Hemostatic data in relatives of hemophiliacs A and B; evidence for modifying the classical sex-linked recessive hypothesis.

Abstract

In 1803, Dr. John C. Otto,1of Philadelphia, reported observations on a familial hemorrhagic disorder affecting only males but transmissable via some of the unaffected females. Otto's observations undoubtedly concerned patients whom we now speak of as having hemophilia A (classical hemophilia, antihemophilic factor [AHF] deficiency) or hemophilia B (Christmas disease,2plasma thromboplastin component [PTC] deficiency3), the genetics of these two disorders being apparently identical. Thus the term sex-linked recessive has been applied to both conditions, and by and large the female carrier or heterozygote in such families is asymptomatic and undetectable by most laboratory tests. However, the data of a number of investigators4-9who have studied a few such carriers by means of recently developed tests suggest that the carrier state is attended in some cases with both clinical and laboratory manifestations of a mild hemorrhagic disorder. In an attempt to shed further light on