Menaka Pai

Strategies to enhance venous thromboprophylaxis in hospitalized medical patients (SENTRY): a pilot cluster randomized trial

BackgroundVenous 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.MethodsWe 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.ResultsA 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.ConclusionsHospitals 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.

Fondaparinux treatment of acute heparin-induced thrombocytopenia confirmed by the serotonin-release assay: a 30-month, 16-patient case series

See also Greinacher A. Immunogenic but effective: the HIT‐fondaparinux brain puzzler. This issue, pp 2386–8; Goldfarb MJ, Blostein MD. Fondaparinux in acute heparin‐induced thrombocytopenia: a case series. This issue, pp 2501–3.

Statins in the prevention of venous thromboembolism: A meta-analysis of observational studies

INTRODUCTION Studies have established a relationship between inflammation and venous thromboembolism (VTE). Though statins modulate inflammation, it is uncertain if they prevent VTE in heterogeneous populations. A recent randomized trial demonstrated that statins prevent VTE in healthy older adults, yet this has not been well established in other groups, including younger individuals and individuals with comorbidities. The objective of this meta-analysis was to estimate the effect of statins on VTE in a heterogeneous group of adults. METHODS We systematically reviewed the effect of statins in preventing VTE in adult inpatients and outpatients. We systematically searched MEDLINE (1966-Jan 2010), EMBASE (1980-Jan 2010), Google Scholar, Cochrane Library, PapersFirst, ProceedingsFirst, and ISI Web of Science, manually reviewed references, and contacted experts. Observational studies that compared any dose of statin to no statin or placebo, examined inpatients or outpatients, and assessed VTE, pulmonary embolism, and/or deep vein thrombosis were included. Study selection, data abstraction and study quality evaluation (using the Newcastle-Ottawa Scale) were independently conducted in duplicate. RESULTS Four cohort studies and four case-control studies met criteria. Comparing statins to control, the odds ratio for VTE was 0.67 (95% confidence interval 0.53, 0.84), and for deep vein thrombosis was 0.53 (95% confidence interval 0.22, 1.29). The association was attenuated in lower-quality studies and studies enrolling older individuals. CONCLUSIONS Further well-designed trials are needed to evaluate the risks and benefits of statins in preventing VTE in heterogenous populations of adults, identify high-risk subgroups, and analyze cost-effectiveness of statin use for this indication.

Design of the rivaroxaban for heparin-induced thrombocytopenia study

Rivaroxaban is an ideal potential candidate for treatment of heparin-induced thrombocytopenia (HIT) because it is administered orally by fixed dosing, requires no laboratory monitoring and is effective in the treatment of venous and arterial thromboembolism in other settings. The Rivaroxaban for HIT study is a prospective, multicentre, single-arm, cohort study evaluating the incidence of new symptomatic venous and arterial thromboembolism in patients with suspected or confirmed HIT who are treated with rivaroxaban. Methodological challenges faced in the design of this study include heterogeneity of the patient population, differences in the baseline risk of thrombosis and bleeding dependent on whether HIT is confirmed or just suspected, and heterogeneity in laboratory confirmation of HIT. The rationale for how these challenges were addressed and the final design of the Rivaroxaban for HIT study is reviewed.

NHF‐McMaster Guideline on Care Models for Haemophilia Management

This guideline was developed to identify evidence‐based best practices in haemophilia care delivery, and discuss the range of care providers and services that are most important to optimize outcomes for persons with haemophilia (PWH) across the United States. The guideline was developed following specific methods described in detail in this supplement and based on the GRADE (Grading of Recommendations, Assessment, Development and Evaluation approach). Direct evidence from published literature and the haemophilia community, as well as indirect evidence from other chronic diseases, were reviewed, synthesized and applied to create evidence‐based recommendations. The Guideline panel suggests that the integrated care model be used over non‐integrated care models for PWH (conditional recommendation, moderate certainty in the evidence). For PWH with inhibitors and those at high risk for inhibitor development, the same recommendation was graded as strong, with moderate certainty in the evidence. The panel suggests that a haematologist, a specialized haemophilia nurse, a physical therapist, a social worker and round‐the‐clock access to a specialized coagulation laboratory be part of the integrated care team, over an integrated care team that does not include all of these components (conditional recommendation, very low certainty in the evidence). Based on available evidence, the integrated model of care in its current structure, is suggested for optimal care of PWH. There is a need for further appropriately designed studies that address unanswered questions about specific outcomes and the optimal structure of the integrated care delivery model in haemophilia.

Failure of anticoagulant thromboprophylaxis: risk factors in medical-surgical critically ill patients

Objectives:To identify risk factors for failure of anticoagulant thromboprophylaxis in critically ill patients in the ICU. Design:Multivariable regression analysis of thrombosis predictors from a randomized thromboprophylaxis trial. Setting:Sixty-seven medical-surgical ICUs in six countries. Patients:Three thousand seven hundred forty-six medical-surgical critically ill patients. Interventions:All patients received anticoagulant thromboprophylaxis with low-molecular-weight heparin or unfractionated heparin at standard doses. Measurements and Main Results:Independent predictors for venous thromboembolism, proximal leg deep vein thrombosis, and pulmonary embolism developing during critical illness were assessed. A total of 289 patients (7.7%) developed venous thromboembolism. Predictors of thromboprophylaxis failure as measured by development of venous thromboembolism included a personal or family history of venous thromboembolism (hazard ratio, 1.64; 95% CI, 1.03–2.59; p = 0.04) and body mass index (hazard ratio, 1.18 per 10-point increase; 95% CI, 1.04–1.35; p = 0.01). Increasing body mass index was also a predictor for developing proximal leg deep vein thrombosis (hazard ratio, 1.25; 95% CI, 1.06–1.46; p = 0.007), which occurred in 182 patients (4.9%). Pulmonary embolism occurred in 47 patients (1.3%) and was associated with body mass index (hazard ratio, 1.37; 95% CI, 1.02–1.83; p = 0.035) and vasopressor use (hazard ratio, 1.84; 95% CI, 1.01–3.35; p = 0.046). Low-molecular-weight heparin (in comparison to unfractionated heparin) thromboprophylaxis lowered pulmonary embolism risk (hazard ratio, 0.51; 95% CI, 0.27–0.95; p = 0.034) while statin use in the preceding week lowered the risk of proximal leg deep vein thrombosis (hazard ratio, 0.46; 95% CI, 0.27–0.77; p = 0.004). Conclusions:Failure of standard thromboprophylaxis using low-molecular-weight heparin or unfractionated heparin is more likely in ICU patients with elevated body mass index, those with a personal or family history of venous thromboembolism, and those receiving vasopressors. Alternate management or incremental risk reduction strategies may be needed in such patients.

Neutralization of Heparin Activity

Heparin is the mainstay in the treatment and prevention of thrombosis in such diverse clinical settings as venous thromboembolism, acute coronary syndrome, cardiopulmonary bypass, and hemodialysis. However, the major complication of heparin - like that of all anticoagulants - is bleeding. Heparin may need to be reversed in the following settings: clinically significant bleeding; prior to an invasive procedure; at the conclusion of a procedure involving extracorporeal circulation (e.g., cardiopulmonary bypass, dialysis). This chapter discusses protamine sulfate, as well as several other agents that are able to neutralize heparin, including their pharmacological properties, indications, dosing, and efficacy.

Direct oral anticoagulants for treatment of HIT: update of Hamilton experience and literature review

Direct oral anticoagulants (DOACs) are attractive options for treatment of heparin-induced thrombocytopenia (HIT). We report our continuing experience in Hamilton, ON, Canada, since January 1, 2015 (when we completed our prospective study of rivaroxaban for HIT), using rivaroxaban for serologically confirmed HIT (4Ts score ≥4 points; positive platelet factor 4 [PF4]/heparin immunoassay, positive serotonin-release assay). We also performed a literature review of HIT treatment using DOACs (rivaroxaban, apixaban, dabigatran, edoxaban). We focused on patients who received DOAC therapy for acute HIT as either primary therapy (group A) or secondary therapy (group B; initial treatment using a non-DOAC/non-heparin anticoagulant with transition to a DOAC during HIT-associated thrombocytopenia). Our primary end point was occurrence of objectively documented thrombosis during DOAC therapy for acute HIT. We found that recovery without new, progressive, or recurrent thrombosis occurred in all 10 Hamilton patients with acute HIT treated with rivaroxaban. Data from the literature review plus these new data identified a thrombosis rate of 1 of 46 patients (2.2%; 95% CI, 0.4%-11.3%) in patients treated with rivaroxaban during acute HIT (group A, n = 25; group B, n = 21); major hemorrhage was seen in 0 of 46 patients. Similar outcomes in smaller numbers of patients were observed with apixaban (n = 12) and dabigatran (n = 11). DOACs offer simplified management of selected patients, as illustrated by a case of persisting (autoimmune) HIT (>2-month platelet recovery with inversely parallel waning of serum-induced heparin-independent serotonin release) with successful outpatient rivaroxaban management of HIT-associated thrombosis. Evidence supporting efficacy and safety of DOACs for acute HIT is increasing, with the most experience reported for rivaroxaban.

Loading dose vs. maintenance dose of warfarin for reinitiation after invasive procedures: a randomized trial.

There is uncertainty regarding the optimal dosing regimen for the resumption of warfarin after interruption for invasive procedures.

Methodology for the development of the NHF-McMaster Guideline on Care Models for Haemophilia Management

Rigorous and transparent methods are necessary to develop clinically relevant and evidence‐based practice guidelines. We describe the development of the National Hemophilia Foundation‐McMaster Guideline on Care Models for Haemophilia Management, which addresses best practices in haemophilia care delivery.