Cost of incorrect application of antithrombotic prophylaxis prior to invasive procedures

Cost of incorrect application of antithrombotic prophylaxis prior to invasive procedures | 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 Cost of incorrect application of antithrombotic prophylaxis prior to invasive procedures María Victoria Cuevas, Ignacio Martínez-Sancho, Jana Arribas, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.2.13237/v4 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 06 Nov, 2019 Read the published version in BMC Health Services Research → Version 4 posted 4 You are reading this latest preprint version Show more versions Abstract Background We analyze the cost of an incorrect application, by the haematologist, of bridging anticoagulation in patients with low-risk atrial fibrillation (AF) needing interruption of treatment prior to a scheduled invasive procedure. Although not recommended, bridging therapy is widely used, resulting in avoidable costs and increased workload. Methods Observational retrospective study. We recorded demographic and clinical data including age, sex, type of procedure, use of bridging therapy with low molecular weight heparin (LMWH), and haemorrhagic complications within 30 days of acenocoumarol withdrawal. Results Acenocoumarol was stopped in 161 patients, 97 (60%) were male and 64 (40%) female. Average age was 76,11 ± 8,45 years. Procedures included: minor surgical intervention 58 (36%), colonoscopy 61 (38%), gastroscopy 11 (7%), breast biopsy 4 (2.5%), prostate biopsy 4 (2.5%), infiltration 5 (3%), and other 18 (11%). All patients received bridging anticoagulation with LMWH (40mg enoxaparin per day) 3 days before and 3 days after the procedure (6 doses). We used a total of 966 doses, at €4.5 per unit, resulted in €4,347 of total cost. No complications occurred in 156 patients (97%). Haemorrhage was observed in 5 cases: 1 major haemorrhage needing 6 days of hospital stay and transfusion, and 4 minor haemorrhages (2 patients needed emergency attendance and 2 required hospital admission for 3 and 2 days, respectively). The cost of emergency care was €237.36, and the cost of hospital stay was €6860.81 (€623.71 per day, for 11 days). The total cost of the incorrect application of the protocol was €11445.17. Conclusion Guidelines about bridging anticoagulation in low risk AF patients undergoing scheduled invasive procedures were not followed. This practice increments the complications and supposes an increase in costs besides to an inadequate use of the human resources. Health Economics & Outcomes Research Health Policy Atrial fibrillation Bridging therapy Guidelines Avoidable costs Workload. Background Anticoagulation therapy with oral vitamin K antagonists (VKA) is indicated for the prevention of thromboembolic events in patients presenting with atrial fibrillation (AF) (1). Given that embolic and haemorrhagic risks vary among patients, risk stratification scores aimed at identifying candidates for anticoagulation therapy have been proposed (2). The CHADS 2 score (Congestive heart failure, Hypertension, Age, Diabetes mellitus, Stroke) is currently considered a simple and reliable tool (3,4). In Spain, the oral VKA acenocoumarol is preferentially used (5), mainly because its pharmacokinetics seem to be more predictable and allow easier postoperative management compared to warfarin (6). However, anticoagulation needs to be stopped prior to any invasive procedure, and approximately 10% of these patients require treatment discontinuation every year (7). In the perioperative management of these patients, we need to consider the balance between the risk of thromboembolic events and the risk of postoperative haemorrhage. Douketis et al (7) reported that AF patients with a CHADS 2 score of 0 to 2 can be categorized as being at low risk (5% annual risk of thromboembolism after the discontinuation of oral anticoagulation treatment), and bridging anticoagulation is thus not recommended. Scientific societies have provided guidelines for the interruption and re-initiation of oral anticoagulation within the perioperative period (8). Depending on the individual risk, anticoagulation needs to be stopped 3 to 5 days before the procedure, and low molecular weight heparin (LMWH) is generally used for bridging anticoagulation. In recent years, the number of patients receiving anticoagulation therapy has increased with accompanying increases in costs; this is partly attributable to a higher demand from the healthcare workers attending these patients. Healthcare managers should be aware of the challenges posed by anticoagulation therapy in terms of adherence to the established guidelines, which may help better adjust the workload to the personnel (9). The objective of this study was to analyse the complications and costs derived from the use of bridging anticoagulation in low-risk AF patients treated with acenocoumarol undergoing invasive procedures. Materials and Methods This was a 1-year observational retrospective study that included all patients receiving oral anticoagulation therapy and followed by haematologists belonging to the Anticoagulation Unit of the Haematology Department of the University Hospital in Burgos, in collaboration with general practitioners from several primary care centres within the province of Burgos, Spain. We included AF patients scoring 0 to 2 on the CHADS 2 who were treated with acenocoumarol and needed to interrupt the therapy because of a scheduled invasive procedure. Currently, the Anticoagulation Unit of our centre shares responsibility with the primary care physicians and nurses regarding the performance of INR (International Normalized Ratio) tests and the registration of relevant treatment notes in the electronic medical records of these patients. Our electronic resource TAONET® allows the inclusion of any relevant information inside the “Comments” section, such as the need for anticoagulant therapy discontinuation prior to surgery or other invasive procedures. Additionally, the haematologist can prescribe and register the dose of acenocoumarol, specify when to withdraw the treatment and recommend the best way of substituting another anticoagulant. We searched for haemorrhagic complications recorded in the patients’ clinical records that occurred within 30 days of the interruption of oral anticoagulant therapy due to an invasive procedure. Patient demographic and clinical data, the reasons for therapy discontinuation, the type of invasive procedure, the use of bridging anticoagulation, and the types of haemorrhagic complications were recorded and analysed. Laboratory data, including haemoglobin values and the number of units of packed red blood cells transfused, were also recorded. We analysed each occurrence of haemorrhagic complications in terms of emergency unit assessment, the need for hospital admission, the need for transfusion, hospital stay attributable to haemorrhagic complications, and the final outcome. A major haemorrhagic event was defined as a lethal haemorrhage, symptomatic haemorrhage in a critical organ (intracranial, intra-spinal, intra-ocular, retroperitoneal, intra-articular, pericardial, and intramuscular provoking a compartment syndrome), haemoglobin value decrease of more than 20 g/L or the need for the transfusion of 2 or more units of packed red blood cells (10). Non-life-threatening haemorrhages (epistaxis, ecchymosis or haematuria) not needing transfusion were considered minor haemorrhagic events. All clinical data were included in a Microsoft Office Excel 2010 spreadsheet and later exported and analysed with IBM SPSS v.19 software. A descriptive statistical analysis was performed that included the costs of bridging therapy and haemorrhagic complications attributed to LMWH treatment. Results Within the study period, oral acenocoumarol treatment was interrupted prior to a scheduled invasive procedure in 161 AF patients scoring 0 to 2 on CHADS 2 . The average age was 76.1 years (standard deviation, 8.5 years); 64 (40%) were female (average age 77.0 ± 8, 09), and 97 were male (average age 75.5 ± 8.66). Table 1 shows the types of procedures performed. Table 1: Invasive procedures Procedure Patients (n) Patients (%) 161 100% Minor surgical intervention 58 36 Colonoscopy 61 38 Gastroscopy 11 7 Prostate biopsy 4 2,5 Breast biopsy 4 2,5 Infiltration* 5 3 Other procedure** 18 11 *Knee, left saphenous neuropathy, internal anal sphincter, ankle and left femorocutaneous nerve. **salivary gland biopsy, implant of intraocular corticoid delivery device, cystoscopy (5 patients), biopsy of cavum, lung biopsy, thyroid nodule biopsy (3 patients), bronchoscopy, lumbar puncture, endometrial biopsy, pancreatic mass biopsy, renal mass biopsy and sentinel node biopsy. No complications occurred in 156 patients (97%). Five patients (3%) had haemorrhagic complications: 1 had a major haemorrhage, and 4 had minor haemorrhages (Table 2). Table 2. Patients’ clinical features. Variable Female (n/%) Male (n/%) Global (n/%) Sex 64 (40) 97 (60) 161 (100) Age (years) 77. 03 (± 8, 09) 75.51 (± 8,66) 76.11 (± 8.45) Invasive procedure Minor surgical intervention 23 (39.6) 35 (60.4) 58 (36) Colonoscopy 24 (39.3) 37 (60.7) 61(38) Gastroscopy 6 (54.5) 5 (45.5) 11(7) Prostate biopsy 4 (2.5) 4 (2.5) Breast biopsy 4 (2.5) 4 (2.5) Infiltration 0 5 (3) 5 (3) Other procedures 7 (38.8) 11 (61.2) 18 (11) No complications 62 (38.5) 93 (58.5) 156 (96.9) Complications: 2 3 5 (3.1) Major haemorrhage 1 (0.6) 0 1 (0.6) Minor haemorrhage 1 (0.6) 3 (1.8) 4 (2.4) All patients recovered from the haemorrhagic complication without sequelae. All patients received 40 mg per day subcutaneous enoxaparin for 6 days; acenocoumarol was stopped 3 days before the scheduled procedure, and it was re-initiated the same day as the procedure. Bridging anticoagulation was begun 3 days prior to the procedure and maintained for 3 days afterwards, thus overlapping with acenocoumarol. We used 966 doses of enoxaparin for the entire cohort, with a cost of €4.50 per dose, yielding a total cost of €4,347. The cost of attendance at the Emergency Unit was €237.36 (€118.68 per patient), and the cost related to hospital admissions was €6860.81 (€623.71 per day, 11 days). Thus, we estimate the total cost of an incorrect application of antithrombotic prophylaxis to be €11445.17 (Table 3). Table 3. Cost of incorrect application of antithrombotic prophylaxis. Use of LMWH and healthcare resources Euro Total ( € ) Bridging anticoagulation (LMWH) 966 (6 doses/161 patients) 4.5 €/unit 4.347 Emergency Unit 2 patients 118.68 €/ patient 237.36 Hospital Admission 3 patients (11 days) 623.71 € /day 6860.81 Total cost 11445.17 Discussion According to the recommendations provided by the American College of Chest Physicians (ACCP 2012), the thrombotic risk in patients previously receiving treatment with oral anticoagulants who need treatment interruption because of an invasive procedure, is classified into three groups (7). Patients presenting with AF and a CHADS 2 score of 0 to 2 (without a history of stroke or transient ischaemic event) and patients with a history of venous thromboembolism at least 12 months before but no other risk factors belong to the low risk group. However, evidence about the perioperative management of oral VKA is limited and stems from observational studies and recommendations provided by scientific societies (11). In fact, there seems to be a great discrepancy between the opinions of haematologists and primary care physicians regarding the timing and appropriateness of bridging anticoagulation prior to invasive procedures. To clarify this controversy, Douketis et al conducted the BRIDGE study, a double-blind, placebo-controlled randomized trial in which, following the interruption of warfarin therapy prior to an invasive procedure, patients were randomized to receive either bridging anticoagulation with LMWH or a placebo. The objective was to identify the need for bridging anticoagulation in AF patients undergoing invasive procedures. The primary endpoints of the study included the occurrence of arterial thromboembolism and major bleeding episodes within 30 days after the procedure. The study included 1,884 patients: 950 received the placebo, and 934 received bridging anticoagulation. The incidence of thromboembolism was 0.4% and 0.3% in the placebo and treatment groups, respectively, with a risk difference of 0.1 percentage points (95% confidence interval [CI], -0.6 to 0.8; P=0.01 for noninferiority). However, the rates of major haemorrhagic episodes were 1.3% and 3.2% in the placebo and treatment groups, respectively (relative risk, 0.41; 95% CI, 0.20 to 0.78; P=0.005 for superiority). The authors concluded that patients who received bridging therapy had not only similar rates of thromboembolic complications but also fewer major bleeding episodes (12). In our study, in which bridging anticoagulation was used in all patients, we observed incidence rates of 0.62% and 2.4% for major and minor bleeding events, respectively. The misuse of bridging anticoagulation by haematologists and primary care physicians is a matter of concern among scientific societies, and these societies have questioned this practice. Moreover, the Canadian Haematology Society has suggested that bridging anticoagulation should not be offered to patients unless the risk of thrombosis clearly outweighs the risk of haemorrhage, given that the majority of patients will likely not benefit and that it might result in unwanted complications, increasing the cost and avoidable work overload (14). The study by Rios et al. has shown that, in AF patients receiving VKA treatment, bridging anticoagulation prior to an invasive procedure was independently associated with a higher risk of all peri-procedure complications (15). In Spain, the use of warfarin is relatively low (5.2%), and we lack specific data regarding bridging anticoagulation. However, the management of non-valvular AF patients receiving acenocoumarol does not seem to be different from the management of patients receiving warfarin, and data are generalizable (16). An increasing number of patients receiving VKA necessarily means more personnel working in Anticoagulation Units. In our area, the management and control of oral anticoagulation therapy has been decentralized and shared with general practitioners using a telemedicine system. This system enhances communication between haematologists and primary care physicians, reduces costs attributed to specialized consultations, and improves patient satisfaction (17,18). This decentralization process granted new competencies to primary care physicians, who have demonstrated good quality management of this therapy (19,20). In our centre, the use of electronic clinical records allows us to issue recommendations about the withdrawal of anticoagulation, so the patient can undergo bridging anticoagulation as an outpatient treatment, thus avoiding a hospital stay, as also reported by Pappas et al (21). However, costs do increase whenever anticoagulation withdrawal and bridging therapy are unnecessarily offered to patients. Given that the cost of controlling oral anticoagulation therapy is lower in primary care than in specialized consultation (22), it seems reasonable that recommendations about anticoagulation withdrawal prior to invasive procedures should ideally be issued by primary care physicians, thus reducing specialist workload. We believe that primary care physicians should be involved in the implementation of oral anticoagulation guidelines. A close observation of such guidelines should result not only in fewer adverse effects and complications but also in reduced costs (23). In our centre, we have been using unnecessary bridging therapy with LMWH, which has resulted in cases of post-procedure haemorrhage. This practice has increased costs because of emergency attendance and hospital stays for the management of haemorrhagic complications. In Europe, such a discrepancy between the recommendations in the guidelines and clinical practice has led to the design of electronic resources aimed to help with the correct application of protocols and to enhance adherence to the guidelines (24). Conclusions An incorrect application of the guidelines may increase the risk of haemorrhage, so efforts should be made to update local procedures according to international recommendations. Subsequently, the implementation of protocols based on such recommendations requires periodic analysis and follow-up to ensure correct adherence and better control and rationalization of costs and personnel workload. Abbreviations VKA: Vitamin K antagonists AF: Atrial fibrillation LMWH: Low molecular weight heparin CHADS2: Congestive heart failure, Hypertension, Age, Diabetes mellitus, Stroke INR: International Normalized Ratio CEIm: Drug Research Ethics Committee ACCP: American College of Chest Physicians Declarations ETHICS APPROVAL AND CONSENT TO PARTICIPATE The conduction of this study was approved by the local Ethics Committee (Ref. 1550 CEIm (Drug Research Ethics Committee of Burgos and Soria) being asked for informed consent to patients. The data used in this study are closed and an administrative permission to access and use of them was received from the local Ethics Committee. CONSENT FOR PUBLICATION Not applicable AVAILABILITY OF DATA AND MATERIAL All data generated or analysed during this study are included in this published article The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request. COMPETING INTERESTS The authors declare that they have no competing interests. FUNDING This work was supported by the Fundación Burgos por la Investigación de la Salud. The Fundación Burgos por la Investigación de la Salud did not participate in the design, in the collection, analysis or interpretation of the data or in the writing of the manuscript. AUTHORS' CONTRIBUTIONS M.V.C., I.M-S., J.A., C. G-D and B.C. have participated in the desing, data collection and analysis of the results. All authors read and approved the final manuscript ACKNOWLEDGEMENT Not applicable References 1- Petersen P , Boysen G , Godtfredsen J , Andersen ED , Andersen B . Placebo-controlled, randomised trial of warfarin and aspirin for prevention of thromboembolic complications in chronic atrial fibrillation. The Copenhagen AFASAK study. Lancet. 1989; 1(8631): 175-79. 2- Brandes A, Overgaard M, Plauborg L, Dehlendorff C, Lyck F, Peulicke J, Poulsen SV, Husted S.(2013). 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Efficacy and safety of peri-procedural bridging therapy with low molecular weight heparin in atrial fibrillation patients under vitamin K antagonists. QJM. 2019; 112(3): 183-88. 16- Barrios V , Escobar C , Prieto L , Lobos JM , Polo J , Vargas D . Control of Anticoagulation With Warfarin or Acenocoumarol in Spain. Do They Differ?. Rev Esp Cardiol (Engl Ed). 2015; 68 (12): 1181-82. 17- Testa S , Alatri A , Paoletti O , Morstabilini G , Medagliani MA , Denti N , Martellenghi E . Reorganisation of an anticoagulation clinic using a telemedicine system: description of the model and preliminary results. Intern Emerg Med. 2006; 1(1): 24-29. 18- Horner K , Wagner E , Tufano J . Electronic consultations between primary and specialty care clinicians: early insights. Issue Brief (Commonw Fund). 2011; 23: 1-14. 19- Alonso Roca R , Figueroa Guerrero CA , Mainar de Paz V , Arribas García MP , Sánchez Perruca L , Rodríguez Barrientos R , Casado López M , Pedraza Flechas AM . Quality control of oral anticoagulant therapy in Primary Care in Madrid City, Spain: CHRONOS-TAO study. Med Clin (Barc). 2015; 145(5): 192-97. 20- Liu S , Singer A , McAlister FA , Peeler W , Heran BS , Drummond N , Manca DP , Allan GM , Korownyk C , Kolber MR , Greiver M , Garrison SR . Quality of warfarin management in primary care: Determining the stability of international normalized ratios using a nationally representative prospective cohort. Can Fam Physician. 2019; 65(6): 416-25. 21- Pappas MA , Barnes GD , Vijan S . Cost-Effectiveness of Bridging Anticoagulation Among Patients with Nonvalvular Atrial Fibrillation. J Gen Intern Med. 2019; 34(4): 583-90. 22- Parry D , Bryan S , Gee K , Murray E , Fitzmaurice D . Patient costs in anticoagulation management: a comparison of primary and secondary care. Br J Gen Pract. 2001; 51(473): 972-76. 23- Pelkofski EB , Baker WD , Rowlingson JC , Cantrell LA , Duska LR . Quality Initiative to Improve Compliance With Perioperative Anticoagulation. J Oncol Pract. 2019; doi: 10.1200/JOP.18.00748. 24- Deharo JC , Sciaraffia E , Leclercq C et al. Coordinated by the Scientific Initiatives Committee of the European Heart Rhythm Association Perioperative management of antithrombotic treatment during implantation or revision of cardiac implantable electronic devices: the European Snapshot Survey on Procedural Routines for Electronic Device Implantation (ESS-PREDI). Europace. 2016; 18(5): 778-84. Cite Share Download PDF Status: Published Journal Publication published 06 Nov, 2019 Read the published version in BMC Health Services Research → Version 4 posted Submission checks completed at journal 07 Nov, 2019 Editorial decision: Accept 21 Oct, 2019 Editor assigned by journal 20 Oct, 2019 Editor invited by journal 19 Oct, 2019 You are reading this latest preprint version Show more versions Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-3951","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research article","associatedPublications":[],"authors":[{"id":220781,"identity":"c5d9dcd7-8710-4db8-8cee-1a12b9a80660","order_by":1,"name":"María Victoria Cuevas","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAsklEQVRIiWNgGAWjYDADfgkGNhK1SM4gWYvBDWK16M5Ifibxsc3O3vh2j9ljHgYbe4JazG6kmUnObEtO3HbnjLkxD0NaYgNBLWfOsEnznGFOMLuRYybNw3A4gbAtIC1/ztTbG88Aa/lPhMOO97BJM1QcZtwgAdZygJGww463GVv2VBxPnHEjrdxwjkEyEX45zPzwxg+Danv+GcnbHrypsCPsMDRgQKqGUTAKRsEoGAVYAQBdkzYcey/aUAAAAABJRU5ErkJggg==","orcid":"https://orcid.org/0000-0001-7991-1234","institution":"Hospital Universitario de Burgos","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"María","middleName":"Victoria","lastName":"Cuevas","suffix":""},{"id":220782,"identity":"c0e5ce7a-898d-42a1-adab-9a2297141612","order_by":2,"name":"Ignacio Martínez-Sancho","email":"","orcid":"","institution":"Primary Care Centre \"Gamonal-Antigua\"","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Ignacio","middleName":"","lastName":"Martínez-Sancho","suffix":""},{"id":220783,"identity":"c8b8aaca-f613-4ca9-bb2c-54231740e64f","order_by":3,"name":"Jana Arribas","email":"","orcid":"","institution":"Hospital Universitario de Burgos","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Jana","middleName":"","lastName":"Arribas","suffix":""},{"id":220784,"identity":"70c30744-3ae9-49d2-9afb-088b36e3fa22","order_by":4,"name":"Covadonga García-Díaz","email":"","orcid":"","institution":"Hospital Universitario de Burgos","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Covadonga","middleName":"","lastName":"García-Díaz","suffix":""},{"id":220785,"identity":"1b186941-38dd-49df-a3d6-b9efd5a7d77f","order_by":5,"name":"Beatriz Cuevas","email":"","orcid":"","institution":"Hospital Universitario de Burgos","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Beatriz","middleName":"","lastName":"Cuevas","suffix":""}],"badges":[],"createdAt":"2019-08-16 14:17:09","currentVersionCode":4,"declarations":"","doi":"10.21203/rs.2.13237/v4","doiUrl":"https://doi.org/10.21203/rs.2.13237/v4","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12913-019-4669-x","type":"published","date":"2019-11-06T12:00:00+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":13479078,"identity":"285c50a7-80d9-4a77-b4a1-7615be7f4329","added_by":"auto","created_at":"2021-09-16 21:37:51","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":221893,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3951/v4/3b89ddde-6f95-4ad1-91b8-25a46457b4a7.pdf"}],"financialInterests":"","formattedTitle":"Cost of incorrect application of antithrombotic prophylaxis prior to invasive procedures","fulltext":[{"header":"Background","content":"\u003cp\u003eAnticoagulation therapy with oral vitamin K antagonists (VKA) is indicated for the prevention of thromboembolic events in patients presenting with atrial fibrillation (AF) (1).\u003c/p\u003e\n\u003cp\u003eGiven that embolic and haemorrhagic risks vary among patients, risk stratification scores aimed at identifying candidates for anticoagulation therapy have been proposed (2). The CHADS\u003csub\u003e2\u003c/sub\u003e score (Congestive heart failure, Hypertension, Age, Diabetes mellitus, Stroke) is currently considered a simple and reliable tool (3,4).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn Spain, the oral VKA acenocoumarol is preferentially used (5), mainly because its pharmacokinetics seem to be more predictable and allow easier postoperative management compared to warfarin (6).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eHowever, anticoagulation needs to be stopped prior to any invasive procedure, and approximately 10% of these patients require treatment discontinuation every year (7).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn the perioperative management of these patients, we need to consider the balance between the risk of thromboembolic events and the risk of postoperative haemorrhage.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eDouketis et al (7) reported that AF patients with a CHADS\u003csub\u003e2\u003c/sub\u003e score of 0 to 2 can be categorized as being at low risk (5% annual risk of thromboembolism after the discontinuation of oral anticoagulation treatment), and bridging anticoagulation is thus not recommended.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eScientific societies have provided guidelines for the interruption and re-initiation of oral anticoagulation within the perioperative period (8). Depending on the individual risk, anticoagulation needs to be stopped 3 to 5 days before the procedure, and low molecular weight heparin (LMWH) is generally used for bridging anticoagulation.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn recent years, the number of patients receiving anticoagulation therapy has increased with accompanying increases in costs; this is partly attributable to a higher demand from the healthcare workers attending these patients.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eHealthcare managers should be aware of the challenges posed by anticoagulation therapy in terms of adherence to the established guidelines, which may help better adjust the workload to the personnel (9).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe objective of this study was to analyse the complications and costs derived from the use of bridging anticoagulation in low-risk AF patients treated with acenocoumarol undergoing invasive procedures.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cp\u003eThis was a 1-year observational retrospective study that included all patients receiving oral anticoagulation therapy and followed by haematologists belonging to the Anticoagulation Unit of the Haematology Department of the University Hospital in Burgos, in collaboration with general practitioners from several primary care centres within the province of Burgos, Spain.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eWe included AF patients scoring 0 to 2 on the CHADS\u003csub\u003e2\u003c/sub\u003e who were treated with acenocoumarol and needed to interrupt the therapy because of a scheduled invasive procedure. Currently, the Anticoagulation Unit of our centre shares responsibility with the primary care physicians and nurses regarding the performance of INR (International Normalized Ratio) tests and the registration of relevant treatment notes in the electronic medical records of these patients.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eOur electronic resource TAONET\u0026reg; allows the inclusion of any relevant information inside the \u0026ldquo;Comments\u0026rdquo; section, such as the need for anticoagulant therapy discontinuation prior to surgery or other invasive procedures. Additionally, the haematologist can prescribe and register the dose of acenocoumarol, specify when to withdraw the treatment and recommend the best way of substituting another anticoagulant.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eWe searched for haemorrhagic complications recorded in the patients\u0026rsquo; clinical records that occurred within 30 days of the interruption of oral anticoagulant therapy due to an invasive procedure.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ePatient demographic and clinical data, the reasons for therapy discontinuation, the type of invasive procedure, the use of bridging anticoagulation, and the types of haemorrhagic complications were recorded and analysed. Laboratory data, including haemoglobin values and the number of units of packed red blood cells transfused, were also recorded.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eWe analysed each occurrence of haemorrhagic complications in terms of emergency unit assessment, the need for hospital admission, the need for transfusion, hospital stay attributable to haemorrhagic complications, and the final outcome.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eA major haemorrhagic event was defined as a lethal haemorrhage, symptomatic haemorrhage in a critical organ (intracranial, intra-spinal, intra-ocular, retroperitoneal, intra-articular, pericardial, and intramuscular provoking a compartment syndrome), haemoglobin value decrease of more than 20 g/L or the need for the transfusion of 2 or more units of packed red blood cells (10). Non-life-threatening haemorrhages (epistaxis, ecchymosis or haematuria) not needing transfusion were considered minor haemorrhagic events.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAll clinical data were included in a Microsoft Office Excel 2010 spreadsheet and later exported and analysed with IBM SPSS v.19 software. A descriptive statistical analysis was performed that included the costs of bridging therapy and haemorrhagic complications attributed to LMWH treatment.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eWithin the study period, oral acenocoumarol treatment was interrupted prior to a scheduled invasive procedure in 161 AF patients scoring 0 to 2 on CHADS\u003csub\u003e2\u003c/sub\u003e. The average age was 76.1 years (standard deviation, 8.5 years); 64 (40%) were female (average age 77.0 \u0026plusmn; 8, 09), and 97 were male (average age 75.5 \u0026plusmn; 8.66). Table 1 shows the types of procedures performed.\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 150%; font-family: 'Times New Roman',serif;\"\u003eTable 1: Invasive procedures\u003c/span\u003e\u003c/p\u003e\n\u003ctable style=\"border-collapse: collapse; border: none;\"\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 92.15pt; border: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"123\"\u003e\n\u003cp style=\"margin-bottom: .0001pt; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 150%; font-family: 'Times New Roman',serif;\"\u003eProcedure\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 92.1pt; border: solid windowtext 1.0pt; border-left: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"123\"\u003e\n\u003cp style=\"margin-bottom: .0001pt; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 150%; font-family: 'Times New Roman',serif;\"\u003ePatients (n)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 92.15pt; border: solid windowtext 1.0pt; border-left: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"123\"\u003e\n\u003cp style=\"margin-bottom: .0001pt; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 150%; font-family: 'Times New Roman',serif;\"\u003ePatients (%)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 92.15pt; border: solid windowtext 1.0pt; border-top: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"123\"\u003e\n\u003cp style=\"margin-bottom: .0001pt; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 150%; font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 92.1pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"123\"\u003e\n\u003cp style=\"margin-bottom: .0001pt; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 150%; font-family: 'Times New Roman',serif;\"\u003e161\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 92.15pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"123\"\u003e\n\u003cp style=\"margin-bottom: .0001pt; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 150%; font-family: 'Times New Roman',serif;\"\u003e100%\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 92.15pt; border: solid windowtext 1.0pt; border-top: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"123\"\u003e\n\u003cp style=\"margin-bottom: .0001pt; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 150%; font-family: 'Times New Roman',serif;\"\u003eMinor surgical intervention\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 92.1pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"123\"\u003e\n\u003cp style=\"margin-bottom: .0001pt; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 150%; font-family: 'Times New Roman',serif;\"\u003e58\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 92.15pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"123\"\u003e\n\u003cp style=\"margin-bottom: .0001pt; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 150%; font-family: 'Times New Roman',serif;\"\u003e36\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 92.15pt; border: solid windowtext 1.0pt; border-top: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"123\"\u003e\n\u003cp style=\"margin-bottom: .0001pt; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 150%; font-family: 'Times New Roman',serif;\"\u003eColonoscopy\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 92.1pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"123\"\u003e\n\u003cp style=\"margin-bottom: .0001pt; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 150%; font-family: 'Times New Roman',serif;\"\u003e61\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 92.15pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"123\"\u003e\n\u003cp style=\"margin-bottom: .0001pt; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 150%; font-family: 'Times New Roman',serif;\"\u003e38\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 92.15pt; border: solid windowtext 1.0pt; border-top: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"123\"\u003e\n\u003cp style=\"margin-bottom: .0001pt; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 150%; font-family: 'Times New Roman',serif;\"\u003eGastroscopy\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 92.1pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"123\"\u003e\n\u003cp style=\"margin-bottom: .0001pt; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 150%; font-family: 'Times New Roman',serif;\"\u003e11\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 92.15pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"123\"\u003e\n\u003cp style=\"margin-bottom: .0001pt; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 150%; font-family: 'Times New Roman',serif;\"\u003e7\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 92.15pt; border: solid windowtext 1.0pt; border-top: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"123\"\u003e\n\u003cp style=\"margin-bottom: .0001pt; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 150%; font-family: 'Times New Roman',serif;\"\u003eProstate biopsy\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 92.1pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"123\"\u003e\n\u003cp style=\"margin-bottom: .0001pt; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 150%; font-family: 'Times New Roman',serif;\"\u003e4\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 92.15pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"123\"\u003e\n\u003cp style=\"margin-bottom: .0001pt; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 150%; font-family: 'Times New Roman',serif;\"\u003e2,5\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 92.15pt; border: solid windowtext 1.0pt; border-top: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"123\"\u003e\n\u003cp style=\"margin-bottom: .0001pt; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 150%; font-family: 'Times New Roman',serif;\"\u003eBreast biopsy\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 92.1pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"123\"\u003e\n\u003cp style=\"margin-bottom: .0001pt; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 150%; font-family: 'Times New Roman',serif;\"\u003e4\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 92.15pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"123\"\u003e\n\u003cp style=\"margin-bottom: .0001pt; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 150%; font-family: 'Times New Roman',serif;\"\u003e2,5\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 92.15pt; border: solid windowtext 1.0pt; border-top: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"123\"\u003e\n\u003cp style=\"margin-bottom: .0001pt; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 150%; font-family: 'Times New Roman',serif;\"\u003eInfiltration*\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 92.1pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"123\"\u003e\n\u003cp style=\"margin-bottom: .0001pt; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 150%; font-family: 'Times New Roman',serif;\"\u003e5\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 92.15pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"123\"\u003e\n\u003cp style=\"margin-bottom: .0001pt; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 150%; font-family: 'Times New Roman',serif;\"\u003e3\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 92.15pt; border: solid windowtext 1.0pt; border-top: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"123\"\u003e\n\u003cp style=\"margin-bottom: .0001pt; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 150%; font-family: 'Times New Roman',serif;\"\u003eOther procedure**\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 92.1pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"123\"\u003e\n\u003cp style=\"margin-bottom: .0001pt; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 150%; font-family: 'Times New Roman',serif;\"\u003e18\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 92.15pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"123\"\u003e\n\u003cp style=\"margin-bottom: .0001pt; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 150%; font-family: 'Times New Roman',serif;\"\u003e11\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 150%; font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 200%; font-family: 'Times New Roman',serif;\"\u003e*Knee, left saphenous neuropathy, internal anal sphincter, ankle and left femorocutaneous nerve.\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 200%; font-family: 'Times New Roman',serif;\"\u003e**salivary gland biopsy, implant of intraocular corticoid delivery device, cystoscopy (5 patients), biopsy of cavum, lung biopsy, thyroid nodule biopsy (3 patients), bronchoscopy, lumbar puncture, endometrial biopsy, pancreatic mass biopsy, renal mass biopsy and sentinel node biopsy.\u003c/span\u003e\u003c/p\u003e\u003c/br\u003e\u003c/br\u003e\n\u003cp\u003eNo complications occurred in 156 patients (97%). Five patients (3%) had haemorrhagic complications: 1 had a major haemorrhage, and 4 had minor haemorrhages (Table 2).\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 150%; font-family: 'Times New Roman',serif;\"\u003eTable 2. \u003c/span\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 150%; font-family: 'Times New Roman',serif;\"\u003ePatients\u0026rsquo;\u003c/span\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 150%; font-family: 'Times New Roman',serif;\"\u003e clinical features.\u003c/span\u003e\u003c/p\u003e\n\u003ctable style=\"border-collapse: collapse; border: none;\"\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 108.05pt; border: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"144\"\u003e\n\u003cp style=\"margin-bottom: .0001pt; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 150%; font-family: 'Times New Roman',serif;\"\u003eVariable\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 108.05pt; border: solid windowtext 1.0pt; border-left: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"144\"\u003e\n\u003cp style=\"margin-bottom: .0001pt; text-align: center; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 150%; font-family: 'Times New Roman',serif;\"\u003eFemale (n/%)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 108.05pt; border: solid windowtext 1.0pt; border-left: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"144\"\u003e\n\u003cp style=\"margin-bottom: .0001pt; text-align: center; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 150%; font-family: 'Times New Roman',serif;\"\u003eMale (n/%)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 108.05pt; border: solid windowtext 1.0pt; border-left: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"144\"\u003e\n\u003cp style=\"margin-bottom: .0001pt; text-align: center; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 150%; font-family: 'Times New Roman',serif;\"\u003eGlobal (n/%)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 108.05pt; border: solid windowtext 1.0pt; border-top: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"144\"\u003e\n\u003cp style=\"margin-bottom: .0001pt; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 150%; font-family: 'Times New Roman',serif;\"\u003eSex\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"margin-bottom: .0001pt; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 150%; font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 108.05pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"144\"\u003e\n\u003cp style=\"margin-bottom: .0001pt; text-align: center; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 150%; font-family: 'Times New Roman',serif;\"\u003e64 (40)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 108.05pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"144\"\u003e\n\u003cp style=\"margin-bottom: .0001pt; text-align: center; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 150%; font-family: 'Times New Roman',serif;\"\u003e97 (60)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 108.05pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"144\"\u003e\n\u003cp style=\"margin-bottom: .0001pt; text-align: center; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 150%; font-family: 'Times New Roman',serif;\"\u003e161 (100)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 108.05pt; border: solid windowtext 1.0pt; border-top: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"144\"\u003e\n\u003cp style=\"margin-bottom: .0001pt; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 150%; font-family: 'Times New Roman',serif;\"\u003eAge (years)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 108.05pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"144\"\u003e\n\u003cp style=\"margin-bottom: .0001pt; text-align: center; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 150%; font-family: 'Times New Roman',serif;\"\u003e77. 03 (\u0026plusmn; 8, 09)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 108.05pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"144\"\u003e\n\u003cp style=\"margin-bottom: .0001pt; text-align: center; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 150%; font-family: 'Times New Roman',serif;\"\u003e75.51 (\u0026plusmn; 8,66)\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"margin-bottom: .0001pt; text-align: center; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 150%; font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 108.05pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"144\"\u003e\n\u003cp style=\"margin-bottom: .0001pt; text-align: center; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 150%; font-family: 'Times New Roman',serif;\"\u003e76.11\u0026nbsp; (\u0026plusmn; 8.45)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 108.05pt; border: solid windowtext 1.0pt; border-top: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"144\"\u003e\n\u003cp style=\"margin-bottom: .0001pt; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 150%; font-family: 'Times New Roman',serif;\"\u003eInvasive procedure \u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 108.05pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"144\"\u003e\n\u003cp style=\"margin-bottom: .0001pt; text-align: center; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 150%; font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 108.05pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"144\"\u003e\n\u003cp style=\"margin-bottom: .0001pt; text-align: center; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 150%; font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 108.05pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"144\"\u003e\n\u003cp style=\"margin-bottom: .0001pt; text-align: center; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 150%; font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 108.05pt; border: solid windowtext 1.0pt; border-top: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"144\"\u003e\n\u003cp style=\"margin-bottom: .0001pt; text-align: right; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 150%; font-family: 'Times New Roman',serif;\"\u003eMinor surgical intervention\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 108.05pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"144\"\u003e\n\u003cp style=\"margin-bottom: .0001pt; text-align: center; line-height: 150%; tab-stops: center 48.6pt;\"\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 150%; font-family: 'Times New Roman',serif;\"\u003e23 (39.6)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 108.05pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"144\"\u003e\n\u003cp style=\"margin-bottom: .0001pt; text-align: center; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 150%; font-family: 'Times New Roman',serif;\"\u003e35 (60.4)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 108.05pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"144\"\u003e\n\u003cp style=\"margin-bottom: .0001pt; text-align: center; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 150%; font-family: 'Times New Roman',serif;\"\u003e58 (36)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 108.05pt; border: solid windowtext 1.0pt; border-top: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"144\"\u003e\n\u003cp style=\"margin-bottom: .0001pt; text-align: right; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 150%; font-family: 'Times New Roman',serif;\"\u003eColonoscopy\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 108.05pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"144\"\u003e\n\u003cp style=\"margin-bottom: .0001pt; text-align: center; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 150%; font-family: 'Times New Roman',serif;\"\u003e24 (39.3)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 108.05pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"144\"\u003e\n\u003cp style=\"margin-bottom: .0001pt; text-align: center; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 150%; font-family: 'Times New Roman',serif;\"\u003e37 (60.7)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 108.05pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"144\"\u003e\n\u003cp style=\"margin-bottom: .0001pt; text-align: center; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 150%; font-family: 'Times New Roman',serif;\"\u003e61(38)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 108.05pt; border: solid windowtext 1.0pt; border-top: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"144\"\u003e\n\u003cp style=\"margin-bottom: .0001pt; text-align: right; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 150%; font-family: 'Times New Roman',serif;\"\u003eGastroscopy\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 108.05pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"144\"\u003e\n\u003cp style=\"margin-bottom: .0001pt; text-align: center; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 150%; font-family: 'Times New Roman',serif;\"\u003e6 (54.5)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 108.05pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"144\"\u003e\n\u003cp style=\"margin-bottom: .0001pt; text-align: center; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 150%; font-family: 'Times New Roman',serif;\"\u003e5 (45.5)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 108.05pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"144\"\u003e\n\u003cp style=\"margin-bottom: .0001pt; text-align: center; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 150%; font-family: 'Times New Roman',serif;\"\u003e11(7)\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"margin-bottom: .0001pt; text-align: center; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 150%; font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 108.05pt; border: solid windowtext 1.0pt; border-top: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"144\"\u003e\n\u003cp style=\"margin-bottom: .0001pt; text-align: right; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 150%; font-family: 'Times New Roman',serif;\"\u003eProstate biopsy\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 108.05pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"144\"\u003e\n\u003cp style=\"margin-bottom: .0001pt; text-align: center; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 150%; font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 108.05pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"144\"\u003e\n\u003cp style=\"margin-bottom: .0001pt; text-align: center; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 150%; font-family: 'Times New Roman',serif;\"\u003e4 (2.5)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 108.05pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"144\"\u003e\n\u003cp style=\"margin-bottom: .0001pt; text-align: center; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 150%; font-family: 'Times New Roman',serif;\"\u003e4 (2.5)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 108.05pt; border: solid windowtext 1.0pt; border-top: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"144\"\u003e\n\u003cp style=\"margin-bottom: .0001pt; text-align: right; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 150%; font-family: 'Times New Roman',serif;\"\u003eBreast biopsy\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 108.05pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"144\"\u003e\n\u003cp style=\"margin-bottom: .0001pt; text-align: center; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 150%; font-family: 'Times New Roman',serif;\"\u003e4 (2.5)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 108.05pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"144\"\u003e\n\u003cp style=\"margin-bottom: .0001pt; text-align: center; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 150%; font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 108.05pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"144\"\u003e\n\u003cp style=\"margin-bottom: .0001pt; text-align: center; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 150%; font-family: 'Times New Roman',serif;\"\u003e4 (2.5)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 108.05pt; border: solid windowtext 1.0pt; border-top: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"144\"\u003e\n\u003cp style=\"margin-bottom: .0001pt; text-align: right; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 150%; font-family: 'Times New Roman',serif;\"\u003eInfiltration\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 108.05pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"144\"\u003e\n\u003cp style=\"margin-bottom: .0001pt; text-align: center; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 150%; font-family: 'Times New Roman',serif;\"\u003e0\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 108.05pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"144\"\u003e\n\u003cp style=\"margin-bottom: .0001pt; text-align: center; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 150%; font-family: 'Times New Roman',serif;\"\u003e5 (3)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 108.05pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"144\"\u003e\n\u003cp style=\"margin-bottom: .0001pt; text-align: center; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 150%; font-family: 'Times New Roman',serif;\"\u003e5 (3)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 108.05pt; border: solid windowtext 1.0pt; border-top: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"144\"\u003e\n\u003cp style=\"margin-bottom: .0001pt; text-align: right; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 150%; font-family: 'Times New Roman',serif;\"\u003eOther procedures\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 108.05pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"144\"\u003e\n\u003cp style=\"margin-bottom: .0001pt; text-align: center; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 150%; font-family: 'Times New Roman',serif;\"\u003e7 (38.8)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 108.05pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"144\"\u003e\n\u003cp style=\"margin-bottom: .0001pt; text-align: center; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 150%; font-family: 'Times New Roman',serif;\"\u003e11 (61.2)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 108.05pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"144\"\u003e\n\u003cp style=\"margin-bottom: .0001pt; text-align: center; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 150%; font-family: 'Times New Roman',serif;\"\u003e18 (11)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 108.05pt; border: solid windowtext 1.0pt; border-top: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"144\"\u003e\n\u003cp style=\"margin-bottom: .0001pt; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 150%; font-family: 'Times New Roman',serif;\"\u003eNo complications\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 108.05pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"144\"\u003e\n\u003cp style=\"margin-bottom: .0001pt; text-align: center; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 150%; font-family: 'Times New Roman',serif;\"\u003e62 (38.5)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 108.05pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"144\"\u003e\n\u003cp style=\"margin-bottom: .0001pt; text-align: center; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 150%; font-family: 'Times New Roman',serif;\"\u003e93 (58.5)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 108.05pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"144\"\u003e\n\u003cp style=\"margin-bottom: .0001pt; text-align: center; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 150%; font-family: 'Times New Roman',serif;\"\u003e156 (96.9)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 108.05pt; border: solid windowtext 1.0pt; border-top: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"144\"\u003e\n\u003cp style=\"margin-bottom: .0001pt; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 150%; font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"margin-bottom: .0001pt; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 150%; font-family: 'Times New Roman',serif;\"\u003eComplications: \u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 108.05pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"144\"\u003e\n\u003cp style=\"margin-bottom: .0001pt; text-align: center; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 150%; font-family: 'Times New Roman',serif;\"\u003e2\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 108.05pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"144\"\u003e\n\u003cp style=\"margin-bottom: .0001pt; text-align: center; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 150%; font-family: 'Times New Roman',serif;\"\u003e3\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 108.05pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"144\"\u003e\n\u003cp style=\"margin-bottom: .0001pt; text-align: center; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 150%; font-family: 'Times New Roman',serif;\"\u003e5 (3.1)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 108.05pt; border: solid windowtext 1.0pt; border-top: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"144\"\u003e\n\u003cp style=\"margin-bottom: .0001pt; text-align: right; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 150%; font-family: 'Times New Roman',serif;\"\u003eMajor haemorrhage\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 108.05pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"144\"\u003e\n\u003cp style=\"margin-bottom: .0001pt; text-align: center; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 150%; font-family: 'Times New Roman',serif;\"\u003e1 (0.6)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 108.05pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"144\"\u003e\n\u003cp style=\"margin-bottom: .0001pt; text-align: center; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 150%; font-family: 'Times New Roman',serif;\"\u003e0\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 108.05pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"144\"\u003e\n\u003cp style=\"margin-bottom: .0001pt; text-align: center; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 150%; font-family: 'Times New Roman',serif;\"\u003e1 (0.6)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 108.05pt; border: solid windowtext 1.0pt; border-top: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"144\"\u003e\n\u003cp style=\"margin-bottom: .0001pt; text-align: right; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 150%; font-family: 'Times New Roman',serif;\"\u003eMinor haemorrhage\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 108.05pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"144\"\u003e\n\u003cp style=\"margin-bottom: .0001pt; text-align: center; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 150%; font-family: 'Times New Roman',serif;\"\u003e1 (0.6)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 108.05pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"144\"\u003e\n\u003cp style=\"margin-bottom: .0001pt; text-align: center; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 150%; font-family: 'Times New Roman',serif;\"\u003e3 (1.8)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 108.05pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"144\"\u003e\n\u003cp style=\"margin-bottom: .0001pt; text-align: center; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 150%; font-family: 'Times New Roman',serif;\"\u003e4 (2.4)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\u003c/br\u003e\u003c/br\u003e\n\u003cp\u003eAll patients recovered from the haemorrhagic complication without sequelae. All patients received 40 mg per day subcutaneous enoxaparin for 6 days; acenocoumarol was stopped 3 days before the scheduled procedure, and it was re-initiated the same day as the procedure.\u003c/p\u003e\n\u003cp\u003eBridging anticoagulation was begun 3 days prior to the procedure and maintained for 3 days afterwards, thus overlapping with acenocoumarol.\u003c/p\u003e\n\u003cp\u003eWe used 966 doses of enoxaparin for the entire cohort, with a cost of \u0026euro;4.50 per dose, yielding a total cost of \u0026euro;4,347.\u003c/p\u003e\n\u003cp\u003eThe cost of attendance at the Emergency Unit was \u0026euro;237.36 (\u0026euro;118.68 per patient), and the cost related to hospital admissions was \u0026euro;6860.81 (\u0026euro;623.71 per day, 11 days). Thus, we estimate the total cost of an incorrect application of antithrombotic prophylaxis to be \u0026euro;11445.17 (Table 3).\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 150%; font-family: 'Times New Roman',serif;\"\u003eTable 3. Cost of incorrect application of antithrombotic prophylaxis.\u003c/span\u003e\u003c/p\u003e\n\u003ctable style=\"border-collapse: collapse; border: none;\"\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 108.05pt; border: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"144\"\u003e\n\u003cp style=\"margin-bottom: .0001pt; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 150%; font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 108.05pt; border: solid windowtext 1.0pt; border-left: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"144\"\u003e\n\u003cp style=\"margin-bottom: .0001pt; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 150%; font-family: 'Times New Roman',serif;\"\u003eUse of LMWH and healthcare resources\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 108.05pt; border: solid windowtext 1.0pt; border-left: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"144\"\u003e\n\u003cp style=\"margin-bottom: .0001pt; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 150%; font-family: 'Times New Roman',serif;\"\u003eEuro\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 108.05pt; border: solid windowtext 1.0pt; border-left: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"144\"\u003e\n\u003cp style=\"margin-bottom: .0001pt; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 150%; font-family: 'Times New Roman',serif;\"\u003eTotal (\u003cspan style=\"color: black;\"\u003e\u0026euro;\u003c/span\u003e)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 108.05pt; border: solid windowtext 1.0pt; border-top: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"144\"\u003e\n\u003cp style=\"margin-bottom: .0001pt; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 150%; font-family: 'Times New Roman',serif;\"\u003eBridging anticoagulation\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"margin-bottom: .0001pt; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 150%; font-family: 'Times New Roman',serif;\"\u003e(LMWH)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 108.05pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"144\"\u003e\n\u003cp style=\"margin-bottom: .0001pt; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: black;\"\u003e966 (6 doses/161 patients)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 108.05pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"144\"\u003e\n\u003cp style=\"margin-bottom: .0001pt; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: black;\"\u003e4.5 \u0026euro;/unit\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 108.05pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"144\"\u003e\n\u003cp style=\"margin-bottom: .0001pt; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: black;\"\u003e4.347\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 108.05pt; border: solid windowtext 1.0pt; border-top: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"144\"\u003e\n\u003cp style=\"margin-bottom: .0001pt; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 150%; font-family: 'Times New Roman',serif;\"\u003eEmergency Unit\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 108.05pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"144\"\u003e\n\u003cp style=\"margin-bottom: .0001pt; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 150%; font-family: 'Times New Roman',serif;\"\u003e2 patients\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 108.05pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"144\"\u003e\n\u003cp style=\"margin-bottom: .0001pt; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: black;\"\u003e118.68 \u0026euro;/ patient\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 108.05pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"144\"\u003e\n\u003cp style=\"margin-bottom: .0001pt; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: black;\"\u003e237.36\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 108.05pt; border: solid windowtext 1.0pt; border-top: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"144\"\u003e\n\u003cp style=\"margin-bottom: .0001pt; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 150%; font-family: 'Times New Roman',serif;\"\u003eHospital Admission\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 108.05pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"144\"\u003e\n\u003cp style=\"margin-bottom: .0001pt; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 150%; font-family: 'Times New Roman',serif;\"\u003e3 patients (11 days)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 108.05pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"144\"\u003e\n\u003cp style=\"margin-bottom: .0001pt; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: black;\"\u003e623.71 \u003c/span\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: black;\"\u003e\u0026euro;\u003c/span\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: black;\"\u003e/day\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 108.05pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"144\"\u003e\n\u003cp style=\"margin-bottom: .0001pt; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: black;\"\u003e6860.81\u0026nbsp; \u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 108.05pt; border: solid windowtext 1.0pt; border-top: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"144\"\u003e\n\u003cp style=\"margin-bottom: .0001pt; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 150%; font-family: 'Times New Roman',serif;\"\u003eTotal cost\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 108.05pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"144\"\u003e\n\u003cp style=\"margin-bottom: .0001pt; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 150%; font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 108.05pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"144\"\u003e\n\u003cp style=\"margin-bottom: .0001pt; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 150%; font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 108.05pt; border-top: none; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"144\"\u003e\n\u003cp style=\"margin-bottom: .0001pt; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 150%; font-family: 'Times New Roman',serif;\"\u003e11445.17 \u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"margin-bottom: .0001pt; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 150%; font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e"},{"header":"Discussion","content":"\u003cp\u003eAccording to the recommendations provided by the American College of Chest Physicians (ACCP 2012), the thrombotic risk in patients previously receiving treatment with oral anticoagulants who need treatment interruption because of an invasive procedure, is classified into three groups (7). Patients presenting with AF and a CHADS\u003csub\u003e2\u003c/sub\u003e score of 0 to 2 (without a history of stroke or transient ischaemic event) and patients with a history of venous thromboembolism at least 12 months before but no other risk factors belong to the low risk group. However, evidence about the perioperative management of oral VKA is limited and stems from observational studies and recommendations provided by scientific societies (11). In fact, there seems to be a great discrepancy between the opinions of haematologists and primary care physicians regarding the timing and appropriateness of bridging anticoagulation prior to invasive procedures.\u003c/p\u003e\n\u003cp\u003eTo clarify this controversy, Douketis et al conducted the BRIDGE study, a double-blind, placebo-controlled randomized trial in which, following the interruption of warfarin therapy prior to an invasive procedure, patients were randomized to receive either bridging anticoagulation with LMWH or a placebo. The objective was to identify the need for bridging anticoagulation in AF patients undergoing invasive procedures. The primary endpoints of the study included the occurrence of arterial thromboembolism and major bleeding episodes within 30 days after the procedure.\u003c/p\u003e\n\u003cp\u003eThe study included 1,884 patients: 950 received the placebo, and 934 received bridging anticoagulation. The incidence of thromboembolism was 0.4% and 0.3% in the placebo and treatment groups, respectively, with a risk difference of 0.1 percentage points (95% confidence interval [CI], -0.6 to 0.8; P=0.01 for noninferiority). However, the rates of major haemorrhagic episodes were 1.3% and 3.2% in the placebo and treatment groups, respectively (relative risk, 0.41; 95% CI, 0.20 to 0.78; P=0.005 for superiority). The authors concluded that patients who received bridging therapy had not only similar rates of thromboembolic complications but also fewer major bleeding episodes (12).\u003c/p\u003e\n\u003cp\u003eIn our study, in which bridging anticoagulation was used in all patients, we observed incidence rates of 0.62% and 2.4% for major and minor bleeding events, respectively.\u003c/p\u003e\n\u003cp\u003eThe misuse of bridging anticoagulation by haematologists and primary care physicians is a matter of concern among scientific societies, and these societies have questioned this practice. Moreover, the Canadian Haematology Society has suggested that bridging anticoagulation should not be offered to patients unless the risk of thrombosis clearly outweighs the risk of haemorrhage, given that the majority of patients will likely not benefit and that it might result in unwanted complications, increasing the cost and avoidable work overload (14).\u003c/p\u003e\n\u003cp\u003eThe study by Rios et al. has shown that, in AF patients receiving VKA treatment, bridging anticoagulation prior to an invasive procedure was independently associated with a higher risk of all peri-procedure complications (15).\u003c/p\u003e\n\u003cp\u003eIn Spain, the use of warfarin is relatively low (5.2%), and we lack specific data regarding bridging anticoagulation. However, the management of non-valvular AF patients receiving acenocoumarol does not seem to be different from the management of patients receiving warfarin, and data are generalizable (16).\u003c/p\u003e\n\u003cp\u003eAn increasing number of patients receiving VKA necessarily means more personnel working in Anticoagulation Units. In our area, the management and control of oral anticoagulation therapy has been decentralized and shared with general practitioners using a telemedicine system.\u003c/p\u003e\n\u003cp\u003eThis system enhances communication between haematologists and primary care physicians, reduces costs attributed to specialized consultations, and improves patient satisfaction (17,18). This decentralization process granted new competencies to primary care physicians, who have demonstrated good quality management of this therapy (19,20). In our centre, the use of electronic clinical records allows us to issue recommendations about the withdrawal of anticoagulation, so the patient can undergo bridging anticoagulation as an outpatient treatment, thus avoiding a hospital stay, as also reported by Pappas et al (21). However, costs do increase whenever anticoagulation withdrawal and bridging therapy are unnecessarily offered to patients. Given that the cost of controlling oral anticoagulation therapy is lower in primary care than in specialized consultation (22), it seems reasonable that recommendations about anticoagulation withdrawal prior to invasive procedures should ideally be issued by primary care physicians, thus reducing specialist workload. We believe that primary care physicians should be involved in the implementation of oral anticoagulation guidelines. A close observation of such guidelines should result not only in fewer adverse effects and complications but also in reduced costs (23).\u003c/p\u003e\n\u003cp\u003eIn our centre, we have been using unnecessary bridging therapy with LMWH, which has resulted in cases of post-procedure haemorrhage. This practice has increased costs because of emergency attendance and hospital stays for the management of haemorrhagic complications. In Europe, such a discrepancy between the recommendations in the guidelines and clinical practice has led to the design of electronic resources aimed to help with the correct application of protocols and to enhance adherence to the guidelines (24).\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eAn incorrect application of the guidelines may increase the risk of haemorrhage, so efforts should be made to update local procedures according to international recommendations. Subsequently, the implementation of protocols based on such recommendations requires periodic analysis and follow-up to ensure correct adherence and better control and rationalization of costs and personnel workload.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eVKA:\u0026nbsp; Vitamin K antagonists\u003c/p\u003e\n\u003cp\u003eAF: Atrial fibrillation\u003c/p\u003e\n\u003cp\u003eLMWH: Low molecular weight heparin\u003c/p\u003e\n\u003cp\u003eCHADS2: Congestive heart failure, Hypertension, Age, Diabetes mellitus, Stroke\u003c/p\u003e\n\u003cp\u003eINR: International Normalized Ratio\u003c/p\u003e\n\u003cp\u003eCEIm: Drug Research Ethics Committee\u003c/p\u003e\n\u003cp\u003eACCP: American College of Chest Physicians\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eETHICS APPROVAL AND CONSENT TO PARTICIPATE\u003c/p\u003e\n\u003cp\u003eThe conduction of this study was approved by the local Ethics Committee (Ref. 1550\u0026nbsp; CEIm (Drug Research Ethics Committee of Burgos and Soria)\u0026nbsp; being asked for informed consent to patients.\u003c/p\u003e\n\u003cp\u003eThe data used in this study are closed and an administrative permission to access and use of them was received from the local Ethics Committee.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eCONSENT FOR PUBLICATION\u003c/p\u003e\n\u003cp\u003eNot applicable\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAVAILABILITY OF DATA AND MATERIAL\u003c/p\u003e\n\u003cp\u003eAll data generated or analysed during this study are included in this published article\u003c/p\u003e\n\u003cp\u003eThe datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eCOMPETING INTERESTS\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003eFUNDING\u003c/p\u003e\n\u003cp\u003eThis work was supported by the Fundaci\u0026oacute;n Burgos por la Investigaci\u0026oacute;n de la Salud.\u003c/p\u003e\n\u003cp\u003eThe Fundaci\u0026oacute;n Burgos por la Investigaci\u0026oacute;n de la Salud did not participate in the design, in the collection, analysis or interpretation of the data or in the writing of the manuscript.\u003c/p\u003e\n\u003cp\u003eAUTHORS' CONTRIBUTIONS\u003c/p\u003e\n\u003cp\u003eM.V.C., I.M-S., J.A., C. G-D and B.C. have participated in the desing, data collection and analysis of the results. All authors read and approved the final manuscript\u003c/p\u003e\n\u003cp\u003eACKNOWLEDGEMENT\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e"},{"header":"References","content":"\u003cp\u003e1-\u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/?term=Petersen%20P%5BAuthor%5D\u0026amp;cauthor=true\u0026amp;cauthor_uid=2563096\"\u003ePetersen P\u003c/a\u003e, \u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/?term=Boysen%20G%5BAuthor%5D\u0026amp;cauthor=true\u0026amp;cauthor_uid=2563096\"\u003eBoysen G\u003c/a\u003e, \u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/?term=Godtfredsen%20J%5BAuthor%5D\u0026amp;cauthor=true\u0026amp;cauthor_uid=2563096\"\u003eGodtfredsen J\u003c/a\u003e, \u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/?term=Andersen%20ED%5BAuthor%5D\u0026amp;cauthor=true\u0026amp;cauthor_uid=2563096\"\u003eAndersen ED\u003c/a\u003e, \u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/?term=Andersen%20B%5BAuthor%5D\u0026amp;cauthor=true\u0026amp;cauthor_uid=2563096\"\u003eAndersen B\u003c/a\u003e. 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Quality control of oral anticoagulant therapy in Primary Care in Madrid City, Spain: CHRONOS-TAO study. \u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/25433789\"\u003eMed Clin (Barc).\u003c/a\u003e 2015; 145(5): 192-97.\u003c/p\u003e\n\u003cp\u003e20- \u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/?term=Liu%20S%5BAuthor%5D\u0026amp;cauthor=true\u0026amp;cauthor_uid=31189630\"\u003eLiu S\u003c/a\u003e, \u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/?term=Singer%20A%5BAuthor%5D\u0026amp;cauthor=true\u0026amp;cauthor_uid=31189630\"\u003eSinger A\u003c/a\u003e, \u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/?term=McAlister%20FA%5BAuthor%5D\u0026amp;cauthor=true\u0026amp;cauthor_uid=31189630\"\u003eMcAlister FA\u003c/a\u003e, \u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/?term=Peeler%20W%5BAuthor%5D\u0026amp;cauthor=true\u0026amp;cauthor_uid=31189630\"\u003ePeeler W\u003c/a\u003e, \u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/?term=Heran%20BS%5BAuthor%5D\u0026amp;cauthor=true\u0026amp;cauthor_uid=31189630\"\u003eHeran BS\u003c/a\u003e, \u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/?term=Drummond%20N%5BAuthor%5D\u0026amp;cauthor=true\u0026amp;cauthor_uid=31189630\"\u003eDrummond N\u003c/a\u003e, \u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/?term=Manca%20DP%5BAuthor%5D\u0026amp;cauthor=true\u0026amp;cauthor_uid=31189630\"\u003eManca DP\u003c/a\u003e, \u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/?term=Allan%20GM%5BAuthor%5D\u0026amp;cauthor=true\u0026amp;cauthor_uid=31189630\"\u003eAllan GM\u003c/a\u003e, \u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/?term=Korownyk%20C%5BAuthor%5D\u0026amp;cauthor=true\u0026amp;cauthor_uid=31189630\"\u003eKorownyk C\u003c/a\u003e, \u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/?term=Kolber%20MR%5BAuthor%5D\u0026amp;cauthor=true\u0026amp;cauthor_uid=31189630\"\u003eKolber MR\u003c/a\u003e, \u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/?term=Greiver%20M%5BAuthor%5D\u0026amp;cauthor=true\u0026amp;cauthor_uid=31189630\"\u003eGreiver M\u003c/a\u003e, \u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/?term=Garrison%20SR%5BAuthor%5D\u0026amp;cauthor=true\u0026amp;cauthor_uid=31189630\"\u003eGarrison SR\u003c/a\u003e. Quality of warfarin management in primary care: Determining the stability of international normalized ratios using a nationally representative prospective cohort. \u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/31189630\"\u003eCan Fam Physician.\u003c/a\u003e 2019; 65(6): 416-25.\u003c/p\u003e\n\u003cp\u003e21-\u0026nbsp; \u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/?term=Pappas%20MA%5BAuthor%5D\u0026amp;cauthor=true\u0026amp;cauthor_uid=30623388\"\u003ePappas MA\u003c/a\u003e, \u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/?term=Barnes%20GD%5BAuthor%5D\u0026amp;cauthor=true\u0026amp;cauthor_uid=30623388\"\u003eBarnes GD\u003c/a\u003e, \u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/?term=Vijan%20S%5BAuthor%5D\u0026amp;cauthor=true\u0026amp;cauthor_uid=30623388\"\u003eVijan S\u003c/a\u003e. Cost-Effectiveness of Bridging Anticoagulation Among Patients with Nonvalvular Atrial Fibrillation. \u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/30623388\"\u003eJ Gen Intern Med.\u003c/a\u003e 2019; 34(4): 583-90.\u003c/p\u003e\n\u003cp\u003e22- \u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/?term=Parry%20D%5BAuthor%5D\u0026amp;cauthor=true\u0026amp;cauthor_uid=11766869\"\u003eParry D\u003c/a\u003e, \u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/?term=Bryan%20S%5BAuthor%5D\u0026amp;cauthor=true\u0026amp;cauthor_uid=11766869\"\u003eBryan S\u003c/a\u003e, \u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/?term=Gee%20K%5BAuthor%5D\u0026amp;cauthor=true\u0026amp;cauthor_uid=11766869\"\u003eGee K\u003c/a\u003e, \u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/?term=Murray%20E%5BAuthor%5D\u0026amp;cauthor=true\u0026amp;cauthor_uid=11766869\"\u003eMurray E\u003c/a\u003e, \u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/?term=Fitzmaurice%20D%5BAuthor%5D\u0026amp;cauthor=true\u0026amp;cauthor_uid=11766869\"\u003eFitzmaurice D\u003c/a\u003e. Patient costs in anticoagulation management: a comparison of primary and secondary care. \u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/11766869\"\u003eBr J Gen Pract.\u003c/a\u003e 2001; 51(473): 972-76.\u003c/p\u003e\n\u003cp\u003e23- \u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/?term=Pelkofski%20EB%5BAuthor%5D\u0026amp;cauthor=true\u0026amp;cauthor_uid=31206339\"\u003ePelkofski EB\u003c/a\u003e, \u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/?term=Baker%20WD%5BAuthor%5D\u0026amp;cauthor=true\u0026amp;cauthor_uid=31206339\"\u003eBaker WD\u003c/a\u003e, \u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/?term=Rowlingson%20JC%5BAuthor%5D\u0026amp;cauthor=true\u0026amp;cauthor_uid=31206339\"\u003eRowlingson JC\u003c/a\u003e, \u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/?term=Cantrell%20LA%5BAuthor%5D\u0026amp;cauthor=true\u0026amp;cauthor_uid=31206339\"\u003eCantrell LA\u003c/a\u003e, \u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/?term=Duska%20LR%5BAuthor%5D\u0026amp;cauthor=true\u0026amp;cauthor_uid=31206339\"\u003eDuska LR\u003c/a\u003e. Quality Initiative to Improve Compliance With Perioperative Anticoagulation. \u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/31206339\"\u003eJ Oncol Pract.\u003c/a\u003e 2019; doi: 10.1200/JOP.18.00748.\u003c/p\u003e\n\u003cp\u003e24- \u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/?term=Deharo%20JC%5BAuthor%5D\u0026amp;cauthor=true\u0026amp;cauthor_uid=27226497\"\u003eDeharo JC\u003c/a\u003e, \u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/?term=Sciaraffia%20E%5BAuthor%5D\u0026amp;cauthor=true\u0026amp;cauthor_uid=27226497\"\u003eSciaraffia E\u003c/a\u003e, \u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/?term=Leclercq%20C%5BAuthor%5D\u0026amp;cauthor=true\u0026amp;cauthor_uid=27226497\"\u003eLeclercq C\u003c/a\u003e et al. \u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/?term=Coordinated%20by%20the%20Scientific%20Initiatives%20Committee%20of%20the%20European%20Heart%20Rhythm%20Association%5BCorporate%20Author%5D\"\u003eCoordinated by the Scientific Initiatives Committee of the European Heart Rhythm Association\u003c/a\u003e Perioperative management of antithrombotic treatment during implantation or revision of cardiac implantable electronic devices: the European Snapshot Survey on Procedural Routines for Electronic Device Implantation (ESS-PREDI). \u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/27226497\"\u003eEuropace.\u003c/a\u003e 2016; 18(5): 778-84.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-health-services-research","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bhsr","sideBox":"Learn more about [BMC Health Services Research](http://bmchealthservres.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/BHSR/default.aspx","title":"BMC Health Services Research","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Atrial fibrillation; Bridging therapy; Guidelines; Avoidable costs; Workload.","lastPublishedDoi":"10.21203/rs.2.13237/v4","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.2.13237/v4","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"Background\n\nWe analyze the cost of an incorrect application, by the haematologist, of bridging anticoagulation in patients with low-risk atrial fibrillation (AF) needing interruption of treatment prior to a scheduled invasive procedure. Although not recommended, bridging therapy is widely used, resulting in avoidable costs and increased workload.\n\nMethods\n\nObservational retrospective study. We recorded demographic and clinical data including age, sex, type of procedure, use of bridging therapy with low molecular weight heparin (LMWH), and haemorrhagic complications within 30 days of acenocoumarol withdrawal.\n\nResults\n\nAcenocoumarol was stopped in 161 patients, 97 (60%) were male and 64 (40%) female. Average age was 76,11 ± 8,45 years. Procedures included: minor surgical intervention 58 (36%), colonoscopy 61 (38%), gastroscopy 11 (7%), breast biopsy 4 (2.5%), prostate biopsy 4 (2.5%), infiltration 5 (3%), and other 18 (11%). All patients received bridging anticoagulation with LMWH (40mg enoxaparin per day) 3 days before and 3 days after the procedure (6 doses). We used a total of 966 doses, at €4.5 per unit, resulted in €4,347 of total cost. No complications occurred in 156 patients (97%). Haemorrhage was observed in 5 cases: 1 major haemorrhage needing 6 days of hospital stay and transfusion, and 4 minor haemorrhages (2 patients needed emergency attendance and 2 required hospital admission for 3 and 2 days, respectively). The cost of emergency care was €237.36, and the cost of hospital stay was €6860.81 (€623.71 per day, for 11 days). The total cost of the incorrect application of the protocol was €11445.17.\n\nConclusion\n\nGuidelines about bridging anticoagulation in low risk AF patients undergoing scheduled invasive procedures were not followed. This practice increments the complications and supposes an increase in costs besides to an inadequate use of the human resources.","manuscriptTitle":"Cost of incorrect application of antithrombotic prophylaxis prior to invasive procedures","msid":"","msnumber":"","nonDraftVersions":[{"code":4,"date":"2019-11-18 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