Thrombosis and haemostasis
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Diagnostic management of suspected pulmonary embolism (PE) in patients with a history of venous thromboembolism (VTE) is complicated due to persistent abnormal D-dimer levels, residual embolic obstruction and higher clinical prediction rule (CPR) scores. We aimed to evaluate the safety and efficiency of the standard diagnostic algorithm consisting of a CPR, D-dimer test and computed tomography pulmonary angiography (CTPA) in this specific patient category. We performed a systematic literature search for prospective studies evaluating a diagnostic algorithm in consecutive patients with clinically suspected PE and a history of VTE. ⋯ In only 217 patients (15 %; 95 %CI 11-20) PE could be excluded without CTPA. The three-month VTE incidence rate was 0.8 % (95 %CI 0.06-2.4) in patients managed without CTPA, 1.6 % (95 %CI 0.3-4.0) in patients in whom PE was excluded by CTPA and 1.4 % (95 %CI 0.6-2.7) overall. In the pooled studies, PE was safely excluded in patients with a history of VTE based on a CPR followed by a D-dimer test and/or CTPA, although the efficiency of the algorithm is relatively low compared to patients without a history of VTE.
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Within the past decade, high on-treatment platelet reactivity (HTPR) on clopidogrel and its clinical implications have been frequently discussed. Although it has been previously assumed that HTPR is a phenomenon occurring only in patients treated with clopidogrel, recent data show that HTPR might also occur during treatment with prasugrel or ticagrelor in the acute phase of ST-elevation myocardial infarction. Moreover, it has been postulated that there is a therapeutic window for P2Y12 receptor blockers, thus indicating that HTPR is associated with thrombotic events whereas low on-treatment platelet reactivity (LTPR) is associated with bleeding events. ⋯ The majority of recent clinical randomised trials have not supported the hypothesis that platelet function testing and tailored antiplatelet therapy are providing a favourable clinical outcome. These trials, mainly performed in low-to-moderate risk patients, will be reviewed and discussed. Finally, an algorithm based on current knowledge is suggested, which might be of use for design of clinical trials.
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Von Willebrand disease (VWD), the most common genetic bleeding disorder, is characterised by a quantitative or qualitative defect of von Willebrand factor (VWF). Patients with VWD suffer from mucocutaneous bleeding, of severity usually proportional to the degree of VWF defect. In particular, gastrointestinal bleeding associated with angiodysplasia is often a severe symptom of difficult management. This review focuses on the pathophysiology, diagnosis and treatment of VWD-associated gastrointestinal angiodysplasia and related bleeding.
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The clinical penetrance of venous thromboembolism (VTE) susceptibility genes is variable, being lower in heterozygous carriers of factor V Leiden and prothrombin 20210A (mild thrombophilia), and higher in the rare carriers of deficiencies of antithrombin, protein C or S, and those with multiple or homozygous abnormalities (high-risk thrombophilia). The absolute risk of VTE is low, and the utility of laboratory investigation for inherited thrombophilia in patients with VTE and their asymptomatic relatives has been largely debated, leading to the production of several Guidelines from Scientific Societies and Working Groups. The risk for VTE largely depends on the family history of VTE. ⋯ The identification of the asymptomatic carrier relatives of the probands with VTE and thrombophilia could reduce cases of provoked VTE, offering them primary antithrombotic prophylaxis during risk situations. In most guidelines, this is considered justified only for relatives of probands with a deficiency of natural anticoagulants or multiple abnormalities. Counselling the asymptomatic female relatives of individuals with VTE and/or thrombophilia before pregnancy or the prescription of hormonal treatments should be administered with consideration of the risk driven by the type of thrombophilia and the family history of VTE.
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Review Practice Guideline
General mechanisms of coagulation and targets of anticoagulants (Section I). Position Paper of the ESC Working Group on Thrombosis--Task Force on Anticoagulants in Heart Disease.
Contrary to previous models based on plasma, coagulation processes are currently believed to be mostly cell surface-based, including three overlapping phases: initiation, when tissue factor-expressing cells and microparticles are exposed to plasma; amplification, whereby small amounts of thrombin induce platelet activation and aggregation, and promote activation of factors (F)V, FVIII and FXI on platelet surfaces; and propagation, in which the Xase (tenase) and prothrombinase complexes are formed, producing a burst of thrombin and the cleavage of fibrinogen to fibrin. Thrombin exerts a number of additional biological actions, including platelet activation, amplification and self-inhibition of coagulation, clot stabilisation and anti-fibrinolysis, in processes occurring in the proximity of vessel injury, tightly regulated by a series of inhibitory mechanisms. "Classical" anticoagulants, including heparin and vitamin K antagonists, typically target multiple coagulation steps. A number of new anticoagulants, already developed or under development, target specific steps in the process, inhibiting a single coagulation factor or mimicking natural coagulation inhibitors.