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Thromb Haemost 2002; 87(06): 978-984
DOI: 10.1055/s-0037-1613121
Review Article
Schattauer GmbH

Anticoagulant and Membrane-degrading Effects of Secretory (Non-pancreatic) Phospholipase A2 Are Inhibited in Plasma

Didier Billy   *
2   Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, Central
,
Han Speijer
2   Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, Central
,
Robert F. A. Zwaal
2   Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, Central
,
Erik C. Hack
1   Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, Amsterdam, The Netherlands
,
Wim T. Hermens
2   Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, Central
› Author Affiliations
Further Information

Publication History

Received 30 April 2001

Accepted after resubmission 11 February 2002

Publication Date:
08 December 2017 (online)

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Summary

Plasma concentrations of secretory (non-pancreatic) phospholipase A2 (sPLA2) may rise 1000-fold during inflammation, and this acute phase response has been related to anticoagulant effects. In the present study this hypothesis was further investigated.

Prothrombinase activity was measured for model membranes mimicking the phospholipid composition of the outer membrane of resting and activated blood platelets. Using ellipsometry, membrane degradation by sPLA2 could be measured simultaneously with inhibition of thrombin production. The same technique was used to study clotting, by the sudden appearance of fibrin strands on the membrane. Results were compared with the effects of sPLA2 on the activation of washed platelets and platelets in plasma.

In buffer solution, model membranes were degraded by (patho)physiological concentrations of sPLA2. Even when only partially degraded, membranes rapidly lost their prothrombinase activity, indicating preferential degradation of phosphatidylserine. Addition of diluted plasma interfered with membrane degradation, and also with inhibition of prothrombinase activity. In agreement with these observations, sPLA2 inhibited thrombin production and annexin V-binding of activated washed platelets, but had no effects on platelet activation or clotting in plasma. These findings indicate that the elevated plasma sPLA2 concentrations observed in inflammatory disease will not reduce hypercoagulability in such patients.

Keywords

Phospholipase A2 - prothrombinase - anticoagulation - platelets - ellipsometry

* Present address: Medtronic Bakken Research Center, Endepolsdomein 5, 6229 GW Maastricht, The Netherlands


 

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