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The clinical phenotype in hemophilia generally correlates with the type of mutations. We studied 16 patients with severe hemophilia A (factor VIII and factor VIII:Ag &lt;1%) with intron 22 inversions of the factor VIII gene and 6 patients with hemophilia B, 2 each having a common mutation, for the common prothrombotic markers in the anticoagulant and fibrinolytic cascade. Of the patients, 6 of 10 with "clinically mild" and 1 of 12 with "clinically severe" disease had a deficiency or abnormality of any of the factors studied. Thrombophilia thus modulates the clinical severity of hemophilia as is observed in patients who carry similar mutations.

Reduced Clinical Severity in a Mutationally Well-Characterized Cohort of Severe Hemophilia With Associated Thrombophilia