Pleiotropic Anticoagulant Functions of Protein S, Consequences for the Clinical Laboratory. Communication from the SSC of the ISTH

Authors

Herm Jan M. Brinkman, Department of Molecular and Cellular Hemostasis, Sanquin Research, Amsterdam, the Netherlands
Josefin Ahnström, Centre for Haematology, Imperial College London, London, UK
Elisabetta Castoldi, Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, the Netherlands
Björn Dahlbäck, Department of Translational Medicine, Lund University, Malmō, Sweden
Richard A. Marlar, Department of Pathology, University of New Mexico, TriCore Reference Laboratories, Albuquerque, NM, USA

Document Type

Article

Publication Date

1-1-2021

Abstract

Hereditary deficiencies of protein S (PS) increase the risk of thrombosis. However, assessing the plasma levels of PS is complicated by its manifold physiological interactions, while the large inter-individual variability makes it problematic to establish reliable cut-off values. PS has multiple physiological functions, with only two appearing to have significant anticoagulant properties: the activated protein C (APC) and tissue factor pathway inhibitor alpha (TFPIα) cofactor activities. Current clinical laboratory investigations for deficiency in PS function rely only on the APC-dependent activity. This communication presents an argument for reclassifying the qualitative PS deficiencies to differentiate the two major anticoagulant functions of PS. Reliable assays are necessary for accurate evaluation of PS function when making a specific diagnosis of PS deficiency based on the anticoagulant phenotype alone. This report emphasizes the pleiotropic anticoagulant functions of PS and presents evidence-based recommendations for their implementation in the clinical laboratory.

Recommended Citation

Brinkman HJM, Ahnström J, Castoldi E, Dahlbäck B, Marlar RA. Pleiotropic anticoagulant functions of protein S, consequences for the clinical laboratory. Communication from the SSC of the ISTH. J Thromb Haemost. 2021 Jan;19(1):281-286. doi: 10.1111/jth.15108. PMID: 33405384.