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Factor VIII products

Prophylaxis, pharmacokinetics, dosing and administration of factor VIII products

Increased awareness of disease, predictions of bleeding phenotype and improved possibilities to determine individual pharmacokinetics have opened up new possibilities in prophylaxis, as discussed below

Erik Berntorp Lund University, Malmö Centre for Thrombosis and Haemostasis, Skåne University Hospital Malmö, Sweden

Prophylactic treatment of haemophilia, or rather continuous replacement therapy of the missing coagulation factor, notably factor (F) VIII or FIX, has become the state-of-the-art treatment in the more severe forms of haemophilia. The goal of prophylaxis is to reduce, or preferably entirely prevent, bleedings into joints and also to prevent tissue and visceral bleeds and brain haemorrhages. The definition of long- term prophylaxis can be devided into primary and secondary prophylaxis (Table 1). If prophylaxis is given for less than 45 weeks per year, it is named temporary or short term. By primary

Table 1: Definition of prophylaxis1

• Primary prophylaxis determined by age Long-term continuous treatment started before the age of two years and prior to any clinically evident joint bleeding

• Primary prophylaxis determined by first bleed Long-term continuous treatment started prior to the onset of joint damage (presumptively defined as having had no more than one joint bleed) irrespective of age

• Secondary prophylaxis

Long-term continuous treatment not fulfilling the criteria for primary prophylaxis

prophylaxis is meant starting preventive replacement therapy before joint disease has started. The problem is that it is impossible to define when joint disease in haemophilia is initiated and starts to progress. In the current definitions of primary prophylaxis, replacement should be started before joint disease occurs, that is, prior to the first joint bleed or, alternatively, after the first joint bleed.1 Some authors indicate that joint disease may start after very few bleeds2 after so-called subclinical bleeds.3

or even While researchers agree that prophylaxis should

be started early, there is less consensus about dosing and about when or if to stop prophylaxis. Prophylaxis has a long tradition in countries like Sweden and The Netherlands4,5

but was not generally

accepted until studies with rigorous scientific evidence proved its advantage compared to treatment on demand.3,6

to the high cost of treatment, dose schedules have not yet been fully delineated. In later years, individual tailoring of prophylaxis using pharmacokinetics has indicated possibilities to lower the cost. Due


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