Bleeding Tendency of Carriers of Hemophilia A — Dependent on the Age of the Carriers?

Abstract

Carriers of hemophilia A often present with normal clotting factor VIII levels but occasionally also report a considerable tendency to bleeding. Recently it was shown that reduced concentrations of factor VIII and IX in carriers of hemophilia A and B are associated with favorable effects on blood coagulation and hemostasis which contributes to cardiovascular protection and a decreased mortality of ischemic heart disease. [1] Hemophilia A is an X-linked recessive bleeding disorder of variable severity that is caused by a deficiency of factor VIII (FVIII). The disease results from mutations in the FVIII gene which are heterogeneous both in type and position within the gene. The frequency of hemophilia A is 1–2 in 10 000 male births in all ethnic groups. Because carriers have usually one unaffected allele the FVIII concentration is often of about 50 % of normal. But symptomatic carriers of hemophilia A can present with bleeding symptoms like a male patient with mild hemophilia A. A small number of carriers may have very low levels of FVIII [2] due to co-inheritance of a variant von Willebrand factor allele (i.e. von Willebrand’s disease Normandy), homozygosity for hemophilia gene [3] or extreme lyonization. The daughters of men with hemophilia are obligate carriers and carriers have a 50:50 chance of passing on the condition to a son and a 50:50 chance that a daughter will be a carrier. Members of the same family usually have the same FVIII level and the severity