Thrombosis research
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Congenital dysfibrinogenemia and hypofibrinogenemia are rare diseases characterized by inherited abnormality in the fibrinogen molecule, resulting in functional defects (dysfibrinogenemia) or low fibrinogen plasma levels (hypofibrinogenemia). ⋯ Both mutations cause conformational changes in fibrinogen, which lead either to impaired fibrinogen assembly (fibrinogen Hranice) or abnormal fibrinogen function (fibrinogen Praha IV).
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Thrombosis research · Oct 2014
Padua prediction score and thrombin generation in hospitalized medical patients.
The Padua prediction score is a risk assessment model used to identify medical patients at high risk for venous thromboembolim (VTE).We aimed to assess the relationship between the severity of Padua score and thrombin generation as a measure of overall thrombotic activity. ⋯ Single thrombin generation measurement obtained at the same time in acutely hospitalized patients didn't bear any correlation with the Padua prediction score. This finding should be interpreted with caution considering the underrepresentation of risk factors that may influence thrombin generation.
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Edoxaban is an oral, once-daily direct factor Xa (FXa) inhibitor. Although rapidly cleared, strategies to reverse edoxaban-mediated effects on anticoagulation are needed in cases of excessive bleeding or emergency. This study evaluated the effect of two prohemostatic agents, recombinant factor VIIa (rFVIIa) and factor VIII inhibitor bypass activity (FEIBA), on the anticoagulatory effects of supratherapeutic concentrations of edoxaban in human whole blood ex vivo. ⋯ The findings of this ex vivo study suggest that rFVIIa and FEIBA rapidly reversed edoxaban-mediated anticoagulation effects based on PT and aPTT, but had minimal effect based on intrinsic FX activity. No dose response was observed for rFVIIa or FEIBA.
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Thrombosis research · Oct 2014
Platelet activation biomarkers in Berkeley sickle cell mice and the response to prasugrel.
Vaso-occlusive crisis (VOC) is a common complication that occurs in sickle cell disease (SCD) patients. Although underlying mechanisms of VOC remain unclear, platelet activation has been associated with VOC. In the present study, plasma adenine nucleotide measurements using LC-ESI-MS/MS showed that plasma ADP in the Berkeley murine model of SCD was significantly higher (applox. 2.7-fold increase) compared with control mice. ⋯ Oral administration of prasugrel effectively inhibited ex vivo platelet activation consistent with clinical data in patients with SCD. In conclusion, in the Berkeley murine model of SCD, we found evidence of basal and agonist-stimulated platelet activation which could in part be attenuated by prasugrel. These data are consistent with observations made in patients with SCD and suggest possible utility of this murine model and prasugrel therapy in exploring treatment options for patients with SCD.