Issues surrounding therapeutic choices for hemophilia patients.

Of the several clinical issues surrounding therapeutic choices for hemophilia patients, prophylactic therapy stands out as the most positive. The first study comparing prophylactic and on-demand treatment , which involved 22 years of follow-up, found that the primarily prophylactic treatment strategy led to better outcome at equal treatment costs in young adults with severe hemophilia. 1 In contrast, one of the most challenging issues in hemophilia treatment is development of inhibitors to factor VIII (FVIII). Previous reports of inhibitor development risk have varied widely, ranging from approximately <5% to 40%. 2-5 This variability may stem from patient-related, therapy-related, and assay-related influences on inhibitor development and detection, as reported by Wight and Paisley in a current review. 2 Their systematic review concluded that, based on large-scale prevalence studies and hemophilia registry data, 5% to 7% of all hemophilia patients have antibodies to FVIII, with a substantially higher prevalence of approximately 13% among those with severe disease (with prevalence referring to the proportion of the patient population with inhibitors at a given time). 2 On the other hand, the cumulative risk of inhibitor development (number of new cases over a prolonged period adjusted for different patient follow up durations) varied from 0% 6 to 39%. 7 In any case, inhibitor development complicates patient management and may require immune tolerance induction. Other important issues attendant on FVIII therapy , whether preventive or acute, include cost, venous access, FVIII dosage and dosing intervals, and joint scoring systems. The rationale for prophylactic treatment of hemo-philia is based on observations that patients with moderate hemophilia (FVIII/FIX >0.01-0.05 IU/mL) rarely develop chronic arthropathy. 8 Moreover, many studies have shown that, even at high doses, on-demand therapy is not effective in preventing arthropathy. The possibility of changing the clinical phenotype of patients with severe hemophilia to a moderate phenotype has been a challenge. Without adequate therapy , patients with severe hemophilia (FVIII/FIX < 0.01 IU/mL) have a life expectancy of about 20 years, during which they suffer from severe bleeds, spontaneous or from minor trauma, and early, crippling arthropa-thy. 11 Those with moderate disease experience only traumatic bleeds and, in turn, develop far less arthropathy. It follows, therefore, that increasing the level of clotting factor activity to at least 1% with prophylactic therapy should prevent bleeding in patients with severe hemophilia. As defined by the European Paediatric Network for Haemophilia Management, primary prophylaxis is started before the age …