Evaluation of the determinants and characterization of bleeding in hemophilia A and B carriers
Hemophilia A and B are bleeding disorders caused by a deficiency in coagulation factor VIII (FVIII) or coagulation factor IX (FIX), respectively. Due to the X-linked inheritance pattern, males are affected with the disease, while females are almost exclusively carriers of hemophilia. Although carriers were historically assumed to be asymptomatic, it is now known that many hemophilia carriers experience abnormal bleeding. Hemophilia carriers have higher bleeding scores compared to controls and have decreased health related quality of life. Despite this recognition, little is understood concerning the cause of this bleeding. As such, this study aims to evaluate hemophilia carrier bleeding to elucidate the cause of the abnormal bleeding phenotype. The objectives of this study are to evaluate hemophilia carrier bleeding in several contexts and with respect to numerous determinants of bleeding in order to elucidate the relative contribution of each determinant to the Self-administered Bleeding Assessment Tool (Self-BAT) bleeding score, and to examine the underlying pathophysiological mechanism of abnormal bleeding in hemophilia A carriers by comparing the response to desmopressin in hemophilia A carriers and controls. This study demonstrates that hemophilia carriers experience comparable levels of bleeding as women with other bleeding disorders and that there may be differences in the manifestation of bleeding between hemophilia A and B carriers. Importantly, we also demonstrate that increasing age, O-type blood, and low factor level may contribute to an abnormal bleeding phenotype in carriers. Additionally, we show that hemophilia A carriers, even with normal baseline FVIII levels, have a significantly reduced and less sustained FVIII responses to DDAVP compared to controls. To our knowledge, this is the first study to examine multiple determinants of bleeding in hemophilia carriers in a single study and the first to fully characterize the response to DDAVP in hemophilia A carriers compared to controls. In conclusion, these results have begun to elucidate the cause of hemophilia carrier bleeding. Ultimately, an improved understanding of what factors put a carrier at risk of abnormal bleeding and of the mechanism of this abnormal bleeding will allow for improved healthcare and quality of life for these women.
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