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Micro-volume thrombin generation test in plasma from animal species for studies of FXIa thrombogenicity

Thursday, October 11, 2012 — Poster Session III

10:00 a.m. – Noon

Natcher Conference Center, Building 45




  • Y Liang
  • S. A Woodle
  • E Struble
  • T. K Lee
  • D Scott
  • M Ovanesov


Thromboembolic events (TEE), including deep venous thrombosis and myocardial infarction, have been reported in patients receiving intravenous immunoglobulin. Recent research showed that many TEE-induced immunoglobulin samples contained procoagulant impurity coagulation factor XIa (FXIa). At present there is no systematic investigation of animal models that can be used to assess FXIa-dependent thrombogenicity risk in animals and be predictive for human response. To assist in species selection for in vivo animal studies, we developed a micro-volume variant of the thrombin generation assay and studied responses of animal species to human FXIa. In our assay, thrombin generation in plasma (20 microliters) is initiated by physiological activator tissue factor in the presence of procoagulant phospholipids, sample (FXIa), buffer and calcium (volume of all additions, 20 microliters). The thrombin generation response to human FXIa was comparable in most animal species, however, the minimal thrombogenic concentration ranged over 7 orders of magnitude, from below 1 pM in human plasma to 10-100 nM in the least sensitive animals. These findings will help to clarify differences in minimal thrombogenic doses of FXIa observed in various animal models and levels of FXIa associated with thrombotic events in humans.

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