Safety surveillance in haemophilia and allied disorders

Abstract

The introduction of clotting factor concentrates has transformed the lives of persons with inherited bleeding disorders. With the use of prophylactic treatment, it is now possible to prevent bleeding in these individuals. The early concentrates were contaminated with the HIV and hepatitis C viruses (HCV) and resulted in major morbidity and mortality in the recipients. Current products are much safer, especially in terms of infectious agents, but other adverse events such as alloantibodies (inhibitors), allergic reactions and thrombotic risks remain of concern. Approximately 30% of previously untreated patients with severe haemophilia A develop inhibitors, making this the most important issue in haemophilia care today. Recently, it was suggested that one of the most commonly used concentrates was associated with a higher inhibitor risk, but this was not supported by the evidence from all studies. Good safety surveillance systems are essential for all diseases and products but are particularly so in the group of individuals with inherited bleeding disorders treated with clotting factor concentrates who have suffered disproportionately from the adverse effects of their treatment. National and multinational systems are now in place to allow reporting of adverse events in patients with inherited bleeding disorders. All clinicians treating individuals with inherited bleeding disorders should prospectively report adverse events to treatment even if they are believed to be common and well recognized.

The current state of adverse event reporting in hemophilia

“…On the other hand, concern remains for the possible transmission by plasma-derived products of parvovirus B19, Creutzfeldt-Jakob disease, hepatitis E, as well as for a number of new pathogens (West Nile, Zika, Dengue) and currently unknown agents [9].…”

“…Many countries have generic schemes by which doctors, other health professionals and often patients can report adverse events for any medicinal product [9]. In the UK the scheme is known as the yellow form scheme, named after the color of the form used for submission of the adverse event information.…”

“…National schemes for reporting adverse events exist in the UK, France, Netherlands, Italy, Canada, USA and Australia [9]. These schemes vary in the detail of the information collected and the length of time they have been in existence.…”

“…Clinicians in the UK report inhibitors, thromboses, malignancies, deaths as well as all treatments with concentrate. 9 In France, the FranceCoag network collects high quality data on inhibitor development in all patients with haemophilia [20]. The reported data are checked by auditors that visit the centers to confirm the accuracy of the information.…”

“…In terms of adverse events the RODIN study collects data only on inhibitor development. [9,46,47]. Table 3 shows the type of events reported in EUHASS, and …”