Login to your account

Username *
Password *
Remember Me

Blog With Right Sidebar

    Vous êtes ici :  
  1. Accueil
  2. Blog With Right Sidebar

Treatment and Prevention of Heparin-Induced Thrombocytopenia: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines.

Heparin-induced thrombocytopenia (HIT) is an antibody-mediated adverse drug reaction that can lead to devastating thromboembolic complications, including pulmonary embolism, ischemic limb necrosis necessitating limb amputation, acute myocardial infarction, and stroke.
METHODS: The methods of this guideline follow the Methodology for the Development of Antithrombotic Therapy and Prevention of Thrombosis Guidelines: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines in this supplement.
RESULTS: Among the key recommendations for this article are the following: For patients receiving heparin in whom clinicians consider the risk of HIT to be > 1%, we suggest that platelet count monitoring be performed every 2 or 3 days from day 4 to day 14 (or until heparin is stopped, whichever occurs first) (Grade 2C). For patients receiving heparin in whom clinicians consider the risk of HIT to be < 1%, we suggest that platelet counts not be monitored (Grade 2C). In patients with HIT with thrombosis (HITT) or isolated HIT who have normal renal function, we suggest the use of argatroban or lepirudin or danaparoid over other nonheparin anticoagulants (Grade 2C). In patients with HITT and renal insufficiency, we suggest the use of argatroban over other nonheparin anticoagulants (Grade 2C). In patients with acute HIT or subacute HIT who require urgent cardiac surgery, we suggest the use of bivalirudin over other nonheparin anticoagulants or heparin plus antiplatelet agents (Grade 2C).
CONCLUSIONS: Further studies evaluating the role of fondaparinux and the new oral anticoagulants in the treatment of HIT are needed.

Primary prophylaxis for venous thromboembolism in ambulatory cancer patients receiving chemotherapy.

Venous thromboembolism (VTE) often complicates the clinical course of cancer disease. The risk is further increased by chemotherapy but the safety and efficacy of primary thromboprophylaxis in cancer patients treated with chemotherapy is uncertain.
OBJECTIVES: To assess the efficacy and safety of primary thromboprophylaxis in ambulatory cancer patients receiving chemotherapy.
SEARCH METHODS: The Cochrane Peripheral Vascular Diseases Group searched their Specialised Register (last searched 3 May 2011) and CENTRAL (2011, Issue 2). The authors searched clinical trials registries and reference lists of relevant studies.
SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing unfractionated heparin (UFH), low molecular weight heparin (LMWH), vitamin K antagonists (VKA), direct thrombin inhibitors, direct factor Xa inhibitors or mechanical intervention to no intervention or placebo; or comparing two different anticoagulants.
DATA COLLECTION AND ANALYSIS: Data were extracted on methodological quality, patients, interventions and outcomes including symptomatic VTE and major bleeding as the primary effectiveness and safety outcomes, respectively.
MAIN RESULTS: Nine RCTs with a total of 3538 patients were considered. None of the RCTs tested UFH, fondaparinux, direct factor Xa inhibitors or mechanical interventions. Overall, the risk of bias was low in most of the studies. LMWH, when compared with inactive control, significantly reduced the incidence of symptomatic VTE (risk ratio (RR) 0.62, 95% confidence interval (CI) 0.41 to 0.93) with no evidence of heterogeneity (I(2) = 0%). The number needed to treat to prevent a symptomatic VTE was 60. LMWH was associated with a 60% increase in major bleeding when compared with inactive control, although this was not statistically significant (RR 1.57, 95% CI 0.69 to 3.60; I(2) = 10%). There was a 45% reduction in overall VTE (RR 0.55, 95% CI 0.34 to 0.88; I(2) = 0%) while for symptomatic pulmonary embolism, asymptomatic VTE, minor bleeding and one-year mortality the differences between the LMWH and control groups were not statistically significant. The effect of the vitamin K antagonist warfarin on preventing symptomatic VTE, measured in only one study, was not statistically significant (RR 0.15, 95% CI 0.02 to 1.20). In one RCT of patients with myeloma, LMWH was associated with a 67% reduction in symptomatic VTE (RR 0.33, 95% CI 0.14 to 0.83) compared with warfarin, with no differences in major bleeding. Antithrombin, evaluated in one study on paediatric patients, had no significant effect on VTE nor major bleeding when compared with inactive control.
AUTHORS' CONCLUSIONS: Primary thromboprophylaxis with LMWH significantly reduced the incidence of symptomatic VTE in ambulatory cancer patients treated with chemotherapy. However, the lack of power hampers definite conclusions on the effects on major safety outcomes, which mandates additional studies to determine the risk to benefit ratio of LMWH in this setting.

Computed tomographic pulmonary angiography and pulmonary embolism: predictive value of a d-dimer assay.

Computed tomographic pulmonary angiography (CTPA) is increasingly being used as first investigation for suspected pulmonary embolism (PE). The investigation has high predictive value, but is resource and time intensive and exposes patients to considerable radiation. Our aim was to assess the potential value of a negative d-dimer assay to exclude pulmonary emboli and reduce the number of performed CTPAs.
METHODS: All CTPAs performed in a Scottish secondary care hospital for a fourteen month period were retrospectively reviewed. Collected data included the presence or absence of PE, d-dimer results and patient demographics. PE positive CTPAs were reviewed by a specialist panel.
RESULTS: Pulmonary embolisms were reported for 66/405 (16.3%) CTPAs and d-dimer tests were performed for 216 (53%). 186/216 (86%) patients had a positive and 30 (14%) a negative d-dimer result. The panel agreed 5/66 (7.6%) false positive examinations. The d-dimer assay's negative predictive value was 93.3% (95% CI = 76.5%-98.8%) based on the original number of positive CTPAs and 100% (95% CI = 85.9%-100%) based on expert review. Significant non-PE intrapulmonary pathology was reported for 312/405 (77.0) CTPAs, including 13 new diagnoses of carcinoma.
CONCLUSIONS: We found that a low d-dimer score excluded all pulmonary embolisms, after a further specialist panel review identified initial false positive reports. However, current evidence-based guidelines still recommend that clinicians combine a d-dimer result with a validated clinical risk score when selecting suitable patients for CTPA. This may result in better use of limited resources, prevent patients being exposed to unnecessary irradiation and prevent potential complications as a result of iodinated contrast.

Bevacizumab-induced serious side-effects: a review of the French pharmacovigilance database.

PURPOSE: Bevacizumab, a recombinant humanized monoclonal antibody to vascular endothelial growth factor, is widely used in association with standard chemotherapy in metastatic cancer. Well tolerated, bevacizumab is sometimes associated with serious adverse drug reactions (ADRs). The objective of this study is to describe the profile of ADRs related to bevacizumab and reported to the French Pharmacovigilance system.
METHOD: All serious cases of ADRs associated with bevacizumab recorded in the French Pharmacovigilance database up to November 31, 2010 were identified and analyzed, focusing on patient information, drug exposure, and characteristics of the ADRs. Categorical variables were compared using the chi-square test when appropriate.
RESULTS: A total of 351 serious cases involving 626 ADRs were recorded in the database during the study interval. The most frequent ADRs reported involved the gastrointestinal system (21.9%). The most frequent ADRs included gastrointestinal perforation (4.8%), thromboembolic events (4.0%), pulmonary embolism (3.2%), hypertension (2.7%), gastrointestinal hemorrhage (2.7%), and cerebral hemorrhage or vascular accident (2.6%). The median duration of bevacizumab exposure was four cycles (range 1-30) when ADRs occurred. In 18 cases of death directly caused by ADRs, 50% occurred after only one cycle. In cases of disability, 40% of ADRs were neurologic: neuropathy, paralysis, and paresis.
CONCLUSION: To the best of our knowledge, this is the first analysis of bevacizumab safety profile using data collected in a national pharmacovigilance database. Our study confirms the frequency and seriousness of gastrointestinal, thromboembolic, and hemorrhage events with bevacizumab use and provides a picture of the bevacizumab safety profile in daily medical practice, despite intrinsic limitations.

Apixaban: an Oral Direct Factor-Xa Inhibitor.

Apixaban is a highly selective, reversible, direct factor Xa inhibitor that inhibits both free factor Xa and prothrombinase activity, and clot-bound factor Xa activity. A predictable pharmacokinetic profile, multiple pathways of elimination, an improved bleeding profile relative to warfarin with a lack of other significant adverse events, and no need for routine anticoagulation monitoring make apixaban appealing.
Apixaban is currently approved for venous thromboembolism (VTE) prophylaxis in total hip replacement and total knee replacement in Europe, Brazil, Australia, and New Zealand, and has been pre-approved in Indonesia and the Philippines. Completed phase 3 trials suggest that apixaban has promise as an alternative to aspirin and warfarin for prevention of stroke and systemic embolism in patients with atrial fibrillation.
Results of a large phase 3 trial were the first to show a survival benefit for this new class of oral anticoagulants in patients with atrial fibrillation. In patients with acute coronary syndrome, apixaban added to dual antiplatelet therapy with aspirin and clopidogrel resulted in unacceptably high rates of major bleeding. In medically ill patients, an extended course of thromboprophylaxis with apixaban was not superior to a shorter course with enoxaparin, and was associated with significantly more major bleeding events than enoxaparin.
Ongoing phase 3 trials will provide data regarding the efficacy and safety of apixaban for treatment of acute deep vein thrombosis and pulmonary embolism.

Search

Search