of 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,2 plasma 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 investigators4-9 who 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 this problem a large series of such carriers was studied.
Materials and MethodsVenous blood for clotting times was taken from the second of two siliconed syringes, the first being delivered into various appropriate anticoagulants.10 Glass and silicone clotting time, prothrombin consumption, and AHF and PTC assays were per¬ formed as previously described.10 Two-hour pro¬ thrombin consumption was performed following Dreskin'su modification of Quick's u original de¬ scription, except that blood used as the source of serum was incubated at 37 C for two hours rather than one hour following collection. It is referred to in the text as the "two-hour serum prothrombin time" method. Thromboplastin generation was modified from Biggs and Douglas,13 with use of equal volumes of 1 :5 dilution of BaSO*-adsorbed plasma, 1 :10 dilution of serum, and a suspension of platelets10 whose concentration approximates that in whole blood. Thromboplastin generation, with use of all three components from the carrier, was performed in 13 carriers, but the range of results was wide, as might be expected from the nonspecificity of the test. Therefore, the test was then performed, in the case of hemophilia A carriers, with use of the carrier's BaSOi-adsorbed plasma and normal serum and platelets, and in the case of hemophilia carriers, with use of the carrier's serum and normal BaSOi-adsorbed plasma and platelets. Thus the method becomes an assay for AHF and PTC, respectively, as long as proaccelerin and proconvertin (Stuart), respectively, are normal in the carriers, and this was found to be the case by appropriate one-stage assays. This method is referred to in the text as "thrombo¬ plastin generation assay" for AHF or PTC.The normal distribution for results in the various tests was calculated from observations in 75 male and 25 female healthy medical students and tech¬ nicians in Pittsburgh and Chapel Hill, except in the case of the thromboplastin generation and two-hour serum prothrombin time methods, where 25 Pittsburgh males and females were the normal group. No difference based on sex or geog...