Hemophilia - NCBI

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Refer to: Kasper CK, Parton L: Reproduction in hemophilia. ... sex-linked trait is well known. Given the serious- .... differs from that in the general United States.
THE WES:TERN ;Journal of Medicine Refer to: Kasper CK, Parton L: Reproduction in hemophilia. West J Med 120:273-277, Apr 1974

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Hemophilia CAROL K. KASPER, MD LANCE PARTON, BS Los Angeles

THE MODE OF INHERITANCE of hemophilia as a sex-linked trait is well known. Given the seriousness of the disease, the suffering and expense for the patient and his family, and the expense to society through subsidized benefits, one might assume that those persons at great risk of transmitting the defective gene would refrain from parenthood. Such an assumption would be naive. Discombel warned that society might soon bear sharply increased burdens because persons with hemophilia and other serious but treatable sexlinked or dominant genetic disorders were surviving to adulthood and having children, thereby rapidly increasing the number of affected persons in the population. His comments were angrily attacked in three London newspapers2-4 by the Haemophilia Society. Members of that society argued that the decision to have children was entirely the private affair of the individual and pointed out that many hemophiliacs felt that they themselves had weathered the disease well enough, and so should their hemophiliac descendants. The treatment for hemophilia has become far From the Department of Medicine, University of Southern California School of Medicine, and Orthopaedic Hospital, Los Angeles. (The Orthopaedic Hospital is an International Hemophilia Training Center.) Supported in part by Social and Rehabilitative Services. DHEW, Grant RT 18.

Reprint requests to: C. K. Kasper, MD, 2400 South Flower Street, Los Angeles, CA 90007.

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 19501954 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. THE WESTERN JOURNAL OF MEDICINE

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more effective and convenient in the last decade with the introduction of clotting-factor concentrates and home infusion programs. The cost of treating the disease, an average of $5,000 per patient per year in Southern California, is now being borne more by government agencies or large group-insurance plans than by the individual family. The burden on the patient and family, though still great, has lessened. We wondered whether the improved chances for the survival and well-being of hemophiliacs has led to a greater willingness to transmit the defect, and we had access to an unusually large group of hemophiliacs who were registered for care at Orthopaedic Hospital. We determined the number of children sired by hemophiliacs and the number born to women who have already had at least one hemophiliac son, and attempted to make comparisons with birthrates of the general population of the United States.

Methods Family histories were obtained by personal interview from nearly all the patients with severe hemophilia registered at Orthopaedic Hospital as of 1971. Of these patients, 193 had severe hemophilia A and 57 had severe hemophilia B. As a part of the routine examination, information was obtained about the patient's birthdate, marital status, the birthdates and sex of his children, the birthdates and sex of his siblings (living and dead), the birthdate of his mother, the presence of hemophilia in any other relative, and the religion of the family. Patients were excluded from the survey only if no useful information was available. For example, adopted hemophiliac children were not included if we had no information about their biologic relatives. The incidence of hemophilia appears to be similar in all racial, ethnic, religious and socioeconomic groups. The care of hemophiliacs in Southern California is heavily concentrated at Orthopaedic Hospital, with no obvious intentional or unintentional selection for or against any population group. Patients from rural and urban areas are proportionally represented. We feel that the study group is a fair sample of the general Southern California population with regard to these characteristics. For the purposes of the study, we have compared the study group to the general United States population despite the realization that the proportion of certain ethnic groups, notably Mexican-Americans, in Southern California 274

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differs from that in the general United States population. Vital statistics publications of the federal Public Health Service provided data on the incidence of marriage by American males and birthrates for American women through the years 1940-1968, and data on the numbers of children sired by American men for most years from 1940 through 1966. In order to compare our statistics on the number of children sired by hemophiliacs, and the number born to mothers of hemophiliacs, with the available information about the general United States population, we made the following tallies. We counted the number of hemophiliac men alive each year from 1940 through 1944, 1950 through 1954, and 1960 through 1964 and grouped this information according to their ages within the range of 15 to 44 years. We then counted the number of children sired by these men in each age and calendar-year category. From the vital statistics tables, we calculated the number of children which would have been expected for an equal number of men of the general population in each age and calendar-year category. We also counted the number of mothers of hemophiliacs alive in each year from 1940 through 1968 and grouped this information according to their ages within a selected range of 20 to 39 years and according to their parity within a selected range of one to four. Then we counted the number of births to these women in each age, parity and calendar-year category. From the vital statistics tables we calculated the number of births which would have been expected of an equal number of women of the general population in each age, parity and calendar-year category. The observed incidence of children sired by hemophiliacs and of children born to mothers of hemophiliacs was compared with the expected incidence of births, based on the vital statistics data, by means of chi-square tests.

Results Hemophiliac Men In Table 1 the actual incidence of marriage by hemophiliac men is compared with that expected for equal numbers of age-matched men of the general population of the United States for the year 1968. This is the most recent year for which vital statistics are available. At that time, 58 percent of hemophiliacs 20 years old or older and 75

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percent of hemophiliacs 30 years old or older were married. The over-all incidence of marriage by hemophiliacs was 82 percent of that expected for age-matched males of the country's population in general. As of 1971, 81 married hemophiliacs had a total of 130 children, of whom 59 were daughters. Of these obligatory carriers, 27 were in the childbearing ages of 15 to 34 years old and 32 were younger than 15 years old. Married hemophiliacs born before 1940 had an average of 2.1 children each as of 1971. In Table 2 we compare the numbers of children sired by hemophiliacs (married and unmarried)

in the years 1940 to 1944, 1950 to 1954 and 1960 to 1964 with those expected for an equal number of age-matched men of the general United States population. The number of children sired by hemophiliacs was 80 percent of that for the general male population in the years 1940-1944 (an insignificant difference). However, from 1950 to 1954 and 1960 to 1964 the numbers of children were 25 and 38 percent, respectively, of those expected for the general population (a significant difference). In the latter two periods the difference between actual and expected numbers of children was most significant (p =