Christopher Hillis

Mortality outcomes in patients receiving direct oral anticoagulants: a systematic review and meta-analysis of randomized controlled trials.

Direct oral anticoagulants (DOACs) are widely used as an alternative for warfarin. However, the impact of DOACs on mortality outcomes compared with warfarin remains unclear.

Hemodialysis for the treatment of dabigatran-associated bleeding: a case report and systematic review

Dabigatran, a direct thrombin inhibitor, is effective for the treatment of venous thromboembolism and the prevention of stroke and systemic embolism resulting from atrial fibrillation. The most effective way of reversing the anticoagulant effect of dabigatran in patients who have bleeding complications is unknown.

Thromboembolic events, recurrent bleeding and mortality after resuming anticoagulant following gastrointestinal bleeding

Gastrointestinal (GI) bleeding commonly complicates anticoagulant therapy. We aimed to systematically review the published literature to determine the risk of thromboembolism, recurrent GI bleeding and mortality for patients on long-term anticoagulation who experience GI bleeding based on whether anticoagulation therapy was resumed. We performed a systematic review of phase III randomised controlled trials and cohort studies in patients with atrial fibrillation or venous thromboembolism who received oral anticoagulant. We searched MEDLINE, EMBASE and CENTRAL (from 1996-July 2014), conferences abstracts (from January 2006-July 2014) and www.clinicaltrials.gov (up to the last week of July 2014) with no language restriction. Two reviewers independently performed study selection, data extraction and study quality assessment. A total of three studies were included in the meta-analysis. The resumption of warfarin was associated with a significant reduction in thromboembolic events (hazard ratio [HR] 0.68, 95% confidence interval [CI] 0.52 to 0.88, p<0.004, I(²)=82%). There was an increase in recurrent GI bleeding but not statistically significant for patients who restarted warfarin compared to those who did not (HR 1.20, 95% CI 0.97 to 1.48, p = 0.10, I(²) = 0%). Resumption of warfarin was associated with significant reduction in mortality (HR 0.76, 95% CI 0.66 to 0.88, p<0.001, I(²) = 87%). This meta-analysis demonstrates that resumption of warfarin following interruption due to GI bleeding is associated with a reduction in thromboembolic events and mortality without a statistically significant increase in recurrent GI bleeding.

Prothrombin complex concentrates versus fresh frozen plasma for warfarin reversal. A systematic review and meta-analysis.

Urgent reversal of warfarin is required for patients who experience major bleeding or require urgent surgery. Treatment options include the combination of vitamin K and coagulation factor replacement with either prothrombin complex concentrate (PCC) or fresh frozen plasma (FFP). However, the optimal reversal strategy is unclear based on clinically relevant outcomes. We searched in MEDLINE, EMBASE and Cochrane library to December 2015. Thirteen studies (5 randomised studies and 8 observational studies) were included. PCC use was associated with a significant reduction in all-cause mortality compared to FFP (OR= 0.56, 95 % CI; 0.37-0.84, p=0.006). A higher proportion of patients receiving PCC achieved haemostasis compared to those receiving FFP, but this was not statistically significant (OR 2.00, 95 % CI; 0.85-4.68). PCC use was more likely to achieve normalisation of international normalised ratio (INR) (OR 10.80, 95 % CI; 6.12-19.07) and resulted in a shorter time to INR correction (mean difference -6.50 hours, 95 %CI; -9.75 to -3.24). Red blood cell transfusion was not statistically different between the two groups (OR 0.88, 95 % CI: 0.53-1.43). Patients receiving PCC had a lower risk of post-transfusion volume overload compared to FFP (OR 0.27, 95 % CI; 0.13-0.58). There was no statistically significant difference in the risk of thromboembolism following administration of PCC or FFP (OR 0.91, 95 % CI; 0.44-1.89). In conclusion, as compared to FFP, the use of PCC for warfarin reversal was associated with a significant reduction in all-cause mortality, more rapid INR reduction, and less volume overload without an increased risk of thromboembolic events.

Major arterial events in patients with chronic myeloid leukemia treated with tyrosine kinase inhibitors: a meta-analysis

Abstract There is growing evidence that tyrosine kinase inhibitors (TKIs) may be associated with an increased risk of arterial events. We performed a meta-analysis to estimate the incidence of arterial events in patients with CML treated with TKIs. We identified 29 studies enrolling 15,706 patients. The incidence rates of composite of major arterial events were 0.8 per 100 patient-years for non-TKI treatments, 1.1 per 100 patient-years for dasatinib, 0.1 per 100 patient-years for imatinib, 0.4 per 100 patient-years for bosutinib, 2.8 per 100 patient-years for nilotinib and 10.6 per 100 patient-years for ponatinib. The relative risk (RR) for nilotinib compared with imatinib suggests a significantly increased risk of the composite of major arterial events with nilotinib treatment (RR 5.3; 95%CI 3.0–9.3, p < 0.001). This study demonstrates that, patients who received nilotinib or ponatinib had a greater number of major arterial events when compared to non-TKI-, imatinib-, dasatinib- and bosutinib-treated patients.

Acute phase treatment of VTE: Anticoagulation, including non-vitamin K antagonist oral anticoagulants

The acute phase of venous thromboembolism (VTE) treatment focuses on the prompt and safe initiation of full-dose anticoagulation to decrease morbidity and mortality. Immediate management consists of resuscitation, supportive care, and thrombolysis for patients with haemodynamically significant pulmonary embolism (PE) or limb-threatening deep-vein thrombosis (DVT). Patients with contraindications to anticoagulants are considered for vena cava filters. Disposition for the acute treatment of VTE is then considered based on published risk scores and the patients social status, as the first seven days carries the highest risk for VTE recurrence, extension and bleeding due to anticoagulation. Next, a review of: immediate and long-term bleeding risk, comorbidities (i. e. active cancer, renal failure, obesity, thrombophilia), medications, patient preference, VTE location and potential for pregnancy should be undertaken. This will help determine the most suitable anticoagulant for immediate treatment. The non-vitamin K antagonist oral anticoagulants (NOACs), including the factor Xa inhibitors apixaban, edoxaban and rivaroxaban as well as the direct-thrombin inhibitor dabigatran, are increasing the convenience of and options available for VTE treatment. Current options for immediate treatment include low-molecular-weight heparin (LMWH), unfractionated heparin (UFH), fondaparinux, apixaban, or rivaroxaban. LMWH or UFH may be continued as monotherapy or transitioned to treatment with a VKA, dabigatran or edoxaban. This review describes the upfront treatment of VTE and the evolving role of NOACs in the contemporary management of VTE.

Current understanding of bleeding with ibrutinib use: a systematic review and meta-analysis

Ibrutinib therapy was associated with an increased risk of bleeding in previous trials. In this systematic review and meta-analysis of published trials including patients treated with ibrutinib, the relative risk (95% confidence interval [CI]) of overall bleeding was significantly higher in ibrutinib recipients (2.72 [1.62-6.58]), but major bleeding did not show a significant difference (1.66 [0.96-2.85]). The incidences (95% CI) of major bleeding and any bleeding were 3.0 (2.3-3.7) and 20.8 (19.1-22.1) per 100 patient-years, respectively. This analysis is limited by reporting bias from variable ascertainment of bleeding and lack of allocation concealment in some studies and differing exposures between groups, leading to potential overestimation of event rates in the ibrutinib group.

A systematic review of definitions and reporting of bleeding outcome measures in haemophilia.

Bleeding frequency is an important outcome commonly used in haemophilia studies. There is a variation in practice in how bleeding is measured and defined.

The Canadian Choosing Wisely campaign: the Canadian Hematology Society’s top five tests and treatments

Choosing Wisely Canada (CWC), a medical stewardship campaign, encourages dialogue between physicians and patients to promote high-quality decision-making. Medical societies develop lists of tests, treatments, and procedures that are unnecessary, reduce value, and may cause harm. The Canadian Hematology Society (CHS) elicited suggestions for CWC recommendations from its members and received 35 unique suggestions. A working group rated these based on their potential for harm, benefit, frequency of use and value. Twelve highly ranked items were subjected to systematic evidence review. The final items were included in the list if they were of sufficient evidence base and met pre-defined core principles. The CHS-CWC recommendations are: to avoid IVIG treatment for asymptomatic immune thrombocytopenia, not bridge warfarin in low-risk patients going for procedures, not perform thrombophilia testing in the workup of early pregnancy loss, avoid fine-needle aspiration in lymphoma diagnosis, and not transfuse red blood cells for an arbitrary hemoglobin threshold. Through implementation of these recommendations, physicians will reduce potential harm to patients and increase the value of health care.

Audit of provincial IVIG Request Forms and efficacy documentation in four Ontario tertiary care centres

Retrospective audit of IVIG Request Forms in four Ontario tertiary care centres: to determine the case mix of new IVIG requests, to authenticate information provided, and to determine documentation of clinical efficacy.