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In hemophilia A and B and von Willebrand disease, coagulation factors are absent or deficient. This impairs the capacity of the blood to coagulate and increases the risk of bleeding. The diseases are hereditary. If inadequately treated, hemophilia causes painful bleeding in joints and leads to disability. Bleeds can also occur in internal organs, e.g., the brain.
Hemophilia can be treated by replacing missing coagulation factors. The availability of coagulation factors has drastically reduced morbidity, and since the 1950s survival has increased from 15 years to nearly normal life expectancy.
In the past, patients were exposed to high risk of HIV infection and Hepatitis C transmitted via blood and blood products. Since the mid 1980s, concentrated coagulation factors have been produced by methods that have practically eliminated the infection risks. Nevertheless, several questions remain concerning optimum treatment, e.g., selecting the most appropriate dose and dosing strategy. Another question concerns the treatment of bleeding episodes (bleeds) in patients that have developed antibodies (inhibitors) that counteract the effects of factor concentrates.
- Concentrates of coagulation factors VIII and IX have good hemostatic effects on acute bleeding and during surgical intervention in patients with hemophilia A and B. As scientific evidence is limited, firm conclusions cannot be drawn about possible differences in the effects of different dosing strategies for acute bleeding and surgery. More studies of sufficient quality are needed to investigate the short-term and longterm effects of the different dosage strategies.
- Preventive treatment (prophylaxis) initiated φφ at a young age, i.e., before articular (joint) bleeding starts to appear, can prevent future joint damage. Due to a lack of studies, firm conclusions cannot be drawn regarding the optimum time to start treatment during infancy, or the optimum dose and dose interval. Another uncertainty is whether treatment should be discontinued or modified during adulthood in some patients. Such studies are difficult since the numbers of patients are small, and many years of follow-up are required to evaluate the progression of joint damage.
- In patients that have developed high levels of antibodies (inhibitors) against factor concentrates, acute bleeding can be inhibited by administering bypass agents, but it is difficult to predict the effectiveness of such treatment in individual cases. Prophylaxis with bypass agents probably has a favourable effect. When the antibody level has decreased, immunotolerance induction treatment – which usually involves daily administration of relatively high doses of factor concentrate – can halt the production of inhibitors. This means that patients can then be given normal prophylaxis and can be treated for bleeding by using normal factor doses. Treating inhibitor development is extremely demanding and costly. The available treatment options have been insufficiently assessed due to the limited group of patients and the subsequent difficulties in conducting appropriate studies.
- Patients with the more severe types of von Willebrand disease must be treated with factor concentrates that contain von Willebrand factor, and often factor VIII. The effects on acute bleeding and during surgery are good. At times, preventive treatment is necessary. Doses, dose intervals, and indications for factor concentrate treatment in von Willebrand disease have not been sufficiently studied, particularly as regards prophylaxis.
- Treating hemophilia and von Willebrand disease is expensive. The economic consequences of various treatment strategies have been insufficiently analysed due to the lack of studies on clinical effects.
- It is essential to create a national treatment register that includes defined quality indicators. Regarding the future, there is an obvious need for systematic and centralised follow-up of patients with hemophilia A and B and von Willebrand disease within the context of a national quality register aimed at documenting the short-term and long-term treatment effects.
How to cite this report: SBU. Treatment of Hemophilia A and B and von Willebrand disease. Stockholm: Swedish Council on Health Technology Assessment (SBU); 2012. SBU report no 208E.
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