Thromb Haemost 1994; 71(03): 331-338
DOI: 10.1055/s-0038-1642439
Original Article
Schattauer GmbH Stuttgart

A New Assay Based on Thrombin Generation Inhibition to Detect Both Protein C and Protein S Deficiencies in Plasma

Jérôme Duchemin
The INSERM CJF 91-01, UFR des Sciences Pharmaceutiques et Biologiques, Université Paris V, Paris, France
,
Jean-Louis Pittet
1  The Société bioMérieux, Marcy-l'Etoile, France
,
Michel Tartary
The INSERM CJF 91-01, UFR des Sciences Pharmaceutiques et Biologiques, Université Paris V, Paris, France
,
Suzette Béguin
2  The Department of Biochemistry (Pr H. C. Hemker), Cardiovascular Research Institute Maastricht and Faculty of Medicine, Maastricht, The Netherlands
,
Pascale Gaussem
The INSERM CJF 91-01, UFR des Sciences Pharmaceutiques et Biologiques, Université Paris V, Paris, France
,
Martine Alhenc-Gelas
The INSERM CJF 91-01, UFR des Sciences Pharmaceutiques et Biologiques, Université Paris V, Paris, France
,
Martine Aiach
The INSERM CJF 91-01, UFR des Sciences Pharmaceutiques et Biologiques, Université Paris V, Paris, France
› Author Affiliations
Further Information

Publication History

Received: 27 August 1993

Accepted after revision 12 September 1993

Publication Date:
06 July 2018 (online)

Summary

Activated protein C reduces thrombin generation by inactivating factors V and VIII in the presence of protein S. This prompted us to develop an assay which would allow specific exploration of this reaction. The total amount of thrombin formed in plasma after activation by tissue factor and phospholipids was reduced by adding thrombomodulin. This addition allowed protein C to be activated by endogenous thrombin. The inhibition of thrombin generation (ITG) due to protein C activation could be measured by comparing thrombin formation in the presence and in the absence of thrombomodulin. ITG increased with both protein C and protein S concentrations. Normal values of ITG expressed as a percentage were between 40 and 65% and were not influenced by age or sex. ITG increased in patients under heparin therapy, decreased in patients under oral anticoagulant therapy and was decreased in women using oral contraceptives. This method could be used for screening patients for protein C and protein S deficiencies.