Thrombosis research
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Thrombosis research · May 2014
Case ReportsFGB mutations leading to congenital quantitative fibrinogen deficiencies: an update and report of four novel mutations.
Causative mutations leading to congenital quantitative fibrinogen are frequently clustered in FGA encoding the fibrinogen Aα-chain. Mutations of FGB encoding the Bβ-chain are less common and of interest since the Bβ-chain is considered the rate-limiting factor in the hepatic production of the fibrinogen hexamer. ⋯ The continuous characterization of novel molecular defects responsible for fibrinogen deficiency combined with modelling of mutant proteins will continue to provide a better comprehension of the complexity of fibrinogen synthesis and physiology.
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Thrombosis research · May 2014
ReviewReversal of new, factor-specific oral anticoagulants by rFVIIa, prothrombin complex concentrate and activated prothrombin complex concentrate: a review of animal and human studies.
Recombinant activated factor VII (rFVIIa), prothrombin complex concentrate (PCC) and activated PCC (aPCC) are three non-specific haemostatic agents sometimes employed to reverse new, factor-specific oral anticoagulants. ⋯ While preclinical studies may hint at a role for these haemostatic agents in reversing the anticoagulant effects of oral, factor-specific anticoagulants, existing trials offer inconclusive evidence to guide a clinical decision among individual agents with respect to potency and thrombosis risk. The mechanistic differences of these hemostatic agents in terms of their interactions with other coagulation factors impose major obstacles for the scientists using animal models to compare the efficacy of these reversal agents.
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Thrombosis research · May 2014
ReviewCrosstalk between the coagulation and complement systems in sepsis.
Sepsis is a potent activator of the hemostatic and complement systems. While local activation of these proteolytic cascades contributes to the host defense, their uncontrolled systemic activation has major tissue damaging effects that lead to multiple organ failure and death. ⋯ We applied a potent C3 convertase inhibitor, compstatin, which prevented sepsis-induced complement activation, reduced thrombocytopenia, decreased the coagulopathic responses, and preserving the endothelial anticoagulant properties. Overall, our work demonstrates that live bacteria and bacterial products activate the complement and coagulation cascades, and that blocking formation of complement activation products, especially during the organ failure stage of severe sepsis could be a potentially important therapeutic strategy.
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Thrombosis research · May 2014
The effects of recombinant activated factor VII dose on the incidence of thromboembolic events in patients with coagulopathic bleeding.
Previous studies have suggested the used of off-label recombinant factor VII (rFVIIa) increases the risk of thromboembolic events, but the effect of the dose of rFVIIa is not well described in the literature. ⋯ No significant difference in the incidence of thromboembolic events was seen between low dose versus high dose rFVIIa over a seven year period at our institution. However, due to the relatively low overall incidence and a small sample size, type II error may be present.
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Thrombosis research · May 2014
ReviewAbnormal adhesion of red blood cells in polycythemia vera: a prothrombotic effect?
Polycythemia vera (PV) is a myeloproliferative neoplasm (MPN) characterised by the V617F activating mutation in the tyrosine kinase JAK2. PV patients exhibit increased haemoglobin levels and red cell mass because of uncontrolled proliferation of the erythroid lineage. ⋯ An additional parameter that might contribute to this risk was recently brought to light by work from our group showing abnormal activation of adhesion proteins in PV RBCs. In this review we provide an overview of these recent findings and discuss how the pro-adhesive features of JAK2V617F-positive red blood cells might initiate and contribute to the circulatory complications described in PV.