Treatment of Haemophilia A with Recombinant Antihaemophilic Factor VIII Products

European Haematology Review, 2007;1(1):11-15

Haemophilia A (classic haemophilia) is an X-chromosome-linked bleeding disorder occurring in approximately one in 5,000–10,000 males worldwide.1,2 Haemophilia A is caused by a partial or total deficiency of functionally active coagulation factor VIII (FVIII). Haemophilia produces abnormal bleeding that may be mild, moderate or severe depending on the degree of FVIII deficiency. Individuals with severe haemophilia A have FVIII levels <1% of normal activity (<0.01IU/ml), whereas moderate (factor level 0.01–0.05IU/ml) to mild (factor level >0.05–0.40IU/ml) forms have 1–5% and 5–40% of normal activity, respectively.1 In patients with severe haemophilia A, the first bleeding typically occurs during early childhood. The bleeding can involve any anatomical region but most commonly involves the joints (frequently elbows, knees and ankles) and muscles. Joint haemorrhages can result in severe arthropathy and degenerative damage, as found in osteoarthritis, as well as inflammatory processes similar to rheumatoid arthritis.3 In contrast to severe haemophilia A, which is characterised by spontaneous bleeding and/or severe bleeding after minor trauma, mild haemophilia A may go undiagnosed until adulthood due to the lack of spontaneous bleeding. The diagnosis of haemophilia A is confirmed by the finding of normal platelet count and function, normal bleeding time, normal prothrombin time and normal von Willebrand factor (VWF). FVIII binding activity is present, but there is prolonged activated partial thromboplastin time (aPTT) and reduced FVIII activity (FVIII:C).1,2 The diagnosis is completed by molecular genetic testing to identify the genetic defect.
Haemophilia A is incurable, but treatment with antihaemophilic therapy can stop or prevent bleeding episodes, reduce the associated morbidity, improve quality of life and normalise life expectancy. For patients with mild haemophilia A, treatment with desmopressin (DDAVP) is usually sufficient to manage bleeding episodes.2 However, for patients with mild haemophilia A who do not respond adequately to DDAVP, and for those with moderate or severe forms of the disease, replacement of the deficient factor with commercially prepared FVIII concentrates is generally required. Infusion of these concentrates temporarily increases the plasma level of FVIII and improves clinical symptoms when given on demand for bleeding episodes or during emergency situations or prophylactically to prevent spontaneous bleeding (e.g. in severe haemophilia) or for elective surgery.
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