Abstract
The development of neutralizing FVIII-antibodies is one of the most serious complication in the replacement therapy with FVIII and IX concentrates in hemophilia A and B patients. In order to observe different parameters with possible impact on inhibitor development in PUPs with hemophilia A and B a prospective study was started in 1993 by the GTH (German, Swiss and Austrian Society on Thrombosis and Haemostasis Research).
The study protocol provides frequent inhibitor testing particularly during the initial 200 exposure days (ED) according to the modified Bethesda method (central lab Prof. Budde, Hamburg) and correlates inhibitor development with age at first exposure, therapy regimen, dosage, mutation type, type of concentrate and further variables which may have an impact on inhibitor development. Until September 2003, 293 patients with hemophilia A and B have been enrolled in this ongoing study. 206 have been treated (176 hemophilia A, 30 hemophilia B) at least once with plasma derived (pd) or recombinant (r) factor (F) VIII or IX concentrates.
Out of 176 hemophilia A patients 35 developed inhibitors (16 high titer >5 Bethesda Units/BU, 17 low titer >0.6–5 BU, 2 transient low titer inhibitors) after 12 exposure days (ED) in median (range 1–56) at the age of 0.9 years (median, range 0.25–10.8). Inhibitor development was predominantly observed in severe hemophilia A patients (31%) and to a lesser extent in moderate patients (7.7%). Inhibitor incidence was higher in patients receiving recombinant FVIII products than in those treated with plasma derived concentrates (p=0,14). No correlation between age at first exposure and inhibitor development was found. Early prophylaxis resulted in a lower inhibitor incidence than on-demand treatment (p=0.003).
Out of 16 severely affected hemophilia B patients 2 developed inhibitors.
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