The laboratory diagnosis of the carrier state for classic hemophilia

Abstract

Estimation of the titer of procoagulant antihemophilic factor (AHF) and the concentration of AHF-like antigens, as detected by heterologous antiserum, provides a method for diagnosis of the carrier state of classic hemophilia. Among 87 obligate carriers, 82, or 94%, could be identified as carriers by logarithmic discriminant analysis because the titer of procoagulant AHF was disproportionately lower than the concentration of AHF-like antigens relative to normal women. Women who were the mothers of individuals with isolated cases of hemophilia appeared to be carriers in at least 85% of cases, suggesting that the frequency of cases due to fresh mutations is low. The validity of the techniques used is supported by the frequency with which the carrier state was recognized in daughters of hemophiliacs who themselves had no sons. Corrected for the known error of the method, 48% of 75 such daughters appeared to be carriers, not significantly different from their anticipated chance of 50%.