Factor XI Inhibition With Heparin Reduces Clot Formation in Simulated Pediatric Extracorporeal Membrane Oxygenation

Andrew D. Meyer*, Catherine R. Thorpe, Tamara Fraker, Tomas Cancio, Jeanette Rocha, R. Patrick Willis, Andrew P. Cap, David Gailani, Joseph J. Shatzel, Erik I. Tucker, Owen J.T. McCarty

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Extracorporeal membrane oxygenation (ECMO) supplies circulatory support and gas exchange to critically ill patients. Despite the use of systemic anticoagulation, blood exposure to ECMO surfaces causes thromboembolism complications. Inhibition of biomaterial surface-mediated activation of coagulation factor XI (FXI) may prevent device-associated thrombosis. Blood was collected from healthy volunteers (n = 13) following the U.S. Army Institute of Surgical Research standard operating procedure for testing in an ex vivo ECMO circuit. A roller-pump circuit circulated either 0.5 U/ml of unfractionated heparin alone or in combination with the anti-FXI immunoglobulin G (IgG) (AB023) for 6 hours or until clot formation caused device failure. Coagulation factor activity, platelet counts, time to thrombin generation, peak thrombin, and endogenous thrombin potential were quantified. AB023 in addition to heparin sustained circuit patency in all tested circuits (5/5) after 6 hours, while 60% of circuits treated with heparin alone occluded (3/8), log-rank p < 0.03. AB023 significantly prolonged the time to clot formation as compared to heparin alone (15.5 vs. 3.3 minutes; p < 0.01) at the 3-hour time point. AB023 plus heparin significantly reduced peak thrombin compared to heparin alone (123 vs. 217 nM; p < 0.01). Inhibition of contact pathway activation of FXI may be an effective adjunct to anticoagulation in extracorporeal life support.

Original languageEnglish
Pages (from-to)1074-1082
Number of pages9
JournalASAIO Journal
Volume69
Issue number12
DOIs
StatePublished - 1 Dec 2023
Externally publishedYes

Keywords

  • biomaterials
  • blood coagulation
  • ECMO
  • factor XI
  • thrombin

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