Background: Acquired hemophilia A (AHA) is a rare disorder with high morbidity and mortality that results from the development of autoantibodies against factor VIII (FVIII). To manage acute bleeding, recombinant porcine FVIII (rpFVIII) can be administered intravenously as a bolus dose of 50IU/kg to 200IU/kg depending on bleeding severity and the level of baseline cross-reacting anti-porcine FVIII inhibitors(Kruse-Jarres et al., 2017). Here we describe the efficacy of rpFVIII used as a continuous infusion (CI) and compare total product utilization to bolus infusions (BI).

Methods: Retrospective chart review was conducted on patients with AHA who met the International Society on Thrombosis and Hemostasis criteria for major bleeding and who received rpFVIII at our institution from 2015 to 2020(Kaatz, Ahmad, Spyropoulos, & Schulman, 2015). Efficacy was defined as clinical bleeding control and achievement of adequate FVIII levels. Data were collected through electronic patient records and analyzed using simple descriptive (mean ± standard deviation (SD)) and inferential statistics (T-Test, alpha=0.05). Institutional Research Ethics Board approval was obtained.

Results: During the study period, 13 patients received rpFVIII (CI n=3, BI n=10). The mean age of patients receiving CI and BI was 75.3 years (SD 2.5) and 72.0 years (SD 14.5) respectively. All patients who received rpFVIII as a CI received a bolus dose ranging between 102.6IU/kg-200.8IU/kg prior to initiation of the CI. CI rates between 3.4IU/kg/hr-11.5IU/kg/hr were administered. Two of the patients receiving rpFVIII as a CI had their infusion rates adjusted according to their clinical symptoms and FVIII levels. One patient had the rpFVIII CI stopped due to an increase in anti-rpFVIII antibodies which interfered with hemostatic efficacy. Thirty-three percent of CI patients and 60% of BI patients required a red blood cell (RBC) transfusion after starting rpFVIII. Sixty-six percent of CI patients and 20% of BI patients had worsening of bleeding after initiation of rpFVIII. Lastly, rpFVIII usage in the CI group (170.4 ± 25.9 IU/kg/day) was not significantly different compared to the BI group (120.9 ± 64.4 IU/kg/day) when accounting for the duration of admission and weight of the patients (P>0.05). No thromboembolic events occurred in either group while receiving rpFVIII.

Conclusions: Our study shows that the total amount of rpFVIII administered to patients as a CI is not significantly different to those receiving BI. The CI group required less RBC transfusions but reported more exacerbation of bleeding. Thus, the efficacy of rpFVIII given as a CI requires further evaluation in future prospective studies.

Disclosures

Sholzberg:NovoNordisk: Honoraria, Other: Scientific Advisory Board; Novartis: Honoraria, Other: Scientific Advisory Board; Takeda: Honoraria, Other: Scientific Advisory Board, Research Funding; Octapharma: Honoraria, Other: Scientific Advisory Board, Research Funding; Amgen: Honoraria, Other: Scientific Advisory Board, Research Funding.

OffLabel Disclosure:

Antihemophilic Factor (Recombinant), Porcine Sequence (OBIZUR) is a purified protein produced by recombinant DNA that is a B-domain deleted recombinant factor VIII, porcine sequence, manufactured in tissue culture in baby hamster kidney (BHK) cells. OBIZUR is indicated for the treatment of bleeding episodes in patients with Acquired Hemophilia A (AHA). OBIZUR is administered as a bolus infusion.

Author notes

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Asterisk with author names denotes non-ASH members.