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Thromb Haemost 1997; 77(05): 0905-0910
DOI: 10.1055/s-0038-1656076
Coagulation
Schattauer GmbH Stuttgart

The Coagulation and Fibrinolytic Responses of Baboons after In Vivo Thrombin Generation – Effect of Interleukin 6

Egbert K O Kruithof
1   The Division of Angiology and Hemostasis, University Hospital, Geneva, Switzerland; Ares Serono, Geneva, Switzerland
,
Jean Claude Mestries
2   The Department of Radiobiology, CRSSA, La Tronche, France
,
Marie-Paule Gascon
3   The Preclinical Pharmacology Department, Ares Serono, Geneva, Switzerland
,
Arnaud Ythier
3   The Preclinical Pharmacology Department, Ares Serono, Geneva, Switzerland
› Author Affiliations
Further Information

Publication History

Received 17 September 1996

Accepted after resubmission 10 January 1997

Publication Date:
11 July 2018 (online)

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Summary

Disseminated intravascular coagulation (DIC) may lead to severe thrombotic or hemorrhagic complications. The present work was undertaken to study the effect of interleukin 6 (IL-6) on variations of key coagulation and fibrinolytic parameters in plasma in a baboon model of experimental DIC induced by injection of factor Xa and phospholipids at dosages leading to partial (48%) or complete fibrinogen depletion. Transient increases of D-dimer, fibrinopeptide A, thrombin-antithrombin and the activated partial thromboplastin time were observed. Each parameter had a particular (time and Xa/phospho- lipid dose dependent) pattern of changes. The principal effect of IL-6 was a more rapid restoration of fibrinogen concentrations and of overall coagulation tests. Injection of factor Xa/phospholipids led also to a rapid increase of tissue-type plasminogen activator (t-PA) the extent of which was dependent on Xa/phospholipid dose. Pretreatment with IL-6 induced a threefold increase of basal t-PA and a corresponding increase of the t-PA response. Plasminogen activator inhibitor type 1 (PAI-1) concentrations did not change after low dose Xa/phospholipids, but increased eightfold after high dose Xa/phospholipids. IL-6 pretreatment induced within 8 h a twentyfold increase of PAI-1 but no further increase was observed after injection of factor Xa/phospholipids.

Thus, in vivo thrombin generation leads to dynamic modifications of the coagulation and fibrinolytic systems. The principal effect of IL-6 is a more rapid normalization of overall coagulation tests, due to normalization of fibrinogen, and an increased t-PA release response which is partially counteracted by increased PAI-1 concentrations.

 

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