Abstract
Hemophilia A and hemophilia B are hereditary X-linked disorders of blood coagulation caused by a deficiency of factor (F) VIII or FIX, respectively. Affected males suffer from joint and muscle bleeds and other serious internal bleeding, the severity of which is correlated with the level of the coagulation protein in their blood. Early diagnosis and cloffing factor (CF) replacement therapy has remarkably improved the outlook of patients with hemophilia, so that they can live near normal lives. However, major issues such as compliance due to need for frequent venous access and treatment failure due to development of alloantibody (inhibitors) to the replaced factor remain. Furthermore, due to cost and availability of CF3, state of the art care is inaccessible to a vast majority of patients in developing countries. Molecular genetic studies of the FVIII and FIX genes have not only allowed better understanding of the disease and its diagnosis but also led to the development of recombinant therapeutic products as well as gene therapy. Genetic evaluation is also becoming increasingly important for predicting the development of inhibitors, apart from carrier detection and genetic counseling.
Highlights
Blood clotting is a host defence mechanism that in parallel with the inflammatory responses helps protect the integrity of the vascular system and promotes repair after tissue injury
Plasma FVIII or FIX inhibitor activity is assessed at regular intervals in patients who are receiving replacement therapy or if there is lack of response to it
One Bethesda unit is the amount of inhibitor that will neutralize 50% of a given factor activity in normal plasma after a defined period of incubation [74]. While these clotting time based assays have been very useful for the diagnosis of hemophilia, they have not been able to discriminate the clinical heterogeneity of symptoms in those with severe disease
Summary
Blood clotting is a host defence mechanism that in parallel with the inflammatory responses helps protect the integrity of the vascular system and promotes repair after tissue injury This process involves a series of orderly steps involving components of the vasculature, platelets (primary hemostasis) and coagulation proteins (secondary hemostasis) that leads to the formation of platelet plug and culminates in the formation of a stable fibrin clot. Congenital defects of platelets or plasma proteins involved in this process generally lead to bleeding disorders [1,2] In some of these disorders, patients with severe disease are prone to spontaneous bleeds with critical consequences. This article will describe the clinical and diagnostic aspects of hemophilia and discuss how the knowledge of molecular genetics of FVIII/FIX has contributed to improved patient care
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