Factors predictive of death among HIV‐uninfected persons with haemophilia and other congenital coagulation disorders

Abstract

Historically, the leading cause of death among persons with haemophilia and other congenital coagulation disorders was uncontrolled bleeding. Mortality was associated with severe deficiency of coagulation factors VIII or IX and especially with high-titre antifactor neutralizing antibodies (inhibitors). The catastrophic contamination of plasma donor pools with human immunodeficiency virus (HIV) resulted in acquired immunodeficiency syndrome replacing haemorrhage as the leading cause of death among persons with haemophilia. Rather little has been written, however, about mortality among those not infected with HIV. The objective of this study was to identify conditions associated with all-cause mortality among HIV-uninfected patients who were followed for a mean of 8.8 years in the Multicentre Hemophilia Cohort Study. Among the 364 children (mean age 8 years), there were four deaths; two related to cancer, one to trauma, and the fourth to haemorrhage, end-stage liver disease and sepsis. Among the 387 HIV-uninfected adults (mean age 35 years) there were 29 deaths, with haemorrhage the leading cause of death, followed by hepatic, stroke and cancer deaths. Prognostic factors for all-cause mortality among the adults included haemophilia Type A with neutralizing antibodies [age-adjusted relative rate (RR) 3.1, 95% confidence interval (CI) 1.4-6.9] and serologic evidence of both hepatitis B and C virus (RR 4.1, 95% CI 0.97-17.6). Although hepatitis C viral load was slightly lower in patients with hepatitis B virus surface antigenaemia, it was unrelated to vital status. We conclude that causes of death and prognostic factors for current HIV-uninfected haemophilia patients are similar to those noted before the HIV epidemic. Better understanding, prevention and control of neutralizing antibodies and hepatitis infections may substantially improve longevity for people with haemophilia.

Mortality rates, life expectancy, and causes of death in people with hemophilia A or B in the United Kingdom who were not infected with HIV

“…16 A study of the causes of death in people with hemophilia in Sweden during 1957 to 1980 reported that intracranial hemorrhage accounted for 38% (15/39) of all deaths in people with severe hemophilia, 17 and the proportion of deaths involving intracranial hemorrhage was only slightly lower than this in the present study, at 34% (84/250). Intracranial hemorrhage was also found to be the leading cause of death in studies covering this time period of people with hemophilia at all ages in the Netherlands, 11 the United States, 18,19 and France. 20 The French study 20 reported 3 deaths from intracranial hemorrhage in neonates during the 1990s.…”

Mortality and causes of death in Italian persons with haemophilia, 1990–2007

“…The value of this analysis mainly relies in providing novel data on mortality in the Italian population of PWH that adds up to those already available from countries like UK, Canada, US, Spain, the Netherlands. These results can be compared with studies that did evaluate mortality and causes of death in the whole population of PWH [11–15], as well as and with those that analysed specific subpopulations, namely HCV‐ or HIV‐infected PWH. Results cover the whole history of the therapeutic approach to PWH, spanning from the dramatic increase in life expectancy between the 1960s and 1980s as a result of the widespread availability of replacement therapy with plasma‐derived concentrates to the catastrophic contamination of these concentrates by HIV and HCV in the 1980s.…”

“…There are several reports on mortality in PWH [6–15]. However, while half of them focussed on mortality in specific subpopulations of patients such as those infected with HIV and HCV and yet others excluded PWH with blood‐borne infections [6–10], only very few studies analysed mortality and causes of death in the whole haemophilic population, especially after the end of the era of the highest risk of blood‐borne virus transmission [11–15]. With the aim of comparing the periods before and after the use of infectious coagulation factors, and also considering that none of the available studies was conducted in Italy, we chose to review mortality rates and causes of death among Italian PWH during the study period 1980–2007, and to analyse the factors which contributed to the variation of the mortality rate and related improvement in life expectancy.…”

Coronary artery calcification score and carotid intima–media thickness in patients with hemophilia

“…Furthermore, in patients with hemophilia and cardiovascular disease, the presence of coronary disease and cardiovascular morbidity and mortality were associated with the same traditional risk factors as in the general population. Cardiovascular disease in patients with hemophilia has attracted more interest in recent years, because decreased mortality from bleedings and viral infections has resulted in a longer life‐expectancy and consequently longer exposure to cardiovascular risk factors [7–9].…”