Thrombosis research
-
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.
-
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.
-
Thrombosis research · May 2014
ReviewDeveloping individualized coagulation profiling of disease risk: thrombin generation dynamic models of the pro and anticoagulant balance.
Global assays and computational models have advanced research into the realm of individualized profiling of hemostatic states. This brief review will describe one computational approach which utilizes an integrated method that evaluates the dynamics of thrombin generation by defining interactions of the pro and anticoagulant proteins, enzymes and cofactors based upon individualized concentrations of select factors. This plasma composition based computational modeling can provide a mechanism based bridge between empirical global assays of coagulation and individualized risk prediction.
-
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.
-
Thrombosis research · May 2014
ReviewAdvances in the diagnosis and management of acute pulmonary embolism.
The diagnostic management of acute pulmonary embolism (PE) is complicated by its heterogeneous clinical presentation. Current diagnostic algorithms, combining clinical probability estimation with D-dimer testing and imaging tests, are very safe to exclude PE, although at costs of high numbers of CT-examinations. In view of cost- and time-saving as well as safety issues, several attempts have recently been undertaken to reduce the number of required imaging tests. ⋯ Risk stratification of hemodynamically stable PE patients with use of clinical decision rules, cardiac biomarkers or imaging tests, aids physicians in determining the most appropriate treatment approach for the individual patient. This is essential to differentiate patients at low risk of adverse outcome, who may be safely treated at home, from intermediate-risk patients, who require closer monitoring and for whom recent studies have evaluated the efficacy and safety of systemic thrombolytic therapy. This article reviews recent advances and challenges that remain in the diagnostic work-up and initial management of acute, clinically stable PE.