Deficiency of natural anticoagulants

• Published in: SEIBUTSU BUTSURI KAGAKU Vol. 38; no. 6; pp. 397 - 402
• Main Authors: Niiya, Kenji, Hayakawa, Yumiko, Sakuragawa, Nobuo, Hayashi, Tomohiro
• Format: Journal Article
• Language: English
• Published: Japanese Electrophoresis Society 1994
• Subjects: antithrombin; coagulation cascade; protein C; protein S; thrombotic disease
• ISSN: 0031-9082; 1349-9785
• DOI: 10.2198/sbk.38.397

Two major regulatory mechanisms operating in the blood coagulation cascade are known. One is the neutralization of thrombin by antithrombin (AT), the other is the proteolytic inactivation of procoagulant cofactors Va and VIIIa by activated protein C (APC). AT is a member of the serine protease inhibitors (SERPINs), and the major plasma inhibitor of activated serine proteinases including thrombin. After its binding to heparin-like substance on the vascular endothelial cells, the formation of complexes between thrombin and AT is accelerated by 1, 000-fold to efficiently inactivate thrombin. The zymogen protein C is converted to APC by a thrombin-thrombomodulin complex on the surface of endothelial cells. The formed APC downregulates the coagulation cascade by inactivation of Va and VIIIa in the presence of its cofactor protein S (PS), and also enhances the fibrinolytic system by inhibition of plasminogen activator inhibitor 1. The importance of these factors (AT, PC and PS) as natural anticoagulants is manifested by the clinical observations that the patients with congenital deficiency or abnormality of each factor are suffering from severe thrombotic disorders. Hence, measurements of the factors in the patients with thrombotic diseases are of most important in understanding pathophysiology of the diseases.