Clinicians should consider the clinical impact of anticoagulant-related bleeding when deciding on the duration of anticoagulant therapy in patients with venous thromboembolism. To provide reliable estimates of the clinical impact of anticoagulant-related bleeding, defined as the case-fatality rate of major bleeding and the risk for intracranial bleeding. MEDLINE (January 1989 to May 2003), Cochrane Controlled Trial Registry, thromboembolism experts, and reference lists; English-language literature only. Randomized, controlled trials and prospective cohort studies that investigated patients with venous thromboembolism who received oral anticoagulant therapy (target international normalized ratio, 2.0 to 3.0) for at least 3 months and that reported major bleeding and death as primary study outcomes. Two reviewers independently extracted data on the number of anticoagulant-related major and intracranial bleeding episodes and on whether these events were fatal or nonfatal. The authors analyzed 33 studies involving 4374 patient-years of oral anticoagulant therapy. For all patients, the case-fatality rate of major bleeding was 13.4% (95% CI, 9.4% to 17.4%) and the rate of intracranial bleeding was 1.15 per 100 patient-years (CI, 1.14 to 1.16 per 100 patient-years). For patients who received anticoagulant therapy for more than 3 months, the case-fatality rate of major bleeding was 9.1% (CI, 2.5% to 21.7%), and the rate of intracranial bleeding was 0.65 per 100 patient-years (CI, 0.63 to 0.68 per 100 patient-years) after the initial 3 months of anticoagulation. The clinical impact of anticoagulant-related major bleeding in patients with venous thromboembolism is considerable, and clinicians should take this into account when deciding whether to continue long-term oral anticoagulant therapy in an individual patient.

Venous thromboembolism (VTE) is a common preventable cause of mortality in hospitalized medical patients. Despite rigorous randomized trials generating strong recommendations for anticoagulant use to prevent VTE, nearly 40% of medical patients receive inappropriate thromboprophylaxis. Knowledge-translation strategies are needed to bridge this gap. We conducted a 16-week pilot cluster randomized controlled trial (RCT) to determine the proportion of medical patients that were appropriately managed for thromboprophylaxis (according to the American College of Chest Physician guidelines) within 24 hours of admission, through the use of a multicomponent knowledge-translation intervention. Our primary goal was to determine the feasibility of conducting this study on a larger scale. The intervention comprised clinician education, a paper-based VTE risk assessment algorithm, printed physicians’ orders, and audit and feedback sessions. Medical wards at six hospitals (representing clusters) in Ontario, Canada were included; three were randomized to the multicomponent intervention and three to usual care (i.e., no active strategies for thromboprophylaxis in place). Blinding was not used. A total of 2,611 patients (1,154 in the intervention and 1,457 in the control group) were eligible and included in the analysis. This multicomponent intervention did not lead to a significant difference in appropriate VTE prophylaxis rates between intervention and control hospitals (appropriate management rate odds ratio = 0.80; 95% confidence interval: 0.50, 1.28; p = 0.36; intra-class correlation coefficient: 0.022), and thus was not considered feasible. Major barriers to effective knowledge translation were poor attendance by clinical staff at education and feedback sessions, difficulty locating preprinted orders, and lack of involvement by clinical and administrative leaders. We identified several factors that may increase uptake of a VTE prophylaxis strategy, including local champions, support from clinical and administrative leaders, mandatory use, and a simple, clinically relevant risk assessment tool. Hospitals allocated to our multicomponent intervention did not have a higher rate of medical inpatients appropriately managed for thromboprophylaxis than did hospitals that were not allocated to this strategy.

The perioperative management of patients who receive a direct oral anticoagulant (DOAC) for atrial fibrillation (AF) and require elective surgery or procedure is a common clinical scenario for which best practices are uncertain.¹ Each year, 1 in 6 patients with AF, or an estimated 6 million patients worldwide, will require perioperative anticoagulant management.^2,3 When DOAC regimens became available for clinical use in AF, starting in 2010, no studies had been conducted to inform the timing of perioperative DOAC therapy interruption and resumption, whether heparin bridging should be given, and whether preoperative coagulation function testing was needed.⁴ Uncertainty about the perioperative management of DOACs may be associated with unsubstantiated practices and increased harm to patients. Thus, a DOAC therapy interruption interval that is too long may increase the risk for thromboembolism, whereas an interruption interval that is too short may increase the risk for bleeding which, in turn, delays anticoagulant resumption.⁵ Perioperative heparin bridging has been used in DOAC-treated patients,⁶ but this practice does not make pharmacologic sense given the short, 8- to 14-hour DOAC elimination half-lives,⁴ its association with increased bleeding, and its questionable efficacy.^6,7 Preoperative coagulation testing has been suggested to identify patients with an excessive residual anticoagulant level in whom a procedure can be delayed or the DOAC reversed,⁸ but this suggestion is problematic because DOAC-specific coagulation tests are not widely available, reference ranges are lacking, and such testing may not be advantageous for patients.⁹