Abstract Number: PB0775
Meeting: ISTH 2020 Congress
Theme: Hemophilia and Rare Bleeding Disorders » Acquired Hemorrhagic Coagulation Disorders
Background: Development of anti-FVIII inhibitors is a major complication of the treatment of patients with hemophilia A. Antihemophilic factor VIII (recombinant), porcine sequence (rpFVIII; susoctocog alfa, OBI-1, BAX 801, TAK-672; Baxalta US Inc., a Takeda company, Lexington, USA) has low cross-reactivity to anti-human FVIII antibodies, and can result in therapeutic levels of functional FVIII activity despite the presence of antibodies.
Aims: To evaluate the hemostatic efficacy of rpFVIII in vitro using blood samples from patients with acquired hemophilia A and FVIII inhibitors, and commercially available FVIII-depleted plasma spiked with monoclonal antibodies to FVIII as determined by thrombin generation assay and thromboelastography.
Methods: Blood samples collected from patients attending routine hemophilia center visits (ethical approval and patient informed consent obtained) were assessed for FVIII inhibitors using the Nijmegen-modified Bethesda assay. Thrombin generation time course was determined at low tissue factor (1pM) concentration. Variables measured were lag time, peak height, and endogenous thrombin potential (ETP). Samples were classified by Bethesda titer as low (< 5 BU/mL) or high (≥5 BU/mL) for both human and porcine inhibitors, and stratified into subgroups: 1) low anti-human/low anti-porcine; 2) high anti-human/low anti-porcine; 3) high anti-human/high anti-porcine.
Results: Data from 19 patients were analyzed. Mean (range) anti-human FVIII inhibitor titer was 14 (1-427) BU/mL (14 high, 6 low), anti-porcine FVIII inhibitor titer was 12 (0-886) BU/mL (11 high, 9 low). A modest-to-moderate inverse correlation was found between anti-porcine inhibitor titer and thrombin generation response using ETP by addition of rpFVIII for concentrations of 2.7-5.4 U/mL (r: -0.520 to -0.573; P< 0.03; Table 1). Anti-human inhibitor titer did not affect thrombin generation (0.87; P=0.00006).
Conclusions: rpFVIII correction of thrombin generation appears to be dependent on the anti-porcine inhibitory antibody titer and not on the anti-human inhibitory titer. Consistent with real-world observations, presence of pre-existing FVIII inhibitors does not exclude a positive response to rpFVIII.
| rpFVIII concentration (U/mL) | n | Correlation: anti-porcine inhibitor and ETP* | P value | Correlation: anti-porcine inhibitor titer and peak height* | P value |
| 0 | 19 | -0.003 | 0.9903 | -0.084 | 0.7412 |
| 2.7 | 19 | -0.520 | 0.0270 | -0.644 | 0.0027 |
| 5.4 | 19 | -0.573 | 0.0130 | -0.717 | 0.0008 |
| 10.8 | 19 | -0.426 | 0.0781 | -0.590 | 0.0099 |
| ETP, endogenous thrombin potential; rpFVIII, recombinant porcine factor VIII. | |||||
| *Anti-porcine inhibitor values as measured by local laboratories and ETP and peak height as measured by central laboratory. | |||||
[Table 1. Spearman rank correlation between anti-porcine titer and thrombin generation response by addition of rpFVIII]
To cite this abstract in AMA style:
Négrier C, Oldenburg J, Kenet G, Tripkovic N, Meeks SL. In vitro Correction of Thrombin Generation by Recombinant Porcine Factor VIII (rpFVIII) in Plasma Containing Anti-Factor VIII Inhibitory Antibodies [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/in-vitro-correction-of-thrombin-generation-by-recombinant-porcine-factor-viii-rpfviii-in-plasma-containing-anti-factor-viii-inhibitory-antibodies/. Accessed December 2, 2022.« Back to ISTH 2020 Congress
ISTH Congress Abstracts - https://abstracts.isth.org/abstract/in-vitro-correction-of-thrombin-generation-by-recombinant-porcine-factor-viii-rpfviii-in-plasma-containing-anti-factor-viii-inhibitory-antibodies/