Molecular Defects in Hemophilia A
Hemophilia A, classic hemophilia, is an X chromosomc-linked inherited coagulation disorder characterized by deficient factor VIII activity. Clinically, and when characterized by procoagulant or immunologic assays, it is a heterogeneous disorder. However, disease severity usually corresponds to the extent of factor VIII deficiency.1 Severe hemophilia with recurrent hemarthroses usually means that there is no detectable plasma factor VIII (< 1% of normal factor VIII activity). Individuals with 1–5% of normal factor VIII levels tend to have moderately severe disease, with most bleeding episodes due to trauma. Mild hemophilia (6–25% of normal factor VIII activity) may only be detected when excessive bleeding occurs during surgery or after severe injuries. Nonfunctional, immunoreactive factor VIII-like protein, at levels comparable to those in normal plasma, is detected in 10% of plasmas from patients with mild or moderate hemophilia A.2, 3 In addition, low levels of factor VIII antigen (1–10% of those in normal plasma) can be detected by sensitive immunoassays in the plasma of 20% of patients with severe hemophilia A.4 The basis for this heterogeneity has been clarified by recent studies that have examined the molecular basis for the factor VIII deficiency in families with hemophilia.
KeywordsFactor Viii Factor Viii Activity Severe Hemophilia Deficient Factor Viii Factor Viii Gene
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