Acquired haemophilia and haemostatic control with recombinant porcine factor VIII: case series

Abstract

Background Acquired haemophilia A (AHA) is a rare acquired bleeding disorder that can present with life‐threatening bleeding. Aims To describe recent Australian use of recombinant porcine factor VIII (rpFVIII) replacement therapy as a haemostatic agent in patients with acquired haemophilia. Methods Four patients with acquired haemophilia treated in three different institutions around Australia in the past 12 months were included in the study. Haemostatic efficacy of Obizur (Takeda) was assigned by the treating haematologist according to previously published criteria. Results Six bleeds were treated with rpFVIII, three of which were initially refractory to treatment with recombinant VIIa. rpFVIII was rated efficacious in 100% of bleeds by 24 h. rpFVIII loading dose was 100 U/kg (100–120 U kg−1) and this increased the factor VIII level (via one‐stage FVIII assay) from <1–1.2% to 54–306% taken 0.5–1.5 h post‐infusion. Subsequent doses ranged from 40 to 60 U/kg twice daily or daily for 3 to 13 days. No rpFVIII related adverse events occurred. Three of the four patients achieved complete remission and were weaned from immunosuppression. One patient died prior to achieving partial remission, secondary to an arterial ischaemic event. Conclusion This case series demonstrates that recombinant porcine FVIII is efficacious to treat acute bleeds in acquired haemophilia, including in those who are refractory to bypassing agents. Doses of rpFVIII were able to be titrated based on FVIII level and clinical response.

Critical Bleeding in Acquired Hemophilia A: Bypassing Agents or Recombinant Porcine Factor VIII?

“…Of note, the starting dose of 200 U/kg administered in the trial, and recommended by the manufacturer, has not been used in the real-world reports after licensure. [15][16][17][18] The lower doses of 50 to 120 U/kg used in these cases were usually effective. In the Tarantino series, 16 100 U/kg was used in six of seven patients, and resulted in FVIII peak levels >100 IU/dL in five of those.…”

“…7 rpFVIII efficacy data are available from the registration trial, comprising 29 patients, 14 and from a few case reports and series. [15][16][17][18] The trial excluded patients with a cross-reacting antiporcine inhibitor titer of >20 BU/mL. Of the qualifying bleeds reported in evaluable 28 patients, 100% showed an effective or partially effective hemostatic response after 24 hours.…”

“…In the EACH2 registry, the number of patients with thromboembolic events was 3 in 63 treated with APCC (4.8%), 5 in 174 with rFVIIa (2.9%), and 0 of 70 (0%) with human FVIII or desmopressin. 7 With rpFVIII, no thromboembolic events have been reported so far, [14][15][16][17][18] but the total number of patients (40) is too low to allow for a good estimate.…”

Recombinant porcine factor VIII: Lessons from the past and place in the management of hemophilia A with inhibitors in 2021

“…Two recent independent studies reported that cross‐reacting inhibitors were more frequent in people with anti‐hFVIII inhibitor titers >100 BU/mL 45,46 . Following drug approval, some case reports and studies on cohorts of people with acquired hemophilia A treated with r‐pFVIII have been published, all confirming susoctocog alfa good efficacy and safety for the management of severe bleeding episodes 47‐49 . A retrospective case series (n = 4 individuals with acquired hemophilia A) showed that this molecule is effective and safe.…”

“… 45 , 46 Following drug approval, some case reports and studies on cohorts of people with acquired hemophilia A treated with r‐pFVIII have been published, all confirming susoctocog alfa good efficacy and safety for the management of severe bleeding episodes. 47 , 48 , 49 A retrospective case series (n = 4 individuals with acquired hemophilia A) showed that this molecule is effective and safe. However, after a mean of 12.4 exposure days, pFVIII inhibitors were detected, resulting in a decreased efficacy and duration of the effect.…”