Activated Protein C Resistance: The Most Common Risk Factor for Venous Thromboembolism

Abstract

Background: Venous thromboembolism is a major cause of morbidity and mortality. Although activated protein C resistance (APC-R) is the most commonly recognized inherited risk factor for venous thromboembolism, little is known about its long-tenn implications on health.

Methods: MEDLINE was searched from January 1989 through August 1999 using the key words “thromboembolism,” “thrombosis,” “activated protein C resistance,” and “factor V Leiden.”

Results: One in 1000 people in the United States is affected by venous thromboembolism annually. APC-R is now understood to be responsible for up to 64% of these cases. APC-R, which occurs widely in some ethnic groups and is nearly absent in others, is due to a single point mutation in the gene for clotting factor V. As a result, inactivation of factor V by activated protein C is impaired, leading to a hypercoagulable state. This condition creates a lifelong increased risk of thrombosis and, possibly, anticoagulant therapy..

Conclusion: Family physicians have a new tool for assessing risks for venous thromboembolism. Recognizing that up to 64% of patients with venous thromboembolism can have APC-R and treating this disorder with prophylactic and therapeutic anticoagulation might reduce patient morbidity and mortality from venous thromboembolism. Screening high-risk patients might now be indicated.