Fibrinolytic Response to lnterferon-a in Healthy Human Subjects

E P M Corssmit; M Levi; C E Hack; J W ten Cate; H P Sauerwein; J A Romijn

doi:10.1055/s-0038-1650230

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1996; 75(01): 113-117
DOI: 10.1055/s-0038-1650230

Original Article

Schattauer GmbH Stuttgart

Fibrinolytic Response to lnterferon-a in Healthy Human Subjects

E P M Corssmit

¹The Department of Internal Medicine, University of Amsterdam, The Netherlands

,

M Levi

¹The Department of Internal Medicine, University of Amsterdam, The Netherlands

²The Center for Haemostasis, Thrombosis, Atherosclerosis and Inflammation Research, University of Amsterdam, The Netherlands

,

C E Hack

⁴The Department of Autoimmune Diseases and Inflammation, Central Laboratory of the Netherlands Red Cross Blood Transfusion Service (CLB), Amsterdam, The Netherlands

,

J W ten Cate

²The Center for Haemostasis, Thrombosis, Atherosclerosis and Inflammation Research, University of Amsterdam, The Netherlands

,

H P Sauerwein

¹The Department of Internal Medicine, University of Amsterdam, The Netherlands

,

J A Romijn

³The Department of Intensive Care, Academic Medical Center, University of Amsterdam, The Netherlands

› Author Affiliations

Abstract

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Summary

Interferons (IFNs) are used for a variety of disorders. It has been postulated that part of the effects of IFN may be mediated by IFN-induced modulation of endothelial cells. Since the principal activating and inhibiting factors of the fibrinolytic system are synthesized and stored in endothelial cells, we have studied the effects on fibrinolysis and coagulation of the administration of recombinant IFN-α (5 × 10⁶U/m²) to healthy human subjects (n = 8) in a randomized controlled cross-over study. IFN-α significantly increased plasma levels of tissue-type plasminogen activator (t-PA) and urokinase-type plasminogen activator (u-PA). Simultaneously, plasma levels of the inhibitor of plasminogen activation, PAI-1, sharply increased. The net effect on plasma plasminogen activator activity (PA-activity) was a modest increase to 116% of baseline, however without a significant effect on plasmin generation, as reflected by plasma levels of plasmin-α₂-antiplasmin complexes. IFN-α had no effect on the plasma levels of thrombin-antithrombin III (TAT) complexes.

We conclude that despite considerable effects on endothelial cells, IFN-α does not significantly alter the coagulant-fibrinolytic balance, although the occurrence of such changes under pathological circumstances is not excluded.

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References

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