Journal of thrombosis and haemostasis : JTH · 2025
Effect of heparins, direct oral anticoagulants, and factor XII/factor XI inhibitors on catheter-initiated thrombin generation in platelet-rich plasma: an in vitro study.
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Hardy Michael, Thonon Henri, Douxfils Jonathan, Vassart Julie, Gouin-Thibault Isabelle, Lessire Sarah, Lecompte Thomas, Mullier François
Аннотация
BACKGROUND: Invasive endovascular procedures often require anticoagulation to prevent device-associated thrombosis. High doses of unfractionated heparin (UFH) are the gold standard. The efficacy of factor (F)XII(a) and FXI(a) inhibitors remains unexplored.
OBJECTIVES: We aimed to investigate, using a validated in vitro model of catheter-initiated thrombin generation (TG) in platelet-rich plasma (PRP), the effects of garadacimab, abelacimab, asundexian, and milvexian and of commonly used anticoagulants apixaban, dabigatran, fondaparinux and heparins (enoxaparin and UFH).
METHODS: Anticoagulants were added to PRP at 6 concentrations and effects compared with UFH as a reference. The impact of adding anticoagulants into collection tubes before most preanalytical contact activation was also assessed. Concentrations achieving a 50% reduction in TG peak height (PH) were determined (IC50).
RESULTS: All anticoagulants prolonged lag time (LT) and reduced PH and endogenous thrombin potential, albeit to varying extents. UFH was the only anticoagulant able to suppress TG at clinically achieved concentrations (1 U/mL). The following IC50 were found: milvexian, 2400 ng/mL; apixaban and dabigatran, 175 ng/mL; fondaparinux, 2.4 μg/mL; enoxaparin, 0.5 U/mL; and UFH, 0.25 U/mL. Asundexian up to 5000 ng/mL failed to reduce TG PH by 50%. Adding garadacimab and abelacimab to collection tubes resulted in greater efficacy than when added to PRP: LT increased by 89% and 32%, respectively; IC50 were 25 and 12.5 μg/mL, respectively.
CONCLUSION: Heparins were by far the most effective anticoagulants in our in vitro model. FXIIa and FXI(a) inhibitors did not adequately prevent coagulation on the studied artificial surface. Direct oral anticoagulants and fondaparinux showed limited efficacy, aligning with clinical observations.
OBJECTIVES: We aimed to investigate, using a validated in vitro model of catheter-initiated thrombin generation (TG) in platelet-rich plasma (PRP), the effects of garadacimab, abelacimab, asundexian, and milvexian and of commonly used anticoagulants apixaban, dabigatran, fondaparinux and heparins (enoxaparin and UFH).
METHODS: Anticoagulants were added to PRP at 6 concentrations and effects compared with UFH as a reference. The impact of adding anticoagulants into collection tubes before most preanalytical contact activation was also assessed. Concentrations achieving a 50% reduction in TG peak height (PH) were determined (IC50).
RESULTS: All anticoagulants prolonged lag time (LT) and reduced PH and endogenous thrombin potential, albeit to varying extents. UFH was the only anticoagulant able to suppress TG at clinically achieved concentrations (1 U/mL). The following IC50 were found: milvexian, 2400 ng/mL; apixaban and dabigatran, 175 ng/mL; fondaparinux, 2.4 μg/mL; enoxaparin, 0.5 U/mL; and UFH, 0.25 U/mL. Asundexian up to 5000 ng/mL failed to reduce TG PH by 50%. Adding garadacimab and abelacimab to collection tubes resulted in greater efficacy than when added to PRP: LT increased by 89% and 32%, respectively; IC50 were 25 and 12.5 μg/mL, respectively.
CONCLUSION: Heparins were by far the most effective anticoagulants in our in vitro model. FXIIa and FXI(a) inhibitors did not adequately prevent coagulation on the studied artificial surface. Direct oral anticoagulants and fondaparinux showed limited efficacy, aligning with clinical observations.