Gender-Based Differences in Hemostatic Responses. Implications in Effective Anticoagulant Management.

Abstract 2103

Poster Board II-80

Abstract: Recent reports from the National Heart, Lung and Blood Institute indicate that as many as 3 million women (particularly young) in the United States suffer from a form of heart disease fundamentally different from that in men, characterized by more even plaque development inside major and smaller blood vessels, posing diagnostic and treatment challenges leading to increased morbidity and mortality. It is hypothesized that women have variable but attenuated hemostatic responses to anticoagulant drugs when compared to men. In order to validate this hypothesis the hemostatic responses in healthy males (n=10) and females (n=10) were evaluated by performing the global clotting assays, fibrinokinetic assays and thrombin generation assays in the presence of Rivaroxaban, an oral Factor Xa inhibitor likely to replace warfarin, Enoxaparin, a low molecular weight heparin and saline as a control. Blood (20 ml) was drawn from healthy volunteers, males (n=10) and females (n=10) and placed into citrated tubes with one part of 3.2% sodium citrate to 9 parts of blood. The citrated whole blood was supplemented with Rivaroxaban (FC=0.3mg/ml), Enoxaparin (FC=5mg/ml) and saline as a control. The samples were analyzed to determine the whole blood APTT and Heptest clotting assays. The remaining citrated blood was centrifuged at 3000 rpm to obtain platelet poor plasma that was aliquoted and kept frozen at -70°C until further analysis. The plasma was then thawed and supplemented with saline, rivaroxaban (FC=0.3mg/ml) and Enoxaparin (FC=5mg/ml). A statistically significant difference between males and females was noted in APTT (p=0.0442)) and Heptest (p=0.0345) assays in the saline control values. However, the anticoagulant response to supplementation of the plasma samples with rivaroxaban at a final concentration of 0.3ug/ml and Enoxaparin at 5 ug/ml showed a statistically significant difference between males and females in the Heptest (P=0.0423) while the APTT assay felt a little short of statistical significance (P=0.0511).

Fibrinokinetics was performed and absorbance recorded (405 nm) at every minute for the next 30 minutes. There are gender-based differences in fibrinokinetic responses to anticoagulant drugs with females showing faster fibrin formation than males. The attenuated hemostatic responses observed in women compared to men may interfere in achieving adequate and effective anticoagulation leading to thrombotic complications.