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Thromb Haemost 1996; 75(03): 445-449
DOI: 10.1055/s-0038-1650294
Original Article
Schattauer GmbH Stuttgart

Factor XIa Induced Activation of the Intrinsic Cascade In Vivo

Hugo ten Cate
1   The Dept. of Internal Medicine, Slotervaartziekenhuis, Amsterdam, The Netherlands
2   The Center for Hemostasis, Thrombosis, Atherosclerosis, and Inflammation Research, Amsterdam, The Netherlands
,
Bart J Biemond
2   The Center for Hemostasis, Thrombosis, Atherosclerosis, and Inflammation Research, Amsterdam, The Netherlands
3   Dept. of Internal Medicine, Academic Medical Center, Amsterdam, The Netherlands
,
Marcel Levi
2   The Center for Hemostasis, Thrombosis, Atherosclerosis, and Inflammation Research, Amsterdam, The Netherlands
3   Dept. of Internal Medicine, Academic Medical Center, Amsterdam, The Netherlands
,
Walter A Wuillemin
4   Central Laboratory of the Netherlands Red Cross Bloodtransfusion Service, Amsterdam, The Netherlands
,
Kenneth Bauer
5   Department of Medicine, Beth Israel Hospital, Amsterdam, The Netherlands
6   Brockton - West Roxbury Department of Veterans Affairs Medical Center, Harvard Medical School, Boston, Massachusetts, USA
,
Samad Barzegar
5   Department of Medicine, Beth Israel Hospital, Amsterdam, The Netherlands
,
Harry R Buller
1   The Dept. of Internal Medicine, Slotervaartziekenhuis, Amsterdam, The Netherlands
,
C Erik Hack
1   The Dept. of Internal Medicine, Slotervaartziekenhuis, Amsterdam, The Netherlands
,
Jan W ten Cate
2   The Center for Hemostasis, Thrombosis, Atherosclerosis, and Inflammation Research, Amsterdam, The Netherlands
,
Robert D Rosenberg
5   Department of Medicine, Beth Israel Hospital, Amsterdam, The Netherlands
7   The Department of Biology and Whitaker College of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA
› Author Affiliations
Further Information

Publication History

Received 26 June 1995

Accepted after resubmission 28 November 1995

Publication Date:
31 August 2018 (online)

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Summary

Coagulation factor XI is a glycoprotein of the contact factor system. Its deficiency is associated with a highly variable bleeding tendency, thus a role in relation to hemostasis appears to exist. However, the importance of factor XI for stimulating intrinsic coagulation in vivo has not yet been determined. To study the procoagulant effects of human factor Xla in vivo, we infused the purified enzyme into normal chimpanzees (100 Μg) in the absence or presence of the thrombin inhibitor rec-hirudin (1.0 mg/kg loading dose plus 0.3 mg/kg body wt continuous infusion). Factor Xla elicited an immediate activation of factors IX, X, and prothrombin, as measured by their respective activation fragments. However, whereas the activation of factors IX and X was immediate and shortlasting, (peak increments of 6- and 1.4-fold of baseline at 5 minutes after injection), the conversion of prothrombin gradually increased, reaching a summit of 6-fold baseline values after 60 min, and remaining elevated during the course of the experiments. Thrombin-antithrombin complexes also remained elevated during the study period. In the presence of hirudin, the initial activation of factors IX, X, and prothrombin was unchanged, however the further increment in prothrombin fragment FI+2 was markedly inhibited. These results demonstrate that factor Xla is a potential agonist of the intrinsic cascade in vivo, which activity is enhanced in the presence of thrombin.

 

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