Co-morbidity and mortality in Swedish patients with haemophilia - A register study

Sammanfattning: Haemophilia is an X-linked inherited recessive disorder affecting males. The increased risk of hemorrhage is explained by the deficiency in either coagulation factor VIII (haemophilia A) or IX (haemophilia B). The severity of haemophilia A and B is characterized by the bleeding pattern. For severe haemophilia bleeding is often spontaneous, mainly in muscles and joints. Since the 1950s the manifestations and treatment of the disease have undergone dramatic changes with, formerly, a median survival of 10-15 years and today a survival comparable to the general population. However, development of the treatment was catastrophically affected by transmission of human immunodeficiency virus (HIV) and viral hepatitis through plasma-derived products until the 1980s. With an increased survival among the haemophilia population other age-related co-morbidities will inevitably become more prevalent. Studies of these co-morbidities are increasingly important, not least since their management may differ among patients with bleeding disorders. The present thesis focuses on incidence, mortality, first degree relatives, and co-morbidities over time, in Swedish persons with haemophilia compared to persons without haemophilia. This was performed by using Swedish national registries and local registries from the three haemophilia centers in Sweden: Malmö, Gothenburg and Stockholm. In Paper I the long-term outcome of haemophilia in terms of incidence, morbidity and mortality was studied. People with haemophilia in Sweden demonstrate higher mortality over time, independent of HIV and viral hepatitis, compared to the control cohort. In Paper II the family structure, focusing on children, siblings and marital status was studied. Having one or more children was less common for persons with haemophilia than the controls, especially for those infected with HIV. With respect to co-morbidities, a special focus was on malignancies and cardiovascular diseases. These were studied in Paper III and IV. Patients with haemophilia showed a higher incidence of malignancies than patients without haemophilia, again, regardless of infection with HIV or viral hepatitis. Hypertension was shown to be elevated, whereas deaths due to cardiovascular diseases were lower when compared to persons without haemophilia.