Recombinant porcine FVIII for bleed treatment in acquired hemophilia A: findings from a single-center, 18-patient cohort

Abstract

Acquired hemophilia A (AHA) is a rare bleeding disorder in which acquired autoantibodies to endogenous factor VIII (FVIII) decrease FVIII activity and lead to a bleeding phenotype. A substantial majority of individuals who develop AHA present with severe bleeding. Effective treatment requires both immunosuppressive therapy and prompt hemostatic treatment. Bleeding is commonly treated with bypassing agents (BPAs) such as recombinant activated FVII (rFVIIa) or activated prothrombin complex concentrates Disadvantages to BPAs include the inability to monitor response with standard laboratory assays, inconsistent hemostatic efficacy, and thrombosis. Recombinant porcine FVIII (rpFVIII: Obizur, Baxter, Deerfield, IL) was approved by the US Food and Drug Administration (FDA) for bleed treatment in AHA in 2014, and has the advantage of laboratory monitoring of FVIII activity levels and known hemostatic efficacy in the presence of anti-human FVIII inhibitors and after failure of BPAs. Using an algorithm-based approach, rpFVIII has been used to successfully treat 18 patients with AHA at our center with substantially lower doses than the current FDA-recommended dosing. Additionally, data from our cohort show that the preexposure anti-porcine Bethesda titer does not reliably predict the clinical response to rpFVIII treatment and is not correlated with the anti-human Bethesda titer. We also present data showing lower total rpFVIII use for initial bleed resolution when rpVIII is used upfront, as compared with use as rescue therapy. We validated our dosing algorithm, which uses much lower than FDA-recommended doses with 14 more patients than in our previously reported patient series.

Emicizumab reduces re‐hospitalization for bleeding in acquired haemophilia A

“…3 Our AHA population was primarily comprised of elderly subjects with multiple comorbidities, including increased cardiovascular and thromboembolic risk factors, who generally presented with major bleeding. 6 Due to the potential thrombogenicity of simultaneous emicizumab and bypassing agent usage, our preference has been to use rpFVIII as the first-line agent for the management of bleeding at presentation. Since emicizumab negates the ability to easily track FVIII levels using the one-stage assay, and also because it does not rapidly achieve steady-state plasma levels, we delay initiation of emicizumab prophylaxis until the presenting bleed is under control, and rpFVIII is no longer required.…”

Laboratory coagulation tests and recombinant porcine factor VIII: A United Kingdom Haemophilia Centre Doctors’ Organisation guideline

“…In the cohort reported by Ellsworth et al., rpFVIII inhibitor titres post‐treatment ranged from 0 to 212 BU. The increase in cross‐reacting rpFVIII inhibitor titres were higher in individuals who lost response to rpFVIII 30 . In the Italian multicentre study, two patients developed low titre inhibitors that did not compromise treatment 31…”

“…In some patients treated with rpFVIII no increase in cross‐reacting rpFVIII inhibitors were observed following therapy 26,28,29 . The experiences of using rpFVIII in AHA was reported by the two largest cohorts to date, rpFVIII titres were measured in patients prior to initiation of rpFVIII and after exposure 30,31 . In the cohort reported by Ellsworth et al., rpFVIII inhibitor titres post‐treatment ranged from 0 to 212 BU.…”

New Developments in Diagnosis and Management of Acquired Hemophilia and Acquired von Willebrand Syndrome

“…In patients in whom rpFVIII was used upfront, an initial dose of 100 U/kg was used, followed by doses after 4–8 hours depending on the reached FVIII level. 24 It is recommended to closely monitor FVIII levels over time and to keep the levels of FVIII >50% in patients with severe bleeding. 21 In a minority of patients, the autoantibodies against human FVIII are cross-reactive to the administered recombinant porcine FVIII.…”