Inhibitor development in two patients with mild haemophilia A – spontaneous disappearance and no recurrence of the inhibitor after re-challenge

Abstract

Inhibitors against factor VIII (FVIII) complicate the treatment of patients with haemophilia. In mild haemophilia, the development of antibodies against FVIII is rare. However, the occurrence of an inhibitor in mild haemophilia changes the bleeding phenotype from mild to severe, and thus becomes a major clinical problem. We report on two patients with mild haemophilia A (FVIII level 8 and 27%, respectively), who have a missense mutation in exon 16 (G to A transition in codon 1773) and exon 22 (T to C transition in codon 2096), respectively. Both mutations have not been described in the Haemophilia A Mutation, Structure Test and Resource Site. Our patients developed high titer inhibitors following an intensive FVIII replacement therapy due to a muscle bleeding and after a polytrauma. During the presence of the inhibitor, AICC or FVIIa was successfully used as bypassing agent. In both patients the inhibitor disappeared spontaneously. Years after the development of the inhibitor, the patients again received FVIII concentrates. Reappearance of the inhibitor was not observed in either patient. The reported cases indicate that inhibitors in patients with mild haemophilia might be transient and disappear spontaneously. Therefore, the necessity of immune tolerance therapy, which is costly and strenuous for the patients, should be critically examined for each individual patient and a watch and wait strategy might be advisable.

Use of factor VIII after inhibitor clearance in patients with moderate haemophilia A: a case series

“…In the absence of ITI, there is little written about whether persons with non-severe haemophilia A who develop an inhibitor can restart FVIII replacement therapy after resolution of their inhibitor outside of the ITI setting without inhibitor recurrence. A recent publication reported two cases of persons with mild haemophilia A who had spontaneous resolution of their inhibitors and after rechallenge with FVIII at the time of invasive procedures (first patient for right hip surgery and second patient for liver biopsy) had no recurrence of inhibitor [8]. To our knowledge, there are no published reports of describing the re-initiation of FVIII replacement therapy outside of ITI in persons with moderate haemophilia A (MHA) complicated by an inhibitor.…”