Co-morbidity in adult haemophilia patients

Abstract

Haemophilia is an X-linked inherited bleeding disorder, caused by a deficiency of clotting factor VIII or IX. Due to the availability of treatment with clotting factor concentrates, life expectancy of haemophilia patients is now approaching that of the general population. Haemophilia patients are therefore increasingly confronted with age-related types of co-morbidity, such as cardiovascular disease (CVD) and malignancies. In two retrospective evaluations we performed in large cohorts of haemophilia patients, however, the cumulative incidence of acute ischemic cardiovascular events appeared to be lower in patients with severe haemophilia than in the general age-matched male population, while the occurrence of angina pectoris was similar. This suggests that (very) low clotting factor levels might have a protective effect against acute thrombotic arterial occlusion, but not against atherosclerosis development. Baseline data of a prospective study on CVD occurrence and risk factors in over 700 haemophilia patients showed that the prevalence of hypertension was significantly increased in haemophilia patients compared with the general population. Moreover, haemophilia patients had more unfavourable overall CVD risk profiles. The prospective follow-up of these patients will have to determine whether the occurrence of cardiovascular events is indeed lower than in the general population, despite the more unfavourable risk profiles. In our retrospective analyses, the occurrence of malignancies (other than hepatocellular carcinoma) was similar in haemophilia patients and the general population. Unfortunately, in the past, many patients with inherited bleeding disorders were infected with hepatitis C (HCV) and/or HIV due to the use of contaminated clotting factor concentrates. HCV can be ‘silently’ present in the liver for several decades, but can eventually lead to liver fibrosis, liver cirrhosis and hepatocellular carcinoma. The aim of antiviral treatment is to eradicate HCV and stop progression of liver damage. In a large cohort of HCV infected patients with inherited bleeding disorders with over 30 years of follow-up, we found that a significant proportion of patients had developed end-stage liver disease (ESLD) and that hepatocellular carcinoma appeared to be an increasing problem. After successful antiviral treatment, however, hardly any cases of ESLD occurred. Antiviral treatment must be administered for 24-48 weeks and has many side-effects, of which depression seems to be underestimated. Fortunately, these side-effects are mostly transient. Liver stiffness measurements (LSM) using Fibroscan® is a relatively new, non-invasive method to determine the extent of liver damage and help guide treatment decisions and determine prognosis. When used longitudinally, LSM appears to behave similarly to serial liver biopsies in patients with chronic HCV infection, but interpretation of the results can be difficult in individual patients. In patients who underwent successful antiviral treatment, LSM showed that this treatment has a large and lasting beneficial effect on the extent of liver damage. The impact of HIV infection has decreased significantly after the introduction of highly-activated antiretroviral treatment (HAART) in the 1990s. Before this time, many HIV infected haemophilia patients died of AIDS. HAART can, however, have serious side-effects, such as diabetes mellitus and possibly an increased risk of spontaneous intracranial bleeding.