Review Article

Ann Lab Med 2013; 33(1): 8-13

Published online January 1, 2013

Copyright © Korean Society for Laboratory Medicine.

Activated Protein C Anticoagulant System Dysfunction and Thrombophilia in Asia

Naotaka Hamasaki, M.D.1, Hiroyuki Kuma, Ph.D.1, and Hiroko Tsuda, M.D.2

Department of Clinical Chemistry1, Faculty of Pharmaceutical Sciences, Natagaki International University, Nagasaki; Department of Nutrition Sciences2, Nakamura Gakuen University, Fukuoka, Japan

Correspondence to: Naotaka Hamasaki
Department of Clinical Chemistry, Faculty of Pharmaceutical Sciences, Nagasaki International University, Nagasaki 859-3298, Japan
Tel: +81-956-39-2020
Fax: +81-956-20-5622

Received: June 11, 2012; Revised: September 21, 2012; Accepted: November 15, 2012

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.


Thrombophilia that is common among Caucasians is caused by genetic polymorphisms of coagulation factor V Leiden (R506Q) and prothrombin G20210A. Unlike that in Caucasians, thrombophilia that is common in the Japanese and Chinese involve dysfunction of the activated protein C (APC) anticoagulant system caused by abnormal protein S and protein C molecules. Approximately 50% of Japanese and Chinese individuals who develop venous thrombosis have reduced activities of protein S. The abnormal sites causing the protein S molecule abnormalities are distributed throughout the protein S gene, PROS1. One of the most common abnormalities is protein S Tokushima (K155E), which accounts for about 30% of the protein S molecule abnormalities in the Japanese. Whether APC dysfunction occurs in other Asian countries is an important aspect of mapping thrombophilia among Asians. International surveys using an accurate assay system are needed to determine this.

Keywords: Venous thromboembolism, Activated protein C anticoagulant system, Asian thrombophilia, Deep vein thrombosis, Protein S, Quantitative assay of protein S