Recombinant porcine factor VIII corrects thrombin generation in vitro in plasma from patients with congenital hemophilia A and inhibitors. Issue 4 (19th June 2022)

• Record Type: Journal Article
• Authors: Négrier, Claude; Oldenburg, Johannes; Kenet, Gili; Meeks, Shannon L.; Bordet, Jean‐Claude; Müller, Jens; Le Quellec, Sandra; Turecek, Peter L.; Tripkovic, Nikola; Dargaud, Yesim
• Is Part Of: Research and practice in thrombosis and haemostasis. Volume 6:Issue 4(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-06-19
• Subjects: factor VIII inhibitor -- hemophilia A -- porcine factor VIII -- recombinant -- thrombin; Thrombosis -- Periodicals; Hemostasis -- Periodicals; 616.135005
• DOI: 10.1002/rth2.12731
• Languages: English
• ISSNs: 2475-0379

Abstract

Abstract: Background: Neutralizing factor VIII (FVIII) antibodies are a major complication in hemophilia A. Antihemophilic factor VIII (recombinant), porcine sequence (rpFVIII; susoctocog alfa; Baxalta US Inc., a Takeda company) has low cross‐reactivity to anti‐human FVIII antibodies and can provide functional FVIII activity in the presence of FVIII inhibitors. Objectives: Evaluate in vitro thrombin generation and clot formation responses to rpFVIII in blood from patients with congenital hemophilia A. Methods: In this multicenter study, blood was obtained for in vitro analyses that included human and porcine FVIII inhibitors, low <5 Bethesda units (BU)/ml or high ≥5 BU/ml titer (Nijmegen‐modified Bethesda assay); thrombin generation assay (TGA), clot viscoelasticity (thromboelastography), fibrin clot structure analysis (scanning electron microscopy), and epitope mapping. Results: Blood samples were from 20 patients with congenital hemophilia A (FVIII activity <1%, mean [range] inhibitor titers: anti‐human FVIII, 14 [1–427] BU/ml [ n = 13 high, n = 6 low, n = 1 data unavailable]); anti‐porcine FVIII, 12 (0–886) BU/ml ( n = 11 high, n = 8 low, n = 1 data unavailable). Porcine inhibitor titer and TGA response measured by endogenous thrombin potential showed an inverse correlation (2.7–10.8 U/ml rpFVIII Spearman correlation coefficient: −0.594 to −0.773; p < 0.01). Clot structures in low anti‐porcine inhibitor titer plasmas were similar to those in noninhibitor plasma. Conclusions: Recombinant porcine factor VIII demonstrated a dose‐dependent correction of thrombin generation and clot formation in vitro, dependent on the anti‐porcine FVIII inhibitor titer. Procoagulant responses to rpFVIII occurred in plasma containing FVIII inhibitors.