A H Bröcker-Vriends

University of Amsterdam, Amsterdam, North Holland, Netherlands

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Publications (22)84.35 Total impact

  • [show abstract] [hide abstract]
    ABSTRACT: Mortality figures were calculated for a group of 717 Dutch haemophiliacs over the period 1973-86. Follow-up was on average 10.9 years; no patients were lost to follow-up. The data were compared to the general male population by actuarial methods and patient-year analysis. Forty-three patients died, while 20 deaths were expected in a hypothetical group of non-haemophiliacs of the same age distribution. Hence, overall mortality was 2.1 times higher than in the general population. This leads to a calculated life expectancy of 66 years, as compared to 74 years in the general male population. Mortality did not differ much by severity of haemophilia. A possibly beneficial effect of prophylaxis on longevity was observed. Haemorrhage occurred in half of all deaths and among these traumatic bleeding was the most prevalent. The number of deaths due to ischaemic heart disease was significantly lower (80% reduction) than expected and therefore the authors conclude that haemophilia offers protection against ischaemic heart disease. Cancer mortality was significantly higher (2.5 times) than expected.
    British Journal of Haematology 03/2008; 71(1):71 - 76. · 4.94 Impact Factor
  • I Varekamp, T P Suurmeijer, F R Rosendaal, A H Bröcker-Vriends
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    ABSTRACT: A retrospective study was performed to explore carrier testing among women who were possible or obligate carriers of the haemophilia gene. Knowledge of the possibility of carrier testing and use of carrier testing were studied separately. In our exploration we were guided by the diffusion theory and the Health Belief Model. Logistic regression analysis showed that four factors were statistically significant related to knowledge of carrier testing: information via mass media, a haemophilic relative in the nuclear family rather than in the extended family, medical severity of haemophilia, and information from the patients' organization. For those women acquainted with carrier testing two of the four factors just mentioned were significantly related to the utilization of carrier testing i.e. having a haemophilic relative in the nuclear family and the medical severity of the haemophilia. In addition the following factors were associated: attitude towards abortion because of haemophilia, educational level, and marital status. Notwithstanding the prominent function of the mass media and the patients' organization, the respondents themselves stated that relatives, especially parents and sisters, were the most important source of information on genetic counselling and carrier testing.
    Social Science [?] Medicine 10/1993; 37(5):639-48. · 2.73 Impact Factor
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    ABSTRACT: Developments in DNA technology have provided a novel means of carrier detection and prenatal diagnosis of hemophilia A and B. The collection of a large set of data has enabled us to evaluate the present feasibility and reliability of a diagnosis at the gene level and its contribution to methods already available. Since 1984, 533 potential and obligate carriers belonging to 170 families with hemophilia have been referred to us. By the combined use of pedigree analysis, coagulation assays, and DNA (RFLP) analysis, certainty about the carrier status has been markedly increased for the potential carriers. Although RFLP analysis revealed the possible origin of the mutation in many families with an isolated patient, uncertainty remained for quite a number of their female relatives because of the possible occurrence of germline mosaicism. Forty-one women requested prenatal diagnosis during one or more pregnancies. The short time interval between pregnancies, even after abortion of an affected fetus, proved that first-trimester prenatal diagnosis has become an acceptable option for women at risk. Recently, efficient methods for direct identification of mutations have been developed, and they may allow a definite diagnosis for all families with hemophilia in the near future.
    Annals of Hematology 02/1992; 64(1):2-11. · 2.87 Impact Factor
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    I Varekamp, T Suurmeijer, A Bröcker-Vriends, F R Rosendaal
    Birth defects original article series 02/1992; 28(1):139-48.
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    ABSTRACT: Coagulation and RFLP data from 41 families with an isolated haemophilia A patient were used to estimate the sex ratio of mutation frequencies (nu/mu). Based on the results of coagulation assays in all the female relatives investigated, nu/mu was estimated to be 12.1 by the maximum likelihood method (95% confidence interval 3.8 to 62.5). In order to avoid the possible influence of germline mosaicism, an additional analysis was performed in which only the results in the mothers and grandmothers of an isolated patient were included. The nu/mu ratio was then estimated to be 5.2 (95% confidence interval 1.8 to 15.1). Because an estimate of nu/mu based on all available RFLP data can easily be biased in favour of males, we set up a model in which only information on the grandparental derivation of the patient's X chromosome was used, irrespective of the generation in which the mutation actually occurred. In this way nu/mu was estimated to be minimally 4. The probability of carriership for mothers of an isolated haemophilia A patient amounts to 86% with a sex ratio of 5.2. Although this would imply that 14% of the mothers are not carriers of the disease in the classical sense, they may be mosaic for the mutation and, therefore, also at risk of transmitting the mutation more than once.
    Journal of Medical Genetics 11/1991; 28(10):672-80. · 5.70 Impact Factor
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    ABSTRACT: Adequate replacement therapy in haemophilia has been available for two decades. This has led to considerable improvements in the life expectancy and physical status of haemophilia patients. A study was conducted to investigate whether this has also led to improvements in quality of life. With this aim, information was obtained from 935 Dutch haemophiliacs by mailed questionnaires on relationships, marriage, family life and employment. Haemophilia patients were less often married than men in the general population (13% fewer) and had a lower total number of children (30% lower, 17% for those who were married). Twenty-two per cent of the patients were not employed and received an income from the disability funds. While severity of haemophilia, joint damage and age increased the risk of disability, it was noted that home treatment was associated with a 50% reduction in this risk. Remarkably, haemophilia patients did not differ from the general population in their view of the quality of their own health. The results of this study show a positive influence of modern haemophilia treatment on quality of life. At present, AIDS overshadows all optimistic feelings one may have about this field. However, the results described here demonstrate the benefits that can be achieved with adequate replacement therapy, and justify the expectation of further improvements in the near future.
    Journal of Internal Medicine 01/1991; 228(6):633-40. · 6.46 Impact Factor
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    ABSTRACT: A hereditary disease with excess mortality such as haemophilia is maintained in the population by the occurrence of new cases, i.e. mutations. In haemophilia, mutations may arise in female or male ancestors of a 'new' patient. The ratio of the mutation frequencies in males over females determines the prior risk of carriership of the mother of an isolated patient. An estimate of this prior risk is required for the application of Bayes' theorem to probability calculations in carriership testing. We have developed a method to estimate the sex ratio of the mutation frequencies; it does not depend on the assumption of genetic equilibrium, nor require an estimate of the reproductive fitness of haemophilia patients and carriers. Information from 462 patients with severe or moderately severe haemophilia A was gathered by postal questionnaires in a survey that included practically all Dutch haemophiliacs. Pedigree analysis was performed for the 189 patients of these 462, who were the first haemophiliacs in their family. By the maximum likelihood method, the ratio of the mutation frequencies in males and females was estimated at 2.1, with a 95% confidence interval of 0.7-6.7. In addition, we performed a meta-analysis of all published studies on the sex ratio of the mutation frequencies. When the results of six studies were pooled, it was estimated that mutations originated 3.1 times as often in males as in females. The 95% confidence interval was 1.9-4.9. This implies that 80% of mothers of an isolated patient are expected to be haemophilia carriers.
    Human Genetics 01/1991; 86(2):139-46. · 4.63 Impact Factor
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    ABSTRACT: Experiences with and attitudes toward carrier testing and prenatal diagnosis were evaluated among 549 potential and obligate carriers of hemophilia. Almost everybody considered carrier testing to be useful. Forty-nine percent had been tested for carriership, 10% had only received limited information, and 41% had not been tested and had never received information about the heredity of hemophilia. More married women, women with severe hemophilia in their family, and women closely related to a patient with hemophilia had been tested for carriership than others. Lack of information about the probability of carriership for female relatives and a similar ignorance of the possibility of carrier testing were important reasons for not having been tested. Eleven percent of the women with one or more children had undergone prenatal diagnosis in the past. Thirty-one percent of the study population would favour prenatal diagnosis with the implication of a potential abortion in early pregnancy and half of them would choose this option even in late pregnancy. Most of the women who objected to prenatal diagnosis did so because they did not consider hemophilia to be a sufficiently serious disorder to justify an abortion.
    American Journal of Medical Genetics 10/1990; 37(1):147-54.
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    ABSTRACT: We found a partial deletion of the clotting factor VIII gene of about 2000 bp, spanning exon 5 and part of intervening sequence 4 and 5 in an isolated patient with severe haemophilia A. The mother of the patient, who appeared to be a non-carrier on the basis of coagulation assays and restriction fragment length polymorphism analysis in the family, turned out to be a mosaic for the deletion, not only in her germ cells, but also in various somatic cells. These findings suggest that the mutation is the result of an event in early embryogenesis. If mosaicism for a mutation, either gonadal or somatic, proves to be a common phenomenon in human genetics, it is imperative to reconsider genetic risks for (future) sibs of any apparently new mutant of a hereditary disease.
    Human Genetics 09/1990; 85(3):288-92. · 4.63 Impact Factor
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    ABSTRACT: The influence of modern substitution therapy on social functioning of haemophiliacs was studied by means of surveys of education and employment in 1972, 1978 and 1985. In addition we studied the physical mobility of the patients. Non-attendance at school and educational delay decreased substantially over thirteen years and the educational level of adult patients is the same as that of the general male population. Sick leave decreased also but the number of disabled did not. Considering the general rise in the number of disabled, the general unemployment situation may be partly blamed for this. Younger patients have a better physical mobility than the older ones who did not have appropriate treatment of bleedings when they were young. Trends in reduction of joint impairment and increase of physical mobility are expected to continue in the coming decades, with a positive effect on social functioning.
    Nederlands tijdschrift voor geneeskunde 03/1989; 133(8):404-8.
  • [show abstract] [hide abstract]
    ABSTRACT: Mortality figures were calculated for a group of 717 Dutch haemophiliacs over the period 1973-86. Follow-up was on average 10.9 years; no patients were lost to follow-up. The data were compared to the general male population by actuarial methods and patient-year analysis. Forty-three patients died, while 20 deaths were expected in a hypothetical group of non-haemophiliacs of the same age distribution. Hence, overall mortality was 2.1 times higher than in the general population. This leads to a calculated life expectancy of 66 years, as compared to 74 years in the general male population. Mortality did not differ much by severity of haemophilia. A possibly beneficial effect of prophylaxis on longevity was observed. Haemorrhage occurred in half of all deaths and among these traumatic bleeding was the most prevalent. The number of deaths due to ischaemic heart disease was significantly lower (80% reduction) than expected and therefore the authors conclude that haemophilia offers protection against ischaemic heart disease. Cancer mortality was significantly higher (2.5 times) than expected.
    British Journal of Haematology 02/1989; 71(1):71-6. · 4.94 Impact Factor
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    ABSTRACT: A study was performed to determine whether improvements in the treatment of haemophilia over the past 20 years have influenced the prospects of these patients in the labour market. Surveys on the medical and social situation of haemophiliacs in The Netherlands were carried out in 1972, 1978 and 1985. Most of the patients participated in these surveys. Trends in employment do not show either an increase in the number of employed haemophiliacs or a decrease in the number administratively defined as disabled. However, considering the influence of the economic recession on the position of the chronically sick on the labour market and the rise in the number administratively defined as disabled in the Dutch population, haemophiliacs perform well. Sick leave has decreased considerably. Although the employment rate for the group of haemophiliacs is lower than that for the general male population, the level of employment in relation to educational achievements is high and most of the employed do not feel limited in their daily job activities by the haemophilia. Physical mobility is a main factor influencing the employment status but other factors, such as the type of occupation or former occupation and prejudice against people with haemophilia, have to be considered.
    Social Science [?] Medicine 02/1989; 28(3):261-70. · 2.73 Impact Factor
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    ABSTRACT: A study was carried out among haemophiliacs in The Netherlands to evaluate the effect of modern substitution treatment (replacing the missing clotting factors) on medical and social performance. Three questionnaires were sent between 1972 and 1985. The use of prophylactic treatment in the group of patients with severe and moderately severe haemophilia increased from 21% (n = 242) in 1972 to 36% (n = 559) in 1985. Home treatment programmes increased from 4% to 53%. Overall mortality was 2.1 times higher than in the general male population, which leads to a calculated life expectancy of 66 years compared with 74 years in the general male population. Severe joint impairment was prominent in the older age groups, reflecting insufficient treatment in the past. A sharp decrease in the use of inpatient and outpatient hospital facilities was observed as well as much less absence from school and work. It is concluded that the high costs of modern substitution treatment are fully justified.
    BMJ Clinical Research 02/1989; 298(6668):235-8. · 14.09 Impact Factor
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    ABSTRACT: We evaluated the feasibility, reliability, and acceptability of prenatal diagnosis of haemophilia A by DNA analysis of chorionic villi. Twenty-two women at risk to transmit the abnormal gene were referred for prenatal diagnosis, two of them twice. Two of the 22 women appeared to be non-carriers by DNA analysis. In one of these women, the results were known only after chorionic villus sampling had been carried out. Thirteen of the twenty carriers were heterozygous for an intragenic (Bc1I or XbaI) marker; six women were only heterozygous for the extragenic DXS52 (St14) locus. One of the women was homozygous for all the presently known DNA markers within or closely linked with the factor VIII locus. Twelve of the 22 fetuses at risk were male, ten were female. Seven of the 12 male fetuses were shown to be affected and were subsequently aborted. Four male fetuses appeared to be not affected. In one case, the diagnosis was made by use of an extragenic marker. The woman rejected fetal blood sampling to confirm the diagnosis. After birth, a normal factor VIII level was found in three of the four cases. The fourth pregnancy is still continuing. In one of the 12 male fetuses, no diagnosis at the gene level was possible. DNA analysis is expected to provide maximum certainty as to the phenotype of the fetus for approximately 60 per cent of the women; for another 37 per cent a rate of misdiagnosis of 4-5 per cent applies. In only 3 per cent of the cases will no diagnosis at the gene level be possible as yet. The new possibility of a prenatal diagnosis in the first trimester of pregnancy enabled some of these women to have a family of their own and was appreciated in particular by the women who underwent fetoscopy in an earlier pregnancy.
    Prenatal Diagnosis 08/1988; 8(6):411-21. · 2.68 Impact Factor
  • J C Dreesen, A H Bröcker-Vriends, E Bakker
    Thrombosis and Haemostasis 03/1988; 59(1):122. · 6.09 Impact Factor
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    ABSTRACT: More than 75% of all Dutch haemophiliacs participated in a mail survey that included a section on acquired immunodeficiency syndrome (AIDS). Although no cases of haemophilia-related AIDS had been reported in the Netherlands at the time of our survey, the threat of AIDS had caused considerable anxiety among Dutch haemophiliacs. This had led almost a third of the patients to change their therapy schedules. These changes were mostly not beneficial and possibly counterproductive, since they were not likely to reduce the risk of human immunodeficiency virus (HIV) infection. Measures that were advised to prevent HIV transmission, such as the use of condoms, were seldom carried out, even by the 17% seropositive individuals. We conclude that an increase in the informational efforts towards the patients is called for to avoid ill-advised treatment changes and to enhance preventive behaviour.
    Haemostasis 02/1988; 18(2):73-82.
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    ABSTRACT: We performed DNA analysis in 20 families with haemophilia A in order to evaluate its usefulness for carrier detection and prenatal diagnosis. The polymorphic BclI site within intron 18 of the factor VIII gene and the extragenic TaqI and BglII polymorphic sites which are detected by the random DNA probes designated St14 and DX13, respectively, were investigated for. Two events of recombination were found between the St14 and the haemophilia A locus in 51 informative meioses. In one of these recombinant meioses crossing over had also occurred between the DX13 and the haemophilia A locus. No further crossovers between the DX13 and the haemophilia A locus were found in 20 informative meioses. Segregation analysis of the polymorphic markers and the deleterious mutation within the families allowed a diagnosis at the gene level for 52 out of 57 potential carriers. The new method considerably decreased the uncertainty about carriership for seventeen of the nineteen women with a probability of carriership between 5% and 95% based on pedigree analysis and factor VIII assays. In seven cases chromosome and DNA analysis of a chorionic villus biopsy was carried out. Three of the fetuses were female, four were male. Three of the male fetuses had inherited the normal maternal X-chromosome and were, therefore, not affected. For another male fetus no diagnosis at the gene level was possible since the mother was homozygous for all the known restriction fragment length polymorphisms within or closely linked with the haemophilia A locus.
    Thrombosis and Haemostasis 05/1987; 57(2):131-6. · 6.09 Impact Factor
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    ABSTRACT: Two patients with partial monosomy of the short arm of chromosome 8 are described. Their clinical features were very similar. Comparison with previously reported patients confirms the existence of an 8p- syndrome. The importance of cytogenetic investigations in all infants with major congenital heart defect and facial dysmorphism or microcephaly or both is stressed.
    Journal of Medical Genetics 05/1986; 23(2):153-4. · 5.70 Impact Factor
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    ABSTRACT: We analysed DNA from individuals of five families with haemophilia B, including nineteen potential carriers. A gene-specific probe was used to reveal a TaqI restriction-fragment length polymorphism. Segregation analysis of the polymorphic marker and the deleterious mutation within families allowed diagnosis at the gene level for 16 out of the 19 potential carriers, two proving to be carriers and 14 non-carriers. The obvious advantage is that lyonisation, which is a limiting factor when gene product (clotting factor IX) measurements are used for carrier detection, does not interfere with this procedure and that the result is a definitive diagnosis instead of a risk estimate. The method also permits prenatal diagnosis on chorionic villi in the first trimester of pregnancy. Restriction-fragment length analysis, based upon the probe and restriction enzyme used in this study, will be informative for approximately 45% of the individuals at risk of carrying or transmitting the haemophilia B mutation.
    Thrombosis and Haemostasis 09/1985; 54(2):506-9. · 6.09 Impact Factor
  • Nederlands tijdschrift voor geneeskunde 07/1985; 129(24):1141-5.

Publication Stats

395 Citations
870 Views
84.35 Total Impact Points

Institutions

  • 1993
    • University of Amsterdam
      • Department of Medical Psychology
      Amsterdam, North Holland, Netherlands
  • 1988–1991
    • Leiden University Medical Centre
      • • Department of Clinical Epidemiology
      • • Department of Clinical Genetics
      Leiden, South Holland, Netherlands
  • 1990
    • University of Groningen
      • Department of Health Sciences
      Groningen, Province of Groningen, Netherlands