Inactivation of Factor XIa in Vivo:
Studies in Chimpanzees and in Humans

Walter A Wuillemin; C Erik Hack; Wim K Bleeker; Bart J Biemond; Marcel Levi; Hugo ten Cate

doi:10.1055/s-0038-1650621

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1996; 76(04): 549-555
DOI: 10.1055/s-0038-1650621

Original Article

Schattauer GmbH Stuttgart

Inactivation of Factor XIa in Vivo: Studies in Chimpanzees and in Humans

Walter A Wuillemin

¹The Central Laboratory of the Netherlands Red Cross Blood Transfusion Service and Laboratory for Clinical and Experimental Immunology, University of Amsterdam, Amsterdam

,

C Erik Hack

¹The Central Laboratory of the Netherlands Red Cross Blood Transfusion Service and Laboratory for Clinical and Experimental Immunology, University of Amsterdam, Amsterdam

²Department of Internal Medicine, Free University Hospital, Amsterdam

,

Wim K Bleeker

¹The Central Laboratory of the Netherlands Red Cross Blood Transfusion Service and Laboratory for Clinical and Experimental Immunology, University of Amsterdam, Amsterdam

,

Bart J Biemond

³Center for Hemostasis, Thrombosis, Atherosclerosis, and Inflammation Research, Academic Medical Center, Amsterdam

,

Marcel Levi

³Center for Hemostasis, Thrombosis, Atherosclerosis, and Inflammation Research, Academic Medical Center, Amsterdam

,

Hugo ten Cate

³Center for Hemostasis, Thrombosis, Atherosclerosis, and Inflammation Research, Academic Medical Center, Amsterdam

⁴Slotervaart Ziekenhuis, Department of Internal Medicine, Amsterdam, The Netherlands

› Author Affiliations

Abstract

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Summary

C1-inhibitor (C1Inh), antithrombin III (ATIII), α₁-antitrypsin (a1AT), and α₂-antiplasmin (a2AP) are known inhibitors of factor XIa (FXIa). However, their precise contribution to FXIa inactivation in vivo is not known. We investigated FXIa inactivation in chimpanzees and assessed the contribution of these inhibitors to FXIa inactivation in patients with presumed FXI activation.

Chimpanzees were infused with FXIa and the various FXIa-FXIa inhibitor complexes formed were measured. Most of FXIa was complexed to C1Inh (68%), followed by a2AP (13%), a1AT (10%), and ATIII (9%). Analysis of the plasma elimination kinetics revealed a half-life time of clearance (t_1/2) for the FXIa-FXIa inhibitor complexes of 95 to 104 min, except for FXIa-a1AT, which had a t_1/2 of 349 min. Due to this long t_1/2, FXIa-a1AT complexes were predicted to show the highest levels in plasma samples from patients with activation of FXI. This was indeed shown in patients with disseminated intravascular coagulation, recent myocardial infarction or unstable angina pectoris. We conclude from this study that in vivo C1Inh is the predominant inhibitor of FXIa, but that FXIa-a1 AT complexes due to their relatively long t_1/2 may be the best parameter to assess FXI activation in clinical samples.

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References

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