Thrombosis research
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Thrombosis research · Oct 2012
ReviewMicroparticles in vascular disorders: how tissue factor-exposing vesicles contribute to pathology and physiology.
Coagulation is initiated by tissue factor (TF). Coagulant TF is constitutively expressed by extravascular cells, but there is increasing evidence that TF can also be present within the blood, in particular during pathological conditions. ⋯ Remarkably, high levels of coagulant TF-exposing vesicles are present in other body fluids such as saliva and urine of healthy persons, suggesting that these vesicles play a physiological role. We postulate that the presence of TF-exposing vesicles in body fluids as saliva and urine provides an additional source of coagulant TF that promotes coagulation, thereby reducing blood loss and contributing to host defence by reducing the risk of microorganisms entering the "milieu intérieur".
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Orally active direct inhibitors of thrombin and factor Xa have now been approved for treatment or prevention of deep vein thrombosis,and stroke associated with atrial fibrillation. The factor Xa inhibitor, rivaroxaban, has shown promising results in the treatment of acute coronary syndrome but is not yet approved for that indication. ⋯ These agents have fewer drug interactions than warfarin, have a predictable clearance, and hence do not require monitoring. Patients with renal insufficiency have delayed clearance and hence may have elevated levels of the drug leading to increased risk of bleeding.
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Despite improved clinical outcomes from dual anti-platelet therapy with aspirin plus the CYP12 ADP receptor antagonist clopidogrel in patients undergoing coronary revascularisation, ex-vivo platelet function testing consistently reveals a proportion of patients with apparent resistance or non-response to clopidogrel loading and maintenance therapy who are at increased risk of coronary thrombosis. Treatment regimens using the newer CYP12 antagonists prasugrel and ticagrelor demonstrate improved ex-vivo platelet inhibition and superior clinical efficacy in large-scale clinical trials-even in patients demonstrating clopidogrel resistance. ⋯ Therefore when deciding anti-platelet regimens in suspected acute coronary syndrome, particular consideration must be given to patient's risk of thrombosis (STEMI, previous stent thrombosis), the procedure (complex PCI, thrombus in-situ, strategy of pre-treatment), and factors affecting safety (patient age, patient weight, previous stroke, liklehood of surgical revascularisation). Placing the focus on individualised patient risk-benefit assessment with appropriate use of platelet function testing when indicated, in combination with the ongoing assessment of prasugrel and ticagrelor in larger numbers of patients should be the key strategies governing use of dual anti-platelet therapy.
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Thrombosis research · Oct 2012
Clinical TrialPeri-procedural bridging with low molecular weight heparin in patients receiving warfarin for venous thromboembolism: a pediatric experience.
The incidence of venous thromboembolism (VTE) in children appears to be increasing, and warfarin remains one of the few standard anticoagulants used for secondary VTE prevention. When invasive procedures are required in adults with high TE risk who are receiving warfarin, low-molecular weight heparin (LMWH) bridging is recommended, based mainly upon observational evidence; in children, no such studies have been published. We sought to determine the risks of recurrent TE (both VTE and arterial TE [ATE]) and major bleeding with peri-procedural LMWH bridging in children receiving warfarin for VTE. ⋯ This study provides important preliminary data on safety and efficacy of perioperative LMWH bridging for adolescent VTE patients receiving warfarin. Larger collaborative pediatric studies are warranted to substantiate these findings and to investigate prognostic factors of bleeding and recurrent TE in this setting.
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Thrombosis research · Oct 2012
Should we follow the 9th ACCP guidelines for VTE prevention in surgical patients?
The 9th edition of the American College of Chest Physicians (ACCP) guidelines on antithrombotic therapy and prevention, includes relevant changes compared to previous versions. In the 9th ACCP, leadership of most chapters was given to methodologists who were familiar with the GRADE methodology. All topic panelists underwent a selection process paying particular attention to their financial and intellectual conflicts of interests. ⋯ A controversial modification in orthopedic patients is recommendation in favor of the use of aspirin after hip or knee arthroplasty. New oral anticoagulants are recommended, but LMWH are suggested as the preferred option. Extending pharmacological prophylaxis for up to 35days rather than 10-14days is now suggested for patients undergoing major orthopedic surgery.