Multigene panel for thrombophilia testing in venous thromboembolism

Abstract

Background: Conventional tests for inherited thrombophilia focus on the 5 most-established inherited thrombophilias; ie deficiencies in antithrombin, protein C, and protein S, and the factor V Leiden and prothrombin G20210A variants. These tests identify thrombophilia in approximately 40% of tested patients with venous thromboembolism (VTE). Next-generation sequencing allows to detect variants in multiple coagulation-related genes, yet its clinical value for VTE remains unknown.

Objectives: This study aimed to report the findings from a multigene coagulation panel for VTE and assess its complementarity to conventional thrombophilia testing in clinical practice.

Methods: We conducted a single-center retrospective analysis of VTE patients tested with the Thrombosis-Hemostasis multigene (THG) panel, comprising 31 diagnostic-grade genes involved in thrombosis and hemostasis, from January 2019 to December 2023. We compared the results of the THG panel with conventional tests and analyzed characteristics associated with positive gene panel results.

Results: The THG panel identified genetic variants in 63% of 194 VTE patients. Half of the variants were classified as (likely) pathogenic variants ((L)PVs). Thirty-six (19%) cases carried variants in multiple genes. Among the 185 patients with available conventional test results, the THG panel detected noncompatible variants ([L]PVs or variants of unknown significance) in 76 patients (41%), which would remain undetected by performing conventional tests. Strictly concordant genetic findings were observed in 92 cases (50%).

Conclusion: The use of the THG panel provides more insights into the underlying thrombophilia of patients with VTE; however, its implications for patient management require further investigation.

Keywords: genetic testing; multigene panel; thrombophilia; venous thromboembolism.