ArticleResearch and practice in thrombosis and haemostasis2024
Clot formation and fibrinolysis assays reveal functional differences among hemostatic agents in hemophilia A plasma.
Article in Research and practice in thrombosis and haemostasis, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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4 authors at 2 institutions in 2 countries.
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Abstract
Background: Measuring the activity of hemostatic agents used to treat hemophilia A often requires drug-specific assays. Objectives: To compare effects of established and emerging hemostatic agents on clot formation and fibrinolysis in hemophilia A plasma. Methods: Pooled and individual hemophilia A platelet-poor plasmas were spiked with replacement (recombinant factor VIII [rFVIII], PEGylated rFVIII, polysialylated rFVIII, and porcine rFVIII) or bypassing (emicizumab, rFVIIa, and activated prothrombin complex concentrate) products. Effects on tissue factor-initiated clot formation and fibrinolysis were measured by turbidity. Results: Compared to normal pooled plasma, hemophilia-pooled plasma showed reduced clot formation and increased fibrinolysis, and all replacement agents improved these characteristics. rFVIII and PEGylated rFVIII produced similar effects at similar concentrations, whereas polysialylated rFVIII produced slightly higher and porcine rFVIII slightly lower effects at these concentrations. Bypassing agents enhanced clot formation and stability, but patterns differed from replacement agents. The clotting rate showed a concentration-response relationship for all agents. High concentrations of all products produced effects that exceeded the normal range in at least some parameters. Responses of individual donors varied, but all agents improved clot formation and stability in all donors tested. Conclusion: Clotting and fibrinolysis assays reveal hemostatic effects of replacement and bypassing therapies at clinically relevant concentrations. These assays may help characterize hemostatic agents and optimize dosing.
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