suggests anticoagulant therapy and close follow-ups in this patient group. The guideline recommends fibrinolytic treatment in case hemodynamic decompensation develops. \u0026nbsp;The American Society of Hematology does not recommend the routine use of thrombolytics in hemodynamically stable patients with right heart failure. The most important reason for not making recommendations in favour of thrombolytics in these guidelines is the lack of sufficient data.\u0026nbsp;(2,11). On the other hand, the use of thrombolytics for intermediate-high risk PE patients is often discussed by \u0026ldquo;Pulmonary Embolism Response Teams\u0026rdquo;\u0026nbsp;(12,13). In our clinical practice, patients in this group are treated with half-dose thrombolytic therapy after the establishment of EGEPET unless contraindicated.\u003c/p\u003e\n\u003cp\u003eIn their study, Mirambeaux et al. followed 1015 hemodynamically stable patients prospectively. According to results, intermediate-high risk PE was found in 97 (9.6%) of the patients based on the ESC/ERS PE guideline. The one-month all-cause mortality in this patient group was 24%\u0026nbsp;(14). In our presented study, mortality rate was 6,7% in the thrombolytic group and 15,8% in the anticoagulation group. However, the contribution of the application of reperfusion therapy to low mortality rate in these series cannot be confirmed because of the limited number of patients.\u003c/p\u003e\n\u003cp\u003eArterial hypotension, tachycardia, low partial oxygen pressure and low oxygen saturation parameters are seen as \u0026nbsp;risk factors for short-term (30-day) mortality in the literature in addition to hemodynamic instability\u0026nbsp;(15,16). Declined blood pressure and PaO\u003csub\u003e2\u003c/sub\u003e/FiO\u003csub\u003e2\u003c/sub\u003e ratio, and increased pulse value are accepted as poor prognosis signs during follow-up. In our study, vital signs of patients were similar in both groups on the admission day; but after half-dose thrombolytic treatment, significant decreases in pulse rate per minute and significant increases in PaO\u003csub\u003e2\u003c/sub\u003e/FiO\u003csub\u003e2\u003c/sub\u003e value were observed, pointing to clinically rapid improvement in the thrombolytic group. But this response did not affect the long-term results.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eBoth thrombolytic therapy and anticoagulation therapy have well-recognized complications. The most common complication for both treatments is bleeding. Meta-analysis made by Zuo et al. has shown that thrombolysis increases major bleeding by 2.84 times and minor bleeding by 2.97 times compared to the anticoagulation\u0026nbsp;(17). Although there is evidence that thrombolytic therapy increases the risk of bleeding, it has also been shown that thrombolytic therapy corrects signs of right ventricle failure more rapidly and effectively\u0026nbsp;(4). In this situation, making a decision to use thrombolytic therapy, which is a risky treatment, becomes an important clinical problem.\u003c/p\u003e\n\u003cp\u003eWhen studies evaluating patient groups similar to the present study are analyzed, different results are observed between thrombolytic and anticoagulation therapy.\u003c/p\u003e\n\u003cp\u003eThe meta-analysis conducted on eleven studies by Riera-Mestre et al. analyzed the efficacy and side-effects of the thrombolytic therapy. It was observed that in these studies, a reduced dose of alteplase was used in seven studies used, Tenecteplase was used in three studies, and urokinase was used in one study. Research results showed that thrombolysis did not reduce mortality risk, but increased bleeding risk by 2.83 times. In addition, it was concluded that thrombolytic therapy increased the risk of intracranial hemorrhage by 2.36 times, although this result was not statistically significant. With these results, the authors do not recommend the use of thrombolytics in intermediate-risk PE\u0026nbsp;(18). In this meta-analysis, the patients were not classified as intermediate-high and intermediate-low risk according to new guidelines. However, there are also other studies reporting that thrombolytic therapy does not increase the risk of bleeding compared to anticoagulation therapy.\u0026nbsp;(19). In the present study, no major bleeding was observed, and no difference was found between the anticoagulant (5.3%) and thrombolytic (8.5%) groups in terms of minor bleeding.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eMeyer et al. investigated Tenecteplase and unfractionated heparin treatments among PE patients with right ventricular failure and elevated troponin. Tenecteplase 30-50 mg was used (the dose used in acute myocardial infarction) as a thrombolytic and compared with the unfractionated heparin treatment group. The primary endpoint of this study was the development of hemodynamic decompensation 7 days after randomization. While hemodynamic decompensation was found to develop in 13 patients (2.6%) in the thrombolytic group, it was observed in 28 patients (5.6%) treated with heparin (p=0.02). \u0026nbsp;However, this result was not significant in the patient subgroups younger than 75. \u0026nbsp;There was important bleeding in the thrombolytic group. In addition, the 30-day mortality rate was 2.4% in the thrombolytic group and 3.2% in the anticoagulation group, and this outcome was not statistically significant\u0026nbsp;(4). Although the case definitions here were similar the present study, the patients having hemodynamic decompensation during follow-up and whose thrombolytic therapy was completed to full dose were excluded in our analysis. And different thrombolytic agents were used in these two studies.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe MOPETT study compared the efficacy of thrombolytic therapy with low-dose tissue plasminogen activator and anticoagulant in patients with intermediate-risk. Heparin infusion or enoxaparin was administered for anticoagulation therapy. In MOPETT trial, intermediate risk PE was defined as clinical findings of PE and the presence of severe radiological PE (more than 70% involvement in more than two lobar arteries in CTPA or presence of involvement in the main pulmonary artery or involvement of more than two lobes in V/P scintigraphy). \u0026nbsp;This definition is different from the intermediate-high risk PE diagnosis in the ESC/ERS guideline which was used in our study. The hospital mortality rate was 1.6% in the thrombolytic group and 5% in the anticoagulation group. While no recurrent embolism occurred in the thrombolytic arm, 5% of the anticoagulation arm had recurrent embolism (p=0.08). No bleeding was observed in both groups. The hospital mortality rate in our study and the frequency of recurrent emboli were higher compared to MOPETT study. Recurrent embolism rate in both studies were lower in the thrombolytic arm than the anticoagulation arm. But these differences were not significant. \u0026nbsp;We have to remember that in the MOPETT study, right ventricle failure and troponin positivity were not assessed, the patients were classed into only radiological findings rather than clinical severity.\u0026nbsp;(20). Moreover, our patient group was older than MOPETT trial group and was evaluated with Charlson Comorbidity Index. In MOPETT, while there was no difference between the groups in terms of the presence of one-to-one comorbidity, the burden of all comorbidities was not seemed to be evaluated.\u003c/p\u003e\n\u003cp\u003eIn T\u0026uuml;rkiye, Yılmaz et al. compared the efficacy of LMWH and 50 mg alteplase in patients with PE who were hemodynamically stable but had right ventricle failure findings in CTPA or ECHO. There were 38 patients in each group. One death (3%) occurred in the thrombolytic group within 30 days, while death was observed in 4 (10%) patients in the anticoagulation group (p=0.36). When the development of hemodynamic decompensation or death in the first 30 days was considered together, hemodynamic decompensation/death was observed in 1 patient in the thrombolytic group and in 10 patients in the anticoagulation group (p=0.009). In other words, one-month mortality was not affected by half-dose alteplase, but the development of hemodynamic decompensation could be prevented. Although similar in design to our study, biomarkers were not used in this study as indicators of cardiac damage\u0026nbsp;(6).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAnalysis of the RIETE database showed that the average length of hospitalization in acute PE decreased from 13.6 days in 2001 to 9.3 days in 2013 (p\u0026lt;0,001). This may be explained by the increased popularity of out-patient follow-up in recent years and more frequent use of LMWH treatment instead of unfractioned heparin\u0026nbsp;(21). In our study, the duration of hospitalization was similar to the literature and there was no difference between the groups, however the duration of intensive care stay was longer in the thrombolytic group. This difference may be due to the fact that nowadays the intermediate-high risk patient group in terms of mortality may switch to the high mortality group within the first 24-48 hours and these patients are followed up in the intensive care unit. In addition, patients given thrombolytics should be followed closely for bleeding. All of these may contribute to the length of hospitalization in the intensive care unit. The historical control group in the present study, which received anticoagulants, were mostly followed up in the ward or had short-term intensive care unit hospitalizations.\u003c/p\u003e\n\u003cp\u003eFindings of right ventricular failure and large thrombus in the pulmonary arteries increase the risk of CTEPH\u0026nbsp;(22). The results of the study following 219 patients with intermediate risk PE presented that 13.2% of patients develop right ventricular dysfunction on ECHO after CTEPH status or post-PE impairment\u0026nbsp;(23). Although thrombolytic therapy is thought to be protective against CPTE or CTEPH, more data are needed on this subject. When the MOPETT study was analyzed in terms of the development of pulmonary hypertension (Systolic Pulmonary Artery Pressure above 40 mmHg on ECHO), the rate of development of pulmonary hypertension during follow-up was 57% in the group receiving anticoagulation and 16% in the group receiving thrombolytics (p\u0026lt;0.001)\u0026nbsp;(20). In the present study, the rates of CPTE or CTEPH were the same between the two groups, but it should be remembered that the follow-up period was longer in patients receiving anticoagulants.\u003c/p\u003e\n\u003cp\u003eIt was observed that thrombolytic therapy was used for intermediate-high risk patients more intensively after the establishment of EGEPET. This study, which aimed to investigate the efficacy of reperfusion therapy with alteplase as half dose, has some limitations. First, this study is single-centered and should be interpreted with caution in terms of generalizing the results. Second, since the number of patients planned at the beginning of the study could not be reached, therefore, the targeted study power could not be achieved. Since the intermediate-high-risk group is less common in acute PE compared to other risk classes, the total number of patients remained at 97 during the seven-year period. Third, the prospectively enrolled thrombolytic case arm was followed up closely, whereas anticoagulant group data were obtained retrospectively from patient records. Patients who received anticoagulation treatment after the establishment of EGEPET were excluded for preventing selection bias. Fourth, this study was not designed as a randomized controlled trial, but the analyses showed that the groups were similar in terms of demographic and clinical findings at admission. Fifth, patients whose hemodynamic deteriorated following reperfusion therapy with half-dose thrombolytics or who received full dose thrombolytics due to increased oxygen demand were excluded. Sixth, the follow up of complications proved to be more difficult due to COVID-19 pandemic, especially in the years 2020-2021. However, we should remember that this is a real-life study.\u0026nbsp;\u003c/p\u003e"},{"header":"CONCLUSION","content":"\u003cp\u003eThe issue of \u0026quot;whether anticoagulants should be used in treatment or reperfusion therapy with thrombolytics\u0026quot; in intermediate-high risk patients with acute PE is still a controversial issue. Guidelines recommend using anticoagulation therapy initially and using thrombolytic therapy if hemodynamic decompensation develops. However, they also point that the level of evidence is not sufficient for this recommendation. In recent years, studies were published describing the experiences of multidisciplinary Pulmonary Embolism Response Teams and initial thrombolytic therapy in hemodynamically stable patients with right ventricle failure. Our study is the first study comparing the efficacy of 50 mg Alteplase and LMWH in the intermediate-high risk group for early mortality as classified by the latest ESC/ERS guideline and concluded that PaO2/FiO2 ratio improved significantly after thrombolytic therapy compared to the anticoagulant group.\u003c/p\u003e\n\u003cp\u003eMajor bleeding did not develop as a complication in both groups. Although one-month and one-year mortality was found to be lower in the thrombolytic group, it did not reach statistical significance. Multicenter, randomized controlled studies are needed in this group of patients who have the risk of transition to the massive embolism group within the first 48 hours.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAuthor Declarations\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u003c/strong\u003e The funding sources had no role in the design and conduct of the study; and also funding sources had no role in the collection, management, analysis, and interpretation of the data. Not any funding sources had used in this manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of Interest Disclosures:\u003c/strong\u003e The authors declare no conflict of interest to declare relevant to the content of this manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and material\u003c/strong\u003e: The data of this article is available and can be shared whenever requested.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCode availability (software application or custom code):\u0026nbsp;\u003c/strong\u003eNot Applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contributions\u003c/strong\u003e: Study concept and design: FB, PKE, \u0026Ouml;SU and ME. Acquisition, analysis, or interpretation of data: PKE, \u0026Ouml;SU, A\u0026Ccedil;, \u0026Ouml;C and ES. Drafting of the manuscript: SB, RS, G\u0026Ccedil;, TY and \u0026Ccedil;E. Critical revision of the manuscript for important intellectual content: \u0026Ouml;SU, PKE, MU, TY and KD. Statistical analysis: PKE, \u0026Ouml;SU. Administrative, technical, or material support: FKA, SN, A\u0026Ccedil;, G\u0026Ccedil; and \u0026Ccedil;E. Study supervision: FB, ME, G\u0026Ccedil;, and RS.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval (include appropriate approvals or waivers\u003c/strong\u003e): The study was approved by the Clinical Research Ethics Committee of Ege University Faculty of Medicine (22-4.3/26) and by Republic of T\u0026uuml;rkiye Ministry of Health, Turkish Medicines and Medical Devices Agency (21-AKD-107).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to participate (include appropriate statements):\u003c/strong\u003e Informed consent of the patients was obtained. We keep the signed informed consent of patients.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication (include appropriate statements):\u003c/strong\u003e Informed consent of the patients was obtained. We keep the signed informed consent of patients.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eRaskob GE, Angchaisuksiri P, Blanco AN, B\u0026uuml;ller H, Gallus A, Hunt BJ et al. Thrombosis: a major contributor to global disease burden. Semin Thromb Hemost [Internet]. 2014 Oct 31 [cited 2022 Oct 23];40(7):724\u0026ndash;35. 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Available from: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://link.springer.com/article/\u003c/span\u003e\u003cspan address=\"https://link.springer.com/article/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s00392-018-1405-1\u003c/span\u003e\u003cspan address=\"10.1007/s00392-018-1405-1\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Acute Right Heart Failure, Anticoagulation, Mortality, Pulmonary Thromboembolism, Thrombolytic","lastPublishedDoi":"10.21203/rs.3.rs-3466076/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3466076/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground and Aim:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eUsing thrombolytics in intermediate-high risk pulmonary embolism (PE) patients or not is a controversial issue. This study aimed to evaluate the efficacy and complications of half-dose alteplase and low molecular weight heparin (LMWH) administration in PE patients with intermediate-high risk.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003eMaterial and Methods\u003c/strong\u003e: The patients diagnosed with intermediate-high risk PE at Ege University Medical Faculty Hospital between 01.01.2016 – 13.02.2023 were included in the study. The patients diagnosed with PE after the establishment of Ege Pulmonary Embolism Team (EGEPET) (2.10.2018) formed the prospective part with the thrombolytic group. The retrospective part-anticoagulation group- included the cases treated with LMWH before EGEPET. Two treatment groups were compared in terms of the one-month mortality and the one-year mortality as primary outcomes.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e No difference was found regarding the age, comorbidities and vital findings between thrombolytic group and anticoagulation group. Only, the pulse value was higher in the thrombolytic group (p=0,032). After the treatment, the PaO\u003csub\u003e2\u003c/sub\u003e/FiO\u003csub\u003e2\u003c/sub\u003e ratio increased significantly, and the pulse rate decreased significantly in the thrombolytic group. Improvement was only seen in the pulse rate in the anticoagulation group. There was no major bleeding in both groups. One-month mortality in thrombolytic group was found in 4 patients (6.7%), while that was observed in 6 patients (15.8%) treated with LMWH (p=0,18).\u0026nbsp; One-year mortality rates were 13.7% and 26.3% respectively (p=0,17).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion:\u003c/strong\u003e PaO\u003csub\u003e2\u003c/sub\u003e/FiO\u003csub\u003e2\u003c/sub\u003e ratio improved significantly and rapidly in patients treated with thrombolysis. Even one-month and one-year mortality rates were reduced in thrombolytic group, but this difference was not found statistically significant.\u003c/p\u003e","manuscriptTitle":"Half Dose Alteplase or Low Molecular Weight Heparin in Pulmonary Embolism with Intermediate-High risk: Real life Study at Tertiary Hospital","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-02-13 19:24:08","doi":"10.21203/rs.3.rs-3466076/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"f67c26a9-4959-4e2a-8b6d-1d66911e90b4","owner":[],"postedDate":"February 13th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-04-14T11:10:07+00:00","versionOfRecord":[],"versionCreatedAt":"2024-02-13 19:24:08","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-3466076","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3466076","identity":"rs-3466076","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}