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Thromb Haemost 2003; 89(03): 438-445
DOI: 10.1055/s-0037-1613371
Blood Coagulation, Fibrinolysis and Cellular Haemostasis
Schattauer GmbH

Local tissue factor pathway inhibitor release in the human forearm

Michiel J. B. Kemme
3   Centre for Human Drug Research, Leiden, The Netherlands
,
Jacobus Burggraaf
3   Centre for Human Drug Research, Leiden, The Netherlands
,
Rik C. Schoemaker
3   Centre for Human Drug Research, Leiden, The Netherlands
,
Adam F. Cohen
3   Centre for Human Drug Research, Leiden, The Netherlands
,
Cornelis Kluft
1   Gaubius Laboratory, TNO-PG, Leiden, The Netherlands
,
Stanley Chia
2   Clinical Pharmacology Unit and Research Centre, University of Edinburgh, Western General Hospital, Edinburgh, Scotland, UK
,
David J. Webb
2   Clinical Pharmacology Unit and Research Centre, University of Edinburgh, Western General Hospital, Edinburgh, Scotland, UK
,
David E. Newby
2   Clinical Pharmacology Unit and Research Centre, University of Edinburgh, Western General Hospital, Edinburgh, Scotland, UK
› Author Affiliations
Further Information

Publication History

Received 05 September 2002

Accepted after revision 30 December 2002

Publication Date:
09 December 2017 (online)

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Summary

Nineteen healthy men received unilateral brachial artery infusions of either unfractioned heparin (0.3-100 IU/min), saline or the endothelium-dependent vasodilators substance P (2-8 pmol/min) and bradykinin (100-1000 pmol/min), and the endothelium-independent vasodilator sodium nitroprusside (2-8 µg/min). Heparin caused a dose-dependent increase in plasma TFPI concentrations in both arms (ANOVA, p <0.0001). Estimated net forearm TFPI release was 7 ± 16, 29 ± 20 and 138 ± 72 ng/100 mL tissue/min during 10, 30 and 100 IU/min of heparin respectively (ANOVA, p <0.0001). Compared to the systemic circulation, the forearm sensitivity to heparin induced TFPI release was 3.6-fold lower (166 ± 67 ng/IU vs. 596 ± 252 ng/IU: t-test, p = 0.004). Substance P, bradykinin and sodium nitroprusside all caused substantial dose-dependent increases in blood flow (ANOVA, p <0.001 for all) without affecting plasma TFPI concentrations. There are important regional differences in endothelial TFPI release, with the forearm circulation being relatively insensitive to heparin.

Keywords

Tissue factor pathway inhibitor - haemostasis - heparin - substance P - bradykinin
 

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