Thromb Haemost 2000; 84(04): 604-610
DOI: 10.1055/s-0037-1614075
Review Article
Schattauer GmbH

Characterization of Cleaved Plasma Protein S with a Monoclonal Antibody-based Assay

Olivier Morbœuf*
1   From the Unité INSERM 428, Faculte de Pharmacie, France
,
Delphine Borgel
1   From the Unité INSERM 428, Faculte de Pharmacie, France
,
Pascale Gaussem
1   From the Unité INSERM 428, Faculte de Pharmacie, France
,
Anne Vincenot
1   From the Unité INSERM 428, Faculte de Pharmacie, France
,
Jean-Louis Pittet
2   Laboratoires bioMérieux, département d’hémostase, Marcy-l’Etoile, France
,
Martine Aiach
1   From the Unité INSERM 428, Faculte de Pharmacie, France
,
Sophie Gandrille
1   From the Unité INSERM 428, Faculte de Pharmacie, France
› Author Affiliations
Further Information

Publication History

Received 11 August 1999

Accepted after resubmission 11 May 2000

Publication Date:
11 December 2017 (online)

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Summary

A monoclonal antibody (mAb 5A5G2) recognized cleaved plasma protein S (PS) but not uncleaved PS. Interestingly, mAb 5A5G2 did not recognize thrombin-cleaved recombinant PS. Microsequencing of cleaved plasma PS showed a Q-S-T-N amino-terminal sequence, inferring cleavage after the Arg 60 residue. The mAb epitope was located within the sequence encompassing residues 61 to 73, i. e. the carboxyterminal part of the thrombin-sensitive region (TSR). We used this mAb to develop an ELISA assay to quantify in vivo cleaved PS. In plasma from 10 normal subjects, about 10% of PS was cleaved (7.1% to 15.4%), with a more than 2-fold increase in the corresponding sera. We found increased levels of cleaved PS in 8 patients with disseminated intravascular coagulation (DIC) and decreased levels in 22 patients on long-term oral anticoagulant therapy, whereas cleaved PS levels were similar in 8 hemophiliacs and the 10 normal subjects. Cleaved PS levels did not correlate with prothrombin fragment 1+2 levels released after cleavage by FXa in any of the groups, suggesting that circulating FXa is not the main factor involved in the production of cleaved PS in vivo.

* Olivier Morbœuf was the recipient of a grant from Ministère de l’Education Nationale, de la Recherche et de la Technologie.