Brinkman Herm Jan M, Ahnström Josefin, Castoldi Elisabetta, Dahlbäck Björn, Marlar Richard A
Department of Molecular and Cellular Hemostasis, Sanquin Research, Amsterdam, the Netherlands.
Centre for Haematology, Imperial College London, London, UK.
J Thromb Haemost. 2021 Jan;19(1):281-286. doi: 10.1111/jth.15108.
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.
蛋白S（PS）的遗传性缺陷会增加血栓形成的风险。然而，由于其多种生理相互作用，评估血浆PS水平变得复杂，而个体间的巨大差异使得建立可靠的临界值存在问题。PS具有多种生理功能，其中只有两种似乎具有显著的抗凝特性：活化蛋白C（APC）和组织因子途径抑制剂α（TFPIα）辅因子活性。目前临床实验室对PS功能缺陷的检测仅依赖于APC依赖性活性。本通讯提出了对PS定性缺陷进行重新分类的观点，以区分PS的两种主要抗凝功能。在仅基于抗凝表型对PS缺乏进行特异性诊断时，可靠的检测方法对于准确评估PS功能是必要的。本报告强调了PS的多效抗凝功能，并提出了在临床实验室中实施这些功能的循证建议。
