Treatment of acquired hemophilia A with recombinant porcine FVIII in Germany
C. Hart1, A. Huth-Kühne2, R. Klamroth3, M. Angstwurm4, M. Stemberger4, M. Spannagl4 (1Regensburg, Germany, 2Heidelberg, Germany, 3Berlin, Germany, 4München, Germany)
Bleeding disorders, coagulation and fibrinolytic factors
Date: 17.02.2017,
Time: 17:15 - 18:15
Objective: Here we report on the clinical outcome of four patients from Germany treated for acquired hemophilia A (AHA) with recombinant porcine FVIII (rpFVIII). The patients were treated in various institutions and by different physicians.
Methods: All four cases were referred from external hospitals with a major hemorrhage. Three of four cases were initially treated with bypassing agents however with limited efficacy. Subsequent treatment with rpFVIII was initiated with 100 U/kg bodyweight and 50 U/kg bodyweight, respectively.
Results: The FVIII activity increased from 13 % - 120 % within 30 min after the first rpFVIII dose in three of four cases in which the baseline anti-rpFVIII antibody titers were below 0.6 BU. rpFVIII administration was associated with satisfactory hemostasis within 24 hours. In the fourth case no increase in FVIII activity could be measured due to a baseline anti-rpFVIII antibody titer of approximately 100 BU. Here several cycles of immunoadsorption and plasmapheresis resulted in a decrease of anti-rpFVIII antibody titer (< 20 BU). The following administration of 100 U/kg bodyweight rpFVIII elevated FVIII activity to 114 % with satisfactory hemostasis within 24 hours. Subsequent doses of rpFVIII were in a range between 25 and 100 U/kg bodyweight. FVIII activity was maintained at levels between 2 % - 136 % during subsequent rpFVIII therapy. No adverse events associated with rpFVIII, including thrombocytopenia or thromboembolism, were observed. Two patients survived with successful inhibitor eradication, one patient died from E-coli sepsis with an inhibitor present and one patient was discharged and died 3 months later from acute liver and kidney failure unrelated to AHA (human inhibitor titer was negative).
Conclusion: rpFVIII administration resulted in rapid bleeding cessation. Insufficient FVIII increase after initial rpFVIII dosage due to baseline cross reactivity in one patient could be altered by immunoadsorption and plasmapheresis. Loading doses and median subsequent doses of rpFVIII were lower than those stated in the SPC. Treatment decisions were based on FVIII activity levels as well as clinical response. The considerable variability in treatment requirements and responses among these cases describe the need of treatment by experts from Hemophilia Treatment centers.