Resistance to activated protein C, the FV: Q506 allele, and venous thrombosis

B. Dahlbäck; A. Hillarp; S. Rosen; B. Zöller

doi:10.1055/s-0038-1655322

Hämostaseologie, Inhaltsverzeichnis

Hamostaseologie 1998; 18(01): 1-10
DOI: 10.1055/s-0038-1655322

Übersichtsarbeiten/Review Article

Schattauer GmbH

Resistance to activated protein C, the FV: Q⁵⁰⁶ allele, and venous thrombosis

B. Dahlbäck

¹Department of Clinical Chemistry, Lund University, University Hospital, Malmö, Sweden

,

A. Hillarp

¹Department of Clinical Chemistry, Lund University, University Hospital, Malmö, Sweden

,

S. Rosen

²Chromogenix, Mölndal, Sweden

,

B. Zöller

¹Department of Clinical Chemistry, Lund University, University Hospital, Malmö, Sweden

› Institutsangaben

Abstract

Summary

Vitamin K-dependent protein C is an important regulator of blood coagulation. After its activation on the endothelial cell surface by thrombin bound to thrombomodulin, it cleaves and inactivates procoagulant cofactors Va and Villa, protein S and intact factor V working as cofactors. Until recently, genetic defects of protein C or protein S were, together with antithrombin III deficiency, the established major causes of familial venous thromboembolism, but they were found in fewer than 5-10% of patients with thrombosis. In 1993, inherited resistance to activated protein C (APC) was described as a major risk factor for venous thrombosis. It is found in up to 60% of patients with venous thrombosis. In more than 90% of cases, the molecular background for the APC resistance is a single point mutation in the factor V gene, which predicts substitution of an arginine (R) at position 506 by a glutamine (Q). Mutated factor V (FV: Q⁵⁰⁶) is activated by thrombin or factor Xa in normal way, but impaired inactivation of mutated factor Va by APC results in life-long hypercoagulability. The prevalence of the FV:Q⁵⁰⁶ allele in the general population of Western countries varies between 2 and 15%, whereas it is not found in several other populations with different ethnic backgrounds. Owing to the high prevalence of FV:Q⁵⁰⁶ in Western populations, it occasionally occurs in patients with deficiency of protein S, protein C, or antithrombin III. Individuals with combined defects suffer more severely from thrombosis, and often at a younger age, than those with single defects, suggesting severe thrombophilia to be a multigenetic disease.

Keywords

APC-resistance - factor V - protein C - protein S - thrombosis

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Referenzen

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