Successful eradication of a FVIII inhibitor in a 60-year-old patient with mild haemophilia A using single-agent prednisolone

 

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Summary

Background Development of FVIII inhibitors represents a major challenge in patients with mild haemophilia A (HA), because they tend to occur at an older age and classical immune tolerance induction appears to be less effective. Case report A man (age: 60 years) with mild HA due to the missense mutation, Leu1929Arg, received a single dose of rFVIII at 35 IU/kg prior to routine colonoscopy, totalling 25 lifetime exposure days. Two months later, rFVIII was infused for a traumatic hip haematoma. However, FVIII recovery was inappropriate, and a FVIII inhibitor of 19 BU with type-2 kinetics was detected, resulting in FVIII:C of < 1%. Two weeks later, the patient experienced spontaneous iliopsoas bleeding. Parallel to bypassing therapy, we started single-agent immunosuppression with prednisolone at 1.5 mg/kg. FVIII : C “normalized” at 10.2% after four weeks. After five months, the inhibitor titre fell to < 0.4 BU with sustained remission after one year of follow-up. Conclusion In mild HA, FVIII inhibitors may share characteristic features with FVIII autoantibodies commonly observed in acquired HA. Therefore, immunosuppressive therapy alone could be successful at least in a subset of patients.

Zusammenfassung

Hintergrund Inhibitoren bei Patienten mit milder Hämophilie A (HA) stellen eine besondere Herausforderung dar, da sie häufig in höherem Alter auftreten, und da die klassische Immuntoleranzinduktion weniger effektiv zu sein scheint. Fallbericht Ein Mann (Alter: 60 Jahre) mit milder HA und einer Missense-Mutation (Leu1929Arg) erhielt einmalig 35 IE/kg rFVIII zur Koloskopie. FVIII:C war 9,5% und der Inhibitor 0,5 BE. Zwei Monate später wurde rFVIII bei traumatischem Hüfthämatom verabreicht. Bei inadäquater FVIII-Recovery wurde ein Inhibitor von 19 BE mit einer Typ 2-Kinetik diagnostiziert. FVIII : C fiel auf < 1%. Zwei Wochen später erlitt der Patient eine spontane Iliopsoas blutung. Parallel zu Bypasspräparaten wurde eine immunsuppressive Therapie mit Prednisolon (1,5 mg/kg Körpergewicht) begonnen. FVIII : C “normalisierte” sich auf 10,2% nach vier Wochen. Nach fünf Monaten war der Inhibitor auf <0,4 BE gefallen. Nach insgesamt einem Jahr war der Patient noch in kompletter Remission. Schlussfolgerung Inhibitoren bei milder HA zeigen mitunter typische Eigenschaften von Autoantikörpern bei erworbener Hämophilie. Deshalb erscheint die alleinige Immun suppression zumindest bei einigen Patienten Erfolg versprechend.

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