| Title: |
Effect of heparins, DOACs, and FXII/FXI inhibitors on catheter-initiated thrombin generation in PRP: an in vitro study. |
| Authors: |
Hardy, Michaël; Thonon, Henri; Douxfils, Jonathan; Vassart, Julie; Gouin-Thibault, Isabelle; Lessire, Sarah; Lecompte, Thomas; Mullier, François |
| Contributors: |
UCL - (MGD) Service d'anesthésiologie; UCL - (MGD) Laboratoire de biologie clinique; UCL - (MGD) Centre de transfusion sanguine; UCL - (MGD) Services des urgences |
| Source: |
Journal of thrombosis and haemostasis : JTH, Vol. 23, no. 10, p. 3173-3184 (2025) |
| Publication Year: |
2025 |
| Collection: |
DIAL@USL-B (Université Saint-Louis, Bruxelles) |
| Subject Terms: |
anticoagulants; catheter; direct oral anticoagulants; factor XIa inhibitors; heparin; thrombin generation |
| Description: |
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 XII(a) and XI(a) inhibitors remains unexplored. We aim 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, milvexian, and commonly used anticoagulants apixaban, dabigatran, fondaparinux and heparins (enoxaparin, UFH). Anticoagulants were added to PRP at six 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). 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 2,400 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 5,000 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. Heparins were by far the most effective anticoagulants in our in vitro model. Factor XIIa and XI(a) inhibitors did not adequately prevent coagulation on the studied artificial surface. DOACs and fondaparinux showed limited efficacy, aligning with clinical observations. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
boreal:302455; https://hdl.handle.net/2078.1/302455; info:pmid/40541813 |
| DOI: |
10.1016/j.jtha.2025.06.016 |
| Availability: |
https://hdl.handle.net/2078.1/302455; https://doi.org/10.1016/j.jtha.2025.06.016 |
| Rights: |
info:eu-repo/semantics/openAccess |
| Accession Number: |
edsbas.247DD926 |
| Database: |
BASE |