Venous thromboembolism laboratory testing (factor V Leiden and factor II c.∗97G>A), 2025 revision: A technical standard of the American College of Medical Genetics and Genomics (ACMG)

Abstract

Venous thromboembolism (VTE) occurs when a blood clot forms in a vein. The etiology of VTE is multifactorial, including both environmental and genetic factors. Among the genetic factors, factor V Leiden and factor II c.∗97G>A (formerly referred to as prothrombin 20210G>A) are the 2 most common genetic variants associated with VTE. Testing for these variants is one of the most common referrals in clinical genetics laboratories. Although the methodologies for testing these 2 variants are relatively straightforward, the clinical implementation can be complicated regarding test indications, risk assessment for occurrence, and recurrence of VTE and related genetic counseling. This document provides an overview of VTE, information about the variants and their influence on risk, considerations before initiating genetic testing, and the clinical and analytical sensitivity and specificity of the tests. Key information that should be included in the laboratory report is also provided. This document supersedes the Technical Standards and Guidelines for Venous Thromboembolism Laboratory Testing originally published in 2005 and revised in 2018. It is designed for genetic testing professionals familiar with the disease and the analysis methods.

Keywords: Factor II; Factor V; Factor V Leiden; Thrombophilia; Venous thromboembolism.