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Unlabelled: ESSENTIALS: Anticoagulants need to be stopped preprocedure so there is little or no remaining anticoagulant effect. We assessed the residual anticoagulant effect with standardized interruption for patients on dabigatran. With this protocol, 80-86% of patients had no residual anticoagulant effect at the time of a procedure. A standardized perioperative dabigatran protocol appears to be safe, but requires further study., Background: In patients taking dabigatran who require treatment interruption for a surgery/procedure, a sufficient interruption interval is needed so that there is little or no residual anticoagulant effect at the time of the surgery/procedure., Methods: A prospective cohort study of patients receiving dabigatran (110 mg or 150 mg twice daily) who required an elective surgery/procedure and received a standardized dabigatran interruption protocol based on surgery/procedure bleeding risk and renal function was performed. Before the surgery/procedure, a blood sample was taken for measurement of the prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), and dilute thrombin time (dTT). We determined the proportion of all patients and those having a high bleeding risk surgery/procedure with normal coagulation test results at the time of the surgery/procedure. The APTT and dTT were considered to be most likely to reflect a dabigatran anticoagulant effect. Patients were followed up for 30 days postprocedure to assess for bleeding and thromboembolism., Results: One hundred and eighty-one patients were studied: 118 with low bleeding risk, and 63 with high bleeding risk. For all patients, the proportions with normal PT, APTT, TT dTT levels were 92.8%, 79.6%, 33.1%, and 80.7%, respectively. In patients with high bleeding risk, the proportions with normal PT, APTT, TT dTT levels were 93.7%, 85.7%, 57.1%, and 87.3%, respectively. During follow-up, there was one (0.6%) major bleed, there were nine (5.0%) minor bleeds, and there was one (0.6%) transient ischemic attack., Conclusions: In patients receiving dabigatran who require an elective surgery/procedure, a standardized interruption protocol yielded 80-86% of patients with no residual anticoagulant effect at the time of surgery/procedure, and with a low incidence of bleeding., (© 2015 International Society on Thrombosis and Haemostasis.)

Background: Compression ultrasonography is the mainstay of diagnosis of deep-vein thrombosis (DVT) of the legs. Compression ultrasonography can be extended to the entire deep venous system (whole-leg) or restricted to the proximal veins only (limited), and the two approaches are clinically equivalent. We aimed to assess the diagnostic value of an algorithm combining whole-leg and limited compression ultrasonography., Methods: We did a prospective, multicentre, cohort study at eight centres in five countries. Consecutive outpatients aged 18 years or older with suspected DVT underwent D-dimer measurement and pretest clinical probability assessment. DVT was ruled out without further testing if pretest probability was unlikely and D-dimer was negative (group 1). Patients in whom either pretest probability was likely or who were positive for D-dimer underwent limited compression ultrasonography only (group 2). Finally, patients in whom pretest probability was likely and who had a positive measurement for D-dimer underwent extended whole-leg compression ultrasonography (group 3). All patients in whom DVT was ruled out were followed up for 3 months. The primary outcome was the incidence of objectively recorded venous thromboembolism. The primary analysis included all patients managed according to the study protocol. This study is registered with ClinicalTrials.gov, number NCT01412242. The final results are reported here., Findings: Between March 1, 2011, and July 31, 2014, 1348 consecutive outpatients were referred for this study, of whom 1162 were eligible to participate. After pretest probability assessment and D-dimer testing, 351 were in group 1, 401 in group 2, and 410 in group 3. Limited compression ultrasonography was positive in 12 (3%) patients in group 2 and extended whole-leg compression ultrasonography was positive in 200 (49%) patients in group 3. 82 (39%) of all DVT diagnosed at baseline were isolated distal thromboses. 26 protocol violations were reported. Thus, 351 patients from group 1, 371 patients in group 2, and 202 patients in group 3 who had been excluded for DVT by the algorithm were included in the primary analysis at 3 months. One, four, and three DVTs were reported, respectively. Thus, the 3-month incidence of venous thromboembolism in untreated patients after a negative diagnostic strategy was 0·87% (95% CI 0·44-1·70)., Interpretation: An algorithm combining limited and whole-leg compression ultrasonography could be a reliable, safe, and convenient method for diagnostic management of outpatients with clinically suspected DVT., Funding: None., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: It is uncertain whether bridging anticoagulation is necessary for patients with atrial fibrillation who need an interruption in warfarin treatment for an elective operation or other elective invasive procedure. We hypothesized that forgoing bridging anticoagulation would be noninferior to bridging with low-molecular-weight heparin for the prevention of perioperative arterial thromboembolism and would be superior to bridging with respect to major bleeding., Methods: We performed a randomized, double-blind, placebo-controlled trial in which, after perioperative interruption of warfarin therapy, patients were randomly assigned to receive bridging anticoagulation therapy with low-molecular-weight heparin (100 IU of dalteparin per kilogram of body weight) or matching placebo administered subcutaneously twice daily, from 3 days before the procedure until 24 hours before the procedure and then for 5 to 10 days after the procedure. Warfarin treatment was stopped 5 days before the procedure and was resumed within 24 hours after the procedure. Follow-up of patients continued for 30 days after the procedure. The primary outcomes were arterial thromboembolism (stroke, systemic embolism, or transient ischemic attack) and major bleeding., Results: In total, 1884 patients were enrolled, with 950 assigned to receive no bridging therapy and 934 assigned to receive bridging therapy. The incidence of arterial thromboembolism was 0.4% in the no-bridging group and 0.3% in the bridging group (risk difference, 0.1 percentage points; 95% confidence interval [CI], -0.6 to 0.8; P=0.01 for noninferiority). The incidence of major bleeding was 1.3% in the no-bridging group and 3.2% in the bridging group (relative risk, 0.41; 95% CI, 0.20 to 0.78; P=0.005 for superiority)., Conclusions: In patients with atrial fibrillation who had warfarin treatment interrupted for an elective operation or other elective invasive procedure, forgoing bridging anticoagulation was noninferior to perioperative bridging with low-molecular-weight heparin for the prevention of arterial thromboembolism and decreased the risk of major bleeding. (Funded by the National Heart, Lung, and Blood Institute of the National Institutes of Health; BRIDGE ClinicalTrials.gov number, NCT00786474.).

Background: The perioperative management of dabigatran in clinical practice is heterogeneous. We performed this study to evaluate the safety of perioperative management of dabigatran using a specified protocol., Methods and Results: Patients treated with dabigatran and planned for an invasive procedure were eligible for inclusion. The timing of the last dose of dabigatran before the procedure was based on the creatinine clearance and procedure-related bleeding risk. Resumption of dabigatran was prespecified according to the complexity of the surgery and consequences of a bleeding complication. Patients were followed up for 30 days for major bleeding (primary outcome), minor bleeding, arterial thromboembolism, and death. We included 541 cases: 324 procedures (60%) with standard risk of bleeding and 217 procedures (40%) with increased risk of bleeding. The last dose of dabigatran was at 24, 48, or 96 hours before surgery according to the protocol in 46%, 37%, and 6%, respectively, of the patients. Resumption was timed according to protocol in 77% with 75 mg as the first dose on the day of procedure in 40% of the patients. Ten patients (1.8%; 95% confidence interval, 0.7-3.0) had major bleeding, and 28 patients (5.2%; 95% confidence interval, 3.3-7.0) had minor bleeding events. The only thromboembolic complication was transient ischemic attack in 1 patient (0.2%; 95% confidence interval, 0-0.5), and there were 4 deaths unrelated to bleeding or thrombosis. Bridging was not used preoperatively but was administered in 9 patients (1.7%) postoperatively., Conclusion: Our protocol for perioperative management of dabigatran appears to be effective and feasible., (© 2015 American Heart Association, Inc.)

Importance: The risk of bleeding and recurrent venous thromboembolism (VTE) among patients receiving long-term warfarin sodium therapy for secondary VTE prevention who require temporary interruption of anticoagulant therapy for surgery or invasive diagnostic procedures has not been adequately described., Objective: To describe the rates of clinically relevant bleeding and recurrent VTE among patients in whom warfarin therapy is interrupted for invasive procedures and compare these rates among patients who did and did not receive bridge therapy., Design, Setting, and Participants: A retrospective cohort study was conducted at Kaiser Permanente Colorado, an integrated health care delivery system. Patients in whom warfarin therapy was interrupted for invasive diagnostic or surgical procedures between January 1, 2006, and March 31, 2012, were identified via queries of administrative data sets. A total of 1812 procedures in 1178 patients met inclusion criteria. Data on outcomes and exposures were collected between June 1, 2005, and April 30, 2012., Exposures: Use of bridge therapy vs no bridge therapy during warfarin interruption., Main Outcomes and Measures: Thirty-day clinically relevant bleeding, recurrent VTE, and all-cause mortality. Outcomes were verified via manual review of medical records., Results: Among the 1178 patients, the mean (SD) age was 66.1 (12.7) years, 830 procedures (45.8%) were in men, and the most common indication for warfarin therapy was deep vein thrombosis (56.3%). Most patients were considered to be at low risk for VTE recurrence at the time of warfarin interruption (1431 procedures [79.0%]) according to the consensus guidelines of the American College of Chest Physicians. Clinically relevant bleeding within 30 days after the procedure in the bridge therapy and non-bridge therapy groups occurred in 15 patients (2.7%) and 2 patients (0.2%), respectively (hazard ratio, 17.2; 95% CI, 3.9-75.1). There was no significant difference in the rate of recurrent VTE between the bridge and non-bridge therapy groups (0 vs 3; P = .56). No deaths occurred in either group., Conclusions and Relevance: Bridge therapy was associated with an increased risk of bleeding during warfarin therapy interruption for invasive procedures in patients receiving treatment for a history of VTE and is likely unnecessary for most of these patients. Further research is needed to identify patient- and procedure-related characteristics associated with a high risk of perioperative VTE recurrence during warfarin therapy interruption.

Background: In order to stratify patients with a first unprovoked venous thromboembolism (VTE) according to their recurrence risk and to identify those who would actually benefit from indefinite anticoagulation, three prediction models have been developed so far; none of them has been yet externally validated., Objective: To externally validate the Vienna Prediction Model (VPM), a prediction guide for estimating the recurrence risk after a first unprovoked VTE developed through Cox modeling and including sex, D-dimer and index VTE site as predictors., Patients/methods: Nine hundred and four patients pooled from five prospective studies evaluating the prognostic value of D-dimer for VTE recurrence served as the validation cohort. The validity of the VPM in stratifying patients according to their relative recurrence risk (discrimination) and in predicting the absolute recurrence risk (calibration) was tested with survival analysis methods., Results: The ability of the VPM to distinguish patients' risk for recurrent VTE in the validation cohort was at least as good as in the original cohort, with a calibration slope of 1.17 (95% confidence interval 0.71-1.64; P = 0.456 for the hypothesis of a significant difference from 1), and a c-statistic of 0.626 (vs. 0.651 in the original derivation cohort). The VPM absolute predictions in terms of cumulative rates tended to underestimate the observed recurrence rates at 12 months., Conclusions: By using a pooled individual patient database as a validation cohort, we confirmed the ability of the VPM to stratify patients with a first unprovoked VTE according to their risk of recurrence., (© 2015 International Society on Thrombosis and Haemostasis.)

In patients with atrial fibrillation (AF) who require interruption of dabigatran or warfarin for an elective surgery/procedure, the risks and benefits of perioperative bridging anticoagulation is uncertain.We accessed the database from RE-LY, a randomised trial comparing dabigatran with warfarin for stroke prevention in AF, to assess the potential benefits and risks of bridging. In patients who had a first interruption of dabigatran or warfarin for an elective surgery/procedure, we compared the risk for major bleeding (MB), stroke or systemic embolism (SSE) and any thromboembolism (TE) in patients who were bridged or not bridged during the period of seven days before until 30 days after surgery/procedure. We used multivariable Cox regression to adjust for potential confounders.Bridging was used more during warfarin interruption than dabigatran interruption (27.5 % vs 15.4 %; p< 0.001). With dabigatran interruption, bridged patients had more MB (6.5 % vs 1.8 %, p< 0.001) than those not bridged but bridged and not bridged groups did not differ for any TE (1.2 % vs 0.6 %, p=0.16) and SSE (0.5 % vs 0.3 %, p=0.46). With warfarin interruption, bridged patients had more MB (6.8 % vs 1.6 %, p< 0.001) and any TE (1.8 % vs 0.3 %, p=0.007) than those not bridged but bridged and not bridged groups did not differ for SSE (0.5 % vs 0.2 %, p=0.321). In conclusion, in patients who interrupted dabigatran or warfarin for a surgery/ procedure in the RE-LY trial, use of bridging anticoagulation appeared to increase the risk for major bleeding irrespective of dabigatran or warfarin interruption.

Background: In clinical practice, physicians are given the choice of selecting one of two dabigatran doses based on patient characteristics, with the lower dose typically used in patients at a higher risk of bleeding., Objectives: The objectives of the study were to (i) estimate the inter- and intra-patient variability in dabigatran levels with 110 mg (DE110) and 150 mg (DE150) doses, (ii) examine the effect of physicians' dose selection on levels in DE110 and DE150 subgroups, and (iii) explore whether a single trough measurement identifies patients with extreme levels on subsequent visits., Methods: In this prospective observational study of 100 patients with atrial fibrillation (AF), peak and trough levels of dabigatran were measured with the Hemoclot(®) assay at baseline and every 2 months thereafter (maximum four visits)., Results: Inter-patient variability in dabigatran levels (geometric coefficient of variation [gCV], 51-64%) was greater than intra-patient variability (gCV, 32-40%). Similar medians and distributions of levels were observed in DE110 and DE150 subgroups. Patients receiving DE110 were older, had lower renal function and weighed less than those receiving DE150. Up to 40% of patients whose trough levels were in the upper extremes, and up to 80% of patients whose trough levels were in the lower extremes at baseline, showed subsequent levels that fell in the middle quartiles., Conclusions: Our data support the practice of selecting the dabigatran dose based upon clinical characteristics because it results in similar levels of drug exposure in patients given DE110 or DE150. They do not support the concept that a single Hemoclot(®) measurement reliably identifies patients with consistently high or low values., (© 2014 International Society on Thrombosis and Haemostasis.)

Purpose: To review the evidence surrounding appropriate prophylaxis for venous thromboembolism (VTE) in patients undergoing surgery., Principal Findings: Appropriate prophylactic strategies for surgical patients have been defined in major society guidelines. We review the evidence behind these guidelines in a case-based format, including patients with a high risk of bleeding, history of heparin-induced thrombocytopenia, obesity, and cancer. Selecting the most suitable means for VTE prophylaxis includes evaluating patient, anesthetic, and surgical factors. Nevertheless, pharmacologic VTE prophylaxis will be appropriate for the vast majority of inpatients undergoing surgery., Conclusions: Venous thromboembolism is a serious but preventable complication of hospitalization, especially among surgical patients. Historically, it has accounted for a high burden of postoperative morbidity and mortality. In the Enhanced Recovery After Surgery era, our aim should be no less ambitious than the eradication of postoperative VTE.

Background: Normal D-dimer levels after withdrawal of anticoagulant therapy are associated with a reduced risk for recurrence in patients with unprovoked venous thromboembolism (VTE) and may justify stopping treatment., Objective: To determine whether patients with a first unprovoked VTE and negative D-dimer test result who stop anticoagulant therapy have a low risk for recurrence., Design: Prospective management study with blinded outcome assessment. (ClinicalTrials.gov: NCT00720915)., Setting: 13 university-affiliated clinical centers., Patients: 410 adults aged 75 years or younger with a first unprovoked proximal deep venous thrombosis or pulmonary embolism who had completed 3 to 7 months of anticoagulant therapy., Intervention: Anticoagulant therapy was stopped if D-dimer test results were negative and was not restarted if results were still negative after 1 month., Measurements: Recurrent VTE during an average follow-up of 2.2 years., Results: In 319 patients (78%) who had 2 negative D-dimer results and did not restart anticoagulant therapy, rates of recurrent VTE were 6.7% (95% CI, 4.8% to 9.0%) per patient-year overall (42 of 319), 9.7% (CI, 6.7% to 13.7%) per patient-year in men (33 of 180), 5.4% (CI, 2.5% to 10.2%) per patient-year in women with VTE not associated with estrogen therapy (9 of 81), and 0.0% (CI, 0.0% to 3.0%) per patient-year in women with VTE associated with estrogen therapy (0 of 58) (P = 0.001 for the 3-group comparison)., Limitations: Imprecision in female subgroups. Results may not be generalizable to different D-dimer assays from the one used in the study., Conclusion: The risk for recurrence in patients with a first unprovoked VTE who have negative D-dimer results is not low enough to justify stopping anticoagulant therapy in men but may be low enough to justify stopping therapy in women., Primary Funding Source: Canadian Institutes of Health Research.

Defining the safest perioperative anticoagulation management approach for patients who are receiving chronic anticoagulant therapy stroke prevention has been a challenging and longstanding dilemma, especially for patients with atrial fibrillation who constitute the most common patient group receiving long term anticoagulation. Using a case-based format, we summarize the findings of recent clinical trialswhich have helped to informed best practices for perioperative anticoagulant management in patients with atrial fibrillation and provide an algorithmic management approach to this problem. We have done so by exploring the evidence to address 3 key questions: Is it necessary to interrupt anticoagulation for a procedure? How to estimate a patient's risk for perioperative thromboembolism and bleeding? If chronic anticoagulation interruption is required, is bridging anticoagulation with heparin needed?

Background: Perioperative management with reduced-dose warfarin is of potential interest by eliminating the need for bridging while still maintaining a degree of anticoagulation. The outcomes of this regimen have not been well determined., Methods: In a randomized controlled trial we compared two regimens for management of anticoagulation with warfarin in patients with implantation of a pacemaker or defibrillator. Half dose of warfarin for 3-6 days, depending on the baseline international normalized ratio (INR), before surgery aiming at an INR of ≤ 1.7 was compared with interrupted warfarin for 5 days with preoperative bridging with low-molecular-weight heparin (LMWH) at therapeutic dose for 2.5 days. Main safety outcome was pocket hematoma. Secondary outcomes were major bleeding, thromboembolism - all within 1 month, days of hospitalization and number of patients requiring correction of INR with vitamin K., Results: The study was planned for 450 patients but it was discontinued prematurely due to a change in practice. Pocket hematoma occurred in 4 of 85 patients (5%) randomized to the bridged regimen and in 3 of 86 patients (3%) randomized to reduced-dose warfarin. One pocket hematoma in each group was severe. There were no major hemorrhages or thromboembolism within the 1-month window. Duration of hospitalization was similar in the two groups. Correction of INR the day before surgery with vitamin K had to be used for significantly more patients in the reduced-dose warfarin group (41%) than in the bridged regimen group (6%)., Conclusion: The reduced-dose warfarin regimen appeared to have similar safety after device implantation as interrupted warfarin with preoperative LMWH bridging. Due to premature discontinuation no firm conclusion can be drawn. The reduced-dose warfarin regimen often failed to achieve the intended preoperative INR. ClinicalTrials.gov Identifier: NCT 02094157., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

When counseling first-degree relatives of patients with venous thromboembolism (VTE), it is important to know whether factors other than thrombophilia influence their risk for thrombosis. We assessed the risk for VTE in 915 first-degree relatives of patients with provoked VTE, compared this with the risk in 1752 first-degree relatives of patients with unprovoked VTE, and then combined data from the 2 groups of relatives to identify predictors of thrombosis. There had been 123 VTEs in 2617 first-degree relatives (0.12 per 100 person-years). The risk for VTE in first-degree relatives was higher if the index cases had an unprovoked compared with a provoked VTE (odds ratio [OR], 2.38; 95% confidence interval [CI], 1.43-3.85), if the index case was younger (OR, 0.97 per year older; 95% CI, 0.96-0.99), and if an additional family member had VTE (OR, 2.71; 95% CI, 2.22-3.31). Among first-degree relatives of an index case with factor V Leiden or the prothrombin 20210A gene variant, the presence of these abnormalities also predicted thrombosis (OR, 4.42; 95% CI, 1.35-14.38). We conclude that thrombosis at a young age and unprovoked VTE predict VTE in first-degree relatives, and that the influence of these 2 factors is additive., (© 2014 by The American Society of Hematology.)

With advances in modern imaging techniques, portal vein thrombosis (PVT) is being increasingly diagnosed. It has a wide ranging clinical spectrum from being an asymptomatic state to a potentially life-threatening situation. It is not unusual to find it as an incidental finding in the abdominal imagings done for other reasons. It is commonly associated with cirrhosis and abdominal malignancies and also has a strong association with prothrombotic disorders. It is often difficult for the clinicians to decide whether PVT is acute or chronic. This poses great challenges to its management strategies that include anticoagulants, thrombolysis, and surgical options. Timely diagnosis and appropriate management have great bearings on its outcomes of morbidity and mortality. In this clinician-oriented review, we have provided a concise review of clinical aspects of PVT and discussed various management strategies while addressing the common questions that come to a physician's mind dealing with such a patient., (© The Author(s) 2013.)

Background: During long-term anticoagulation in atrial fibrillation, temporary interruptions (TIs) of therapy are common, but the relationship between patient outcomes and TIs has not been well studied. We sought to determine reasons for TI, the characteristics of patients undergoing TI, and the relationship between anticoagulant and outcomes among patients with TI., Methods and Results: In the Rivaroxaban Once Daily, Oral, Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF), a randomized, double-blind, double-dummy study of rivaroxaban and warfarin in nonvalvular atrial fibrillation, baseline characteristics, management, and outcomes, including stroke, non-central nervous system systemic embolism, death, myocardial infarction, and bleeding, were reported in participants who experienced TI (3-30 days) for any reason. The at-risk period for outcomes associated with TI was from TI start to 30 days after resumption of study drug. In 14 236 participants who received at least 1 dose of study drug, 4692 (33%) experienced TI. Participants with TI were similar to the overall ROCKET AF population in regard to baseline clinical characteristics. Only 6% (n=483) of TI incidences involved bridging therapy. Stroke/systemic embolism rates during the at-risk period were similar in rivaroxaban-treated and warfarin-treated participants (0.30% versus 0.41% per 30 days; hazard ratio [confidence interval]=0.74 [0.36-1.50]; P=0.40). Risk of major bleeding during the at-risk period was also similar in rivaroxaban-treated and warfarin-treated participants (0.99% versus 0.79% per 30 days; hazard ratio [confidence interval]=1.26 [0.80-2.00]; P=0.32)., Conclusions: TI of oral anticoagulation is common and is associated with substantial stroke risks and bleeding risks that were similar among patients treated with rivaroxaban or warfarin. Further investigation is needed to determine the optimal management strategy in patients with atrial fibrillation requiring TI of anticoagulation., Clinical Trial Registration Url: http://www.clinicaltrials.gov. Unique identifier: NCT00403767.

Residual venous obstruction (RVO) could improve the stratification of the risk of recurrence after unprovoked deep vein thrombosis (DVT), but results from clinical studies and study-level meta-analyses are conflicting. It was the objective of this analysis to determine if RVO is a valid predictor of recurrent venous thromboembolism (VTE) in patients with a first unprovoked DVT who had received at least three months of anticoagulant therapy. Individual patient data were obtained from the datasets of original studies, after a systematic search of electronic databases (Medline, Embase, Cochrane Library), supplemented by manual reviewing of the reference lists and contacting content experts. A multivariate, shared-frailty Cox model was used to calculate hazard ratios (HRs) for recurrent VTE, including, as covariates: RVO; age; sex; anticoagulation duration before RVO assessment; and anticoagulation continuation after RVO assessment. A total of 2,527 patients from 10 prospective studies were included. RVO was found in 1,380 patients (55.1%) after a median of six months from a first unprovoked DVT. Recurrent VTE occurred in 399 patients (15.8%) during a median follow-up of 23.3 months. After multivariate Cox analysis, RVO was independently associated with recurrent VTE (HR = 1.32, 95% confidence interval [CI]: 1.06-1.65). The association was stronger if RVO was detected early, i.e. at three months after DVT (HR = 2.17; 95% CI: 1.11-4.25), but non-significant if detected later, i.e. >6 months (HR = 1.19; 95% CI: 0.87-1.61). In conclusion, after a first unprovoked DVT, RVO is a weak overall predictor of recurrent VTE. The association is stronger if RVO is detected at an earlier time (3 months) after thrombosis.

Background: It is unclear how to appropriately manage discontinuation and resumption of antiplatelet therapy in patients with coronary stents who need noncardiac surgery. We undertook a systematic review of the literature to identify practice guideline statements regarding antiplatelet therapy in patients with coronary stents undergoing noncardiac surgery., Methods: We used six search strategies to identify practice guideline statements that comment on perioperative antiplatelet management for patients with coronary stents undergoing noncardiac surgery. Two independent reviewers assessed study eligibility, abstracted data, and completed quality assessment., Results: We identified 11 practice guidelines that met the eligibility criteria; these were included in the review. These guidelines advised that elective noncardiac surgery be delayed for at least 4 weeks after bare-metal stent implantation and at least 6 months after drug-eluting stent implantation. For elective surgery, all guidelines advised continuing acetylsalicylic acid (ASA) therapy whenever possible. If interruption of antiplatelet therapy was required, four guidelines advised to discontinue ASA/clopidogrel at least 5 days before surgery, while two guidelines advised to discontinue 7 to 10 days before surgery. Five guidelines provided varying guidance for the use of perioperative bridging during antiplatelet therapy interruption., Conclusions: Most current recommendations are based on expert opinion. This review highlights the need for well-designed prospective studies to identify optimal management strategies in patients with coronary stents who are on antiplatelet therapy and who need noncardiac surgery.

Managing patients in the perioperative setting receiving novel oral anticoagulation agents for thromboprophylaxis or stroke prevention with atrial fibrillation is an important consideration for clinicians. The novel oral anticoagulation agents include direct Factor Xa inhibitors rivaroxaban and apixaban, and the direct thrombin inhibitor dabigatran. In elective surgery, discontinuing their use is important, but renal function must also be considered because elimination is highly dependent on renal elimination. If bleeding occurs in patients who have received these agents, common principles of bleeding management as with any anticoagulant (including the known principles for warfarin) should be considered. This review summarizes the available data regarding the management of bleeding with novel oral anticoagulation agents. Hemodialysis is a therapeutic option for dabigatran-related bleeding, while in vitro studies showed that prothrombin complex concentrates are reported to be useful for rivaroxaban-related bleeding. Additional clinical studies are needed to determine the best method for reversal of the novel oral anticoagulation agents when bleeding occurs.

Objective: We compared the performance of aggregate data (AD)--based and individual patient data (IPD)-based meta-analyses to synthesize evidence on the ability of D-dimer to distinguish recurrence risk in patients with unprovoked venous thromboembolism (VTE) who stopped anticoagulation., Study Design and Setting: We compared the results of the published AD-based rate ratio of VTE recurrence for positive vs. negative D-dimer, estimated by a mixed-effect Poisson model, with those of the IPD-based hazard ratio obtained by a Cox regression stratified by trial. We performed three additional analyses to investigate the methodological reasons for differences between the two approaches, comparing the IPD Cox regression with AD generated from IPD Poisson regression (to control for differences in population on study), AD time-to-event meta-analysis, and AD generated from IPD meta-regression., Results: Published analyses agreed in direction and statistical significance when estimating the prognostic value of D-dimer even if IPD estimates suggested a stronger effect. The additional analyses suggested that differences in study populations might explain this slight difference. Poor reporting in published studies precluded a true comparison of AD- and IPD-based assessments of heterogeneity sources., Conclusion: AD and IPD meta-analyses yielded similar estimates of D-dimer effect to distinguish risk for recurrent VTE. The IPD approach was justified by the need to investigate sources of heterogeneity., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: Compression ultrasonography performed serially over a 7-day period is recommended for the diagnosis of deep vein thrombosis in symptomatic pregnant women, but whether this approach is safe is unknown. We evaluated the safety of withholding anticoagulation from pregnant women with suspected deep vein thrombosis following negative serial compression ultrasonography and iliac vein imaging., Methods: Consecutive pregnant women who presented with suspected deep vein thrombosis underwent compression ultrasonography and Doppler imaging of the iliac vein of the symptomatic leg(s). Women whose initial test results were negative underwent serial testing on 2 occasions over the next 7 days. Women not diagnosed with deep vein thrombosis were followed for a minimum of 3 months for the development of symptomatic deep vein thrombosis or pulmonary embolism., Results: In total, 221 pregnant women presented with suspected deep vein thrombosis. Deep vein thrombosis was diagnosed in 16 (7.2%) women by initial compression ultrasonography and Doppler studies; none were identified as having deep vein thrombosis on serial testing. One patient with normal serial testing had a pulmonary embolism diagnosed 7 weeks later. The overall prevalence of deep vein thrombosis was 7.7% (17/221); of these, 65% (11/17) of cases were isolated to the iliofemoral veins and 12% (2/17) were isolated iliac deep vein thromboses. The incidence of venous thromboembolism during follow-up was 0.49% (95% confidence interval [CI] 0.09%-2.71%). The sensitivity of serial compression ultrasonography with Doppler imaging was 94.1% (95% CI 69.2%-99.7%), the negative predictive value was 99.5% (95% CI 96.9%-100%), and the negative likelihood ratio was 0.068 (95% CI 0.01-0.39)., Interpretation: Serial compression ultrasonography with Doppler imaging of the iliac vein performed over a 7-day period excludes deep-vein thrombosis in symptomatic pregnant women.

Background: 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., Methods: 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., Results: 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., Conclusions: 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 novel oral anticoagulant drugs, comprising dabigatran, rivaroxaban, and apixaban, have emerged as compelling alternatives to vitamin K antagonists for stroke prevention in atrial fibrillation, and low‑molecular‑weight heparin for thromboprophylaxis following hip and knee arthroplasty. Rivaroxaban has also been approved for treatment of venous thromboembolism. However, the role of these drugs for the management of patients with an acute coronary syndrome (ACS) is less certain. The purpose of this review was to summarize the randomized trials evaluating novel oral anticoagulants in patients with an ACS and consider the reasons why these drugs have not been incorporated into routine clinical practice. In addition, the situation involving rivaroxaban, which has been approved for use in patients with an acute coronary syndrome in Europe but not in North America, is discussed.

Duplex ultrasound is the first-line diagnostic test for detecting lower limb deep-vein thrombosis (DVT) but it is time consuming, requires patient transport, and cannot be interpreted by most physicians. The accuracy of emergency physician-performed ultrasound (EPPU) for the diagnosis of DVT, when performed at the bedside, is unclear. We did a systematic review and meta-analysis of the literature, aiming to provide reliable data on the accuracy of EPPU in the diagnosis of DVT. The MEDLINE and EMBASE databases (up to August 2012) were systematically searched for studies evaluating the accuracy of EPPU compared to either colour-flow duplex ultrasound performed by a radiology department or vascular laboratory, or to angiography, in the diagnosis of DVT. Weighted mean sensitivity and specificity and associated 95% confidence intervals (CIs) were calculated using a bivariate random-effects regression approach. There were 16 studies included, with 2,379 patients. The pooled prevalence of DVT was 23.1% (498 in 2,379 patients), ranging from 7.4% to 47.3%. Using the bivariate approach, the weighted mean sensitivity of EPPU compared to the reference imaging test was 96.1% (95%CI 90.6-98.5%), and with a weighted mean specificity of 96.8% (95%CI:94.6-98.1%). Our findings suggest that EPPU may be useful in the management of patients with suspected DVT. Future prospective studies are warranted to confirm these findings.

Anticoagulant drugs are highly effective for the prevention and treatment of venous and arterial thromboembolism. However, their use is also associated with an increased risk for bleeding, with an associated ∼10% case-fatality rate. Appropriate strategies for the management and reversal of anticoagulant-associated bleeding are clinically important and, ideally, should be standardized. These include general resuscitation, and diagnosis and local treatment of the bleeding source, and one or more of the following interventions: transfusion of red cells; transfusion of clotting factor replacements; and administration of anticoagulant antidotes and other prohaemostatic agents. Reversal strategies for the 'conventional' anticoagulants are based largely on clinical evidence, whereas evidence to guide the management of bleeding associated with 'new' anticoagulants is emerging. This review provides an evidence-based, but practical, patient-focused approach for the management of bleeding associated with the old and new anticoagulants.

The periprocedural management of patients receiving long-term oral anticoagulant therapy remains a common but difficult clinical problem, with a lack of high-quality evidence to inform best practices. It is a patient's thromboembolic risk that drives the need for an aggressive periprocedural strategy, including the use of heparin bridging therapy, to minimize time off anticoagulant therapy, while the procedural bleed risk determines how and when postprocedural anticoagulant therapy should be resumed. Warfarin should be continued in patients undergoing selected minor procedures, whereas in major procedures that necessitate warfarin interruption, heparin bridging therapy should be considered in patients at high thromboembolic risk and in a minority of patients at moderate risk. Periprocedural data with the novel oral anticoagulants, such as dabigatran, rivaroxaban, and apixaban, are emerging, but their relatively short half-life, rapid onset of action, and predictable pharmacokinetics should simplify periprocedural use. This review aims to provide a practical, clinician-focused approach to periprocedural anticoagulant management.

Patients receiving anticoagulant or antiplatelet therapy who require noncardiac surgery represent a common yet challenging clinical problem. Clinicians must balance the risk of thromboembolic and major adverse cardiovascular events that are associated with interrupting these therapies, against the risk of bleeding from continuing these drugs in the perioperative period. Identifying patients at highest risk for such complications requires particular attention to the role of bridging therapy and the optimal timing and duration of drug withdrawal and resumption with surgery. Patients with coronary stents represent a population that requires specific considerations, due to the added risk and significant mortality associated with perioperative stent thrombosis. Minimizing this risk is dependent on several patient- and stent-specific factors. This review provides clinicians with a summary of the available evidence to facilitate a practical approach to the management of these patients while highlighting the need for continued research in this field., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Background: The assessment of patients with suspected deep vein thrombosis (DVT) remains challenging despite current diagnostic algorithms. (99m)Tc-labelled DI-DD3B6/22-80B3 Fab´ fragments ((99m)Tc-DI-80B3, ThromboView®) is a novel diagnostic test that uses a radiolabelled humanized monoclonal antibody fragment specific for the D-dimer region of cross-linked fibrin to detect DVT. This test has an anatomic component to locate DVT and a functional component to differentiate acute (newly formed) thrombus from inactive (old) thrombus., Methods: In a multi-centre prospective cohort trial we investigated the diagnostic accuracy and safety of (99m)Tc-DI-80B3 in consecutive patients with suspected DVT who had the diagnosis confirmed or excluded by venography., Results: We enrolled 94 patients with suspected DVT of whom 12 did not have (99m)Tc-DI-80B3 imaging, leaving 82 patients for the safety analysis. Of these patients, there were 16 with non-evaluable imaging (11 venography, 7 (99m)Tc-DI-80B3, both in two patients) leaving 66 patients for the accuracy analysis. (99m)Tc-DI-80B3 imaging was well-tolerated: 2 patients developed urticaria; none developed serious adverse events. For proximal DVT, the sensitivity (84.2%; 95% confidence interval [CI]: 62.4-94.5) and specificity (97.6%; CI: 83.3-99.4) were highest when the combined 0.25-hour and 3-hour (99m)Tc-DI-80B3 images were used. The accuracy was lower for distal DVT, irrespective of the images used. There were insufficient patients to comment on the accuracy of (99m)Tc-DI-80B3 imaging for suspected recurrent DVT., Conclusions: (99m)Tc-DI-80B3 (ThromboView®) is a novel diagnostic modality for patients with suspected DVT with a promising accuracy and safety profile that justifies additional clinical development in diagnostic accuracy and clinical management studies., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

The new oral anticoagulants dabigatran, rivaroxaban and apixaban have advantages over warfarin which include no need for laboratory monitoring, less drug-drug interactions and less food-drug interactions. However, there is no established antidote for patients who are bleeding or require emergent surgery and there is a paucity of evidence to guide the clinical care during these situations. Members of thrombosis and anticoagulation groups participating in the Thrombosis and Hemostasis Summit of North America formulated expert opinion guidance for reversing the anticoagulant effect of the new oral anticoagulants and suggest: routine supportive care, activated charcoal if drug ingestion was within a couple of hours, and hemodialysis if feasible for dabigatran. Also, the pros and cons of the possible use of four factor prothrombin complex concentrate are discussed., (Copyright © 2012 Wiley Periodicals, Inc.)

Context: Symptomatic venous thromboembolism (VTE) after total or partial knee arthroplasty (TPKA) and after total or partial hip arthroplasty (TPHA) are proposed patient safety indicators, but its incidence prior to discharge is not defined., Objective: To establish a literature-based estimate of symptomatic VTE event rates prior to hospital discharge in patients undergoing TPHA or TPKA., Data Sources: Search of MEDLINE, EMBASE, and the Cochrane Library (1996 to 2011), supplemented by relevant articles., Study Selection: Reports of incidence of symptomatic postoperative pulmonary embolism or deep vein thrombosis (DVT) before hospital discharge in patients who received VTE prophylaxis with either a low-molecular-weight heparin or a subcutaneous factor Xa inhibitor or oral direct inhibitor of factors Xa or IIa., Data Extraction and Synthesis: Meta-analysis of randomized clinical trials and observational studies that reported rates of postoperative symptomatic VTE in patients who received recommended VTE prophylaxis after undergoing TPHA or TPKA. Data were independently extracted by 2 analysts, and pooled incidence rates of VTE, DVT, and pulmonary embolism were estimated using random-effects models., Results: The analysis included 44,844 cases provided by 47 studies. The pooled rates of symptomatic postoperative VTE before hospital discharge were 1.09% (95% CI, 0.85%-1.33%) for patients undergoing TPKA and 0.53% (95% CI, 0.35%-0.70%) for those undergoing TPHA. The pooled rates of symptomatic DVT were 0.63% (95% CI, 0.47%-0.78%) for knee arthroplasty and 0.26% (95% CI, 0.14%-0.37%) for hip arthroplasty. The pooled rates for pulmonary embolism were 0.27% (95% CI, 0.16%-0.38%) for knee arthroplasty and 0.14% (95% CI, 0.07%-0.21%) for hip arthroplasty. There was significant heterogeneity for the pooled incidence rates of symptomatic postoperative VTE in TPKA studies but less heterogeneity for DVT and pulmonary embolism in TPKA studies and for VTE, DVT, and pulmonary embolism in TPHA studies., Conclusion: Using current VTE prophylaxis, approximately 1 in 100 patients undergoing TPKA and approximately 1 in 200 patients undergoing TPHA develops symptomatic VTE prior to hospital discharge.

An increasing number of patients are receiving long‑term oral anticoagulant therapy and the availability of new oral anticoagulants (OACs), which are easier to use than warfarin, will further expand the population of anticoagulated patients. As a consequence, an increasing number of patients will need perioperative anticoagulant management because of elective or nonelective surgery or procedures. The perioperative management of such patients is pertinent to a broad spectrum of physicians, including anesthesiologists, internists, and surgeons. The objectives of this review are to provide a clinically‑focused background on the pharmacology of warfarin and the new OACs and to suggest perioperative anticoagulant management strategies. This review will focus on the perioperative management of warfarin and new OACs who require urgent or emergent surgery or who require rapid anticoagulant reversal because of ongoing bleeding or high bleeding risk.

Objective: Deep vein thrombosis (DVT) prophylaxis remains underused in hospitalized medical patients despite strong recommendations that at-risk patients should receive prophylaxis. To understand this gap between knowledge and practice, we surveyed clinicians' perceptions about the importance of DVT prophylaxis, barriers to guideline implementation, and interventions to optimize prophylaxis., Methods: Paper- and electronic mail-based surveys were sent to 1553 internists, nurses, pharmacists, and physiotherapists in Ontario, Canada. Responses were scored on 7-point Likert scales. An important barrier to optimal DVT prophylaxis was 1 with a mean score ≥5, and interventions with high potential success or feasibility were those with mean scores ≥5., Results: DVT prophylaxis was perceived as important by all clinician groups but this did not appear to translate into knowledge about underutilization of current DVT prophylaxis strategies. Physicians and pharmacists recognized the underuse of DVT prophylaxis in medical patients, while nurses and physiotherapists tended to perceive prophylaxis strategies as appropriate. Lack of clear indications and contraindications for prophylaxis and concerns about bleeding risks were perceived as important barriers. Preprinted orders were considered the most potentially successful and feasible way to optimize prophylaxis., Conclusions: A considerable barrier to optimal DVT prophylaxis utilization may be that those healthcare providers best able to conduct a daily assessment of patients' need for prophylaxis underrecognize the problem that prophylaxis is underutilized in this population. Interventions to bridge the gap between knowledge and practice should consider preprinted orders outlining DVT risk factors, and educating front-line care providers prior to implementation of a top-down approach., (Copyright © 2011 Society of Hospital Medicine.)

Background: Few studies have assessed the effect of prothrombotic blood abnormalities on the risk of deep vein thrombosis (DVT) with hormone replacement therapy (HRT)., Methods: We studied postmenopausal women with suspected DVT in whom HRT use and prothrombotic blood abnormalities were sought. Cases had unprovoked DVT and controls had no DVT and without DVT risk factors. The risk of DVT was determined in women with and without prothrombotic abnormalities., Results: A total of 510 postmenopausal women with suspected DVT were assessed; 57 cases and 283 controls were identified. Compared to HRT, nonusers without the factor V Leiden mutation, the risk of DVT was increased in estrogen-progestin HRT users (odds ratio [OR], 3.2; 95% confidence interval [CI]: 1.2-8.6) and in nonusers with the factor V Leiden mutation (OR, 5.3; 1.9-15.4) and appears multiplied in users of estrogen-progestin HRT with the factor V Leiden mutation (OR, 17.1; 3.7-78). Compared to HRT, nonusers with normal factor VIII, the risk of DVT was increased in estrogen-progestin HRT users with normal factor VIII (OR, 2.8; 1.0-7.9) and in HRT nonusers with the highest factor VIII quartile (OR, 6.0; 2.1-17), and appears to be multiplied in women who are users of estrogen-progestin HRT with the highest factor VIII quartile (OR, 17.0; 3.6-80)., Conclusions: In postmenopausal women who are estrogen-progestin HRT users, the presence of the factor V Leiden mutation or an elevated factor VIII level appears to have a multiplicative effect on their overall risk of DVT, increasing it 17-fold compared to women without these blood abnormalities who are HRT nonusers.

The management of patients who are receiving warfarin, aspirin, clopidogrel, or combinations of these drugs and require their interruption because of an elective surgical or other invasive procedure is a common and sometimes challenging clinical problem. For the practicing clinician, there are 2 key issues for perioperative anticoagulant management: 1) having an approach to stratify patients according to their risk for thromboembolism when warfarin or antiplatelet drug therapy is interrupted, and also having an approach to stratify patients according to the risk of bleeding associated with the surgery or procedure; and 2) determining which patients may require bridging anticoagulation and, if required, how to administer bridging, typically with a low-molecular-weight heparin, before and after surgery in a manner that minimizes the risk for bleeding. The overall goal is to minimize patients' risk for thromboembolism and bleeding throughout the perioperative period. The objective of this article is to provide an evidence-based but practical approach relating to these 2 key issues in a manner than can be applied to everyday clinical practice.

Combination warfarin-ASA therapy is currently used in approximately 800,000 patients in North America as long-term treatment for the primary and secondary prevention of atherothrombotic and thromboembolic diseases. Despite a potentially complementary action of anticoagulant and antiplatelet drugs, the use of combination warfarin-ASA therapy is not based on compelling evidence of a net therapeutic benefit, with the exception of patients with a mechanical heart valve. On the other hand, there is more compelling and consistent evidence that combination warfarin-ASA therapy confers a 1.5- to 2.0-fold increased risk for serious bleeding compared with use of warfarin alone. In everyday practice, clinicians should combine the best available evidence with clinical judgment, considering that in most clinical scenarios, clinical practice guideline may not provide clear recommendations for patients who should, and should not, receive combination warfarin-ASA therapy. The objectives of this review are to describe which patients are receiving combined warfarin-aspirin therapy, to summarize the evidence for the therapeutic benefit and harm of combined warfarin-ASA therapy, and to suggest practical guidelines as to which patients should, and should not, receive such treatment., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Although the risk for bleeding during long-term warfarin therapy is established, little is known about the clinical impact following warfarin-associated bleeding and the management of anticoagulant resumption after a bleed. We performed a retrospective chart review of patients who suffered a warfarin-associated bleed that required hospitalization or that occurred during hospitalization. We determined the proportion of patients who required a blood product transfusion, a surgical or other invasive procedure or admission to an intensive care unit, and the duration of hospitalization. We also determined the case-fatality rate of bleeding and described post-bleed resumption of anticoagulation. We studied 142 patients (70 women) hospitalized with warfarin-associated bleeding with a mean age of 73 years. The most prevalent sites of bleeding were the gastrointestinal tract (40.8%) and urinary tract (14.1%). Of all bleeding episodes, 72 (50.1%) were classified as major bleeds. There were 66 (46.4%) patients who required either endoscopy, surgery or admission to an intensive care unit, and the mean duration of hospitalization was 23 days. The case fatality rate of major bleeding was 9.5%. Among patients in whom warfarin was restarted, 8.3% suffered recurrent bleeding. Warfarin-associated bleeding appears to confer considerable morbidity related to transfusion and hospitalization, approximately 1 in 10 major bleeds are fatal, and 1 in 12 patients will re-bleeding after warfarin resumption.

Antiplatelet agents are a cornerstone of therapy for patients with atherosclerotic vascular disease. There is presently a lack of comprehensive guidelines focusing on the use of antiplatelet drugs in patients currently manifesting or at elevated risk of cardiovascular disease. The Canadian Antiplatelet Therapy Guidelines Committee reviewed existing disease-based guidelines and subsequently published literature and used expert opinion and review to develop guidelines on the use of antiplatelet therapy in the outpatient setting. This full document has been summarized in an Executive Summary published in the Canadian Journal of Cardiology and may be found at http://www.ccs.ca/. Antiplatelet therapy appears to be generally underused, perhaps in part because of a lack of clear, evidence-based guidance. Here, we provide specific guidelines for secondary prevention in patients discharged from hospital following acute coronary syndromes, post-percutaneous coronary intervention, post-coronary artery bypass grafting, patients with a history of transient cerebral ischemic events or strokes, and patients with peripheral arterial disease. Issues related to primary prevention are also addressed, in addition to special clinical contexts such as diabetes, heart failure, chronic kidney disease, pregnancy/lactation, and perioperative management. Recommendations are provided regarding pharmacologic interactions that may occur during combination therapy with warfarin, clopidogrel and proton-pump inhibitors, or acetylsalicylic acid and nonsteroidal anti-inflammatory drugs, as well as for the management of bleeding complications., (Copyright © 2011. Published by Elsevier Inc.)

In the past decade, antithrombotic therapy research has focused on the development of new oral anticoagulant drugs to replace vitamin K antagonists for stroke prevention in patients with chronic atrial fibrillation, for preventing cardiovascular complications of acute coronary syndromes, and for the prevention and treatment of venous thromboembolism. The most anticipated studies relate to the use of new oral anticoagulants to replace vitamin K antagonists for the prevention of stroke in patients with atrial fibrillation. This review will focus on dabigatran, the first non-vitamin K anticoagulant approved for this clinical indication, and will assess the RE-LY trial (Randomized Evaluation of Long Term Anticoagulant Therapy) findings according to the level of anticoagulation control in warfarin-treated patients. The objectives of this review are: 1) to provide an overview of dabigatran, highlighting clinically relevant properties; 2) to provide a commentary on the study by Wallentin et al. within the context of how the quality of anticoagulation control affects warfarin efficacy and safety; and 3) to consider which patients with chronic atrial fibrillation should receive and which may not need to receive dabigatran.

Venous thromboembolism (VTE), which encompasses deep vein thrombosis and pulmonary embolism, is a leading cause of preventable morbidity and mortality following hospitalization. In the last decade, investigators have used randomized controlled trials to assess the efficacy and safety of various methods of VTE prevention for more than 20,000 medical patients. Identifying medical patients at risk for VTE and providing effective prophylaxis is now an important health care priority to reduce the burden of this morbid and sometimes fatal disease. Pharmacologic prophylaxis is the mainstay of VTE prevention. It is effective, safe, and cost effective. Multiple scientific guidelines support VTE prophylaxis in medical patients. Regulatory and accreditation agencies have mandated that hospitals use formalized systems to assess VTE risk and provide clinically appropriate prophylaxis measures to patients at risk., (Copyright © 2010 Elsevier Inc. All rights reserved.)