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. 2025 Oct;23(10):3173-3184.
doi: 10.1016/j.jtha.2025.06.016. Epub 2025 Jun 18.

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

Michael Hardy  1 , Henri Thonon  2 , Jonathan Douxfils  3 , Julie Vassart  4 , Isabelle Gouin-Thibault  5 , Sarah Lessire  6 , Thomas Lecompte  7 , François Mullier  8
Affiliations

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

Michael Hardy et al. J Thromb Haemost. 2025 Oct.

Abstract

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.

Keywords: catheter; direct oral anticoagulants; factor XI inhibitors; heparin; thrombin generation.

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Conflict of interest statement

Declaration of competing interests H.T., J.V, I.G.-T., S.L., T.L.: none. M.H. reports research grants from the Belgian National Fund for Scientific Research and from the Fondation Mont-Godinne. J.D. reports honoraria from Gedeon Richter Benelux and Mithra Pharmaceuticals outside the submitted work. He is also the CEO and founder of QUALIblood, s.a., a contract research organization manufacturing the DP-Filter. F.M. reports speaker fees from Diagnostica Stago (Asnières-sur-Seine, France) outside the submitted work.

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