Statistical study of genotype assignment (carrier detection) in hemophilia B.
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Biomedical subjects
Publications and source records attributed to C K Kasper.
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Factor VIII inhibitor levels were measured on 261 occasions in 76 hemophilia-A inhibitor patients before and after prothrombin complex concentrate infusion at 13 treatment centers. A rise in inhibitor level to at least twice the pretreatment value occurred in 35 treatment episodes (13.5%), in 27 patients (36%). In 16 patients (21%), such an anamnestic immune response occurred with the first treatment. Factors predisposing to anamnestic responses may include patient idiosyncrasy, low pretreatment inhibitor levels, and exposure to concentrate over several days.
Variations of the partial thromboplastin time (PTT) were tested to determine the best screening method for detection of inhibitors of factor VIII. Variables tested included the duration of preincubation of a mixture of patient plasma and factor VIII source (normal plasma), the ratio of the patient plasma to the normal plasma, and the duration of incubation of the normal plasma-patient plasma mixture with kaolin-cephalin suspension prior to recalcification. The following conclusions were reached: (1) The PTT performed on a mixture of equal amounts of patient and normal plasma without preincubation of the mixture was inadequate to detect many factor VIII inhibitors. (2) Factor VIII inhibitors of more than 0.5 Bethesda units could be detected if the PTT was performed on a mixture of four parts patient plasma and one part normal plasma, with preincubation of the mixture for 60 min at 37 degrees C. (3) Factor VIII inhibitors as weak as 0.1 Bethesda units could be detected if the PTT was performed on a mixture of four parts patient plasma and one part normal plasma incubated with kaolin-cephalin suspension for 120 min at 37 degrees C before recalcification. The last method may make detection of mild factor VIII inhibitors possible in routine clinical laboratories not equipped to perform the more technically difficult Bethesda inhibitor assays.
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Patterns of marriage and parenthood were studied in the families of 250 patients with severe hemophilia. The incidence of marriage among adult hemophiliacs was 82.5 percent that of age-matched males of the general United States population, as of 1968. Married hemophiliacs 30 years old or older had an average of 2.1 children each, as of 1971. In the periods 1950-1954 and 1960-1964, the numbers of children sired by hemophiliacs were 25 and 38 percent, respectively, of the numbers expected of age-matched men of the general United States population. This indicates a lesser ability or willingness to have children. The number of additional births to women who were already mothers of hemophiliacs was compared with that expected for women of the general population of the United States, matched for age and parity. In the years 1940 through 1954, the birthrates for the two groups were similar. However, in the years 1955-1968, the birthrate among carriers declined more rapidly than that in the general population. The improved medical treatment of hemophilia has apparently not resulted in a greater willingness of affected persons to transmit the defective gene.
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