Activated Protein C Increases Fibrin Clot Lysis by Neutralization of Plasminogen Activator Inhibitor No Evidence for a Cofactor Role of Protein S

N J de Fouw; Y F de Jong; F Haverkate; R M Bertina

doi:10.1055/s-0038-1647055

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1988; 60(02): 328-333
DOI: 10.1055/s-0038-1647055

Original Article

Schattauer GmbH Stuttgart

Activated Protein C Increases Fibrin Clot Lysis by Neutralization of Plasminogen Activator Inhibitor No Evidence for a Cofactor Role of Protein S

Authors

N J de Fouw

¹The Gaubius Institute TNO, University Hospital, Leiden, The Netherlands

²The Haemostasis and Thrombosis Research Unit, University Hospital, Leiden, The Netherlands
Y F de Jong

¹The Gaubius Institute TNO, University Hospital, Leiden, The Netherlands

²The Haemostasis and Thrombosis Research Unit, University Hospital, Leiden, The Netherlands
F Haverkate

¹The Gaubius Institute TNO, University Hospital, Leiden, The Netherlands
R M Bertina

²The Haemostasis and Thrombosis Research Unit, University Hospital, Leiden, The Netherlands

Abstract

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summary

The effect of purified human activated protein G (APC) on fibrinolysis was studied using a clot iysis system consisting of purified glu-plasminogen, tissue-type plasminogen activator, plasminogen activator inhibitor (released from endothelial cells or blood platelets), fibrinogen, ¹²⁵T-fibrinogen and thrombin. All proteins were of human origin.

In this system APC could increase fibrinolysis in a dose dependent way, without affecting fibrin formation or fibrin crosslinking. However, this profibrinolytic effect of APC could only be observed when plasminogen activator inhibitor (PAI-l) was present. The effect of APC was completely quenched by pretreatment of APC with anti-protein C IgG or di-isopropylfluorophosphate. Addition of the cofactors of APC:protein S, Ca²⁺-ions and phospholipid-alone or in combination did not enhance the profibrinolytic effect of APC. These observations indicate that human APC can accelerate in vitro clot lysis by the inactivation of PAI-1 activity. However, the neutralization of PAI-1 by APC is independent of the presence or absence of protein S, phospholipid and Ca²⁺-ions.

Keywords

Activated protein C - Plasminogen activator inhibitor-1 - Protein S - Fibrinolysis

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References

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