Identiﬁcation of Prothrombin Belgrade Variant in a Mexican-American Family with Recurrent Deep Vein Thrombosis

Sep 28, 2026

A rare prothrombin variant (c.1787G>A, p.Arg596Gln), also called the prothrombin Belgrade variant, is linked to increased thrombosis predisposition through resistance to antithrombin. In this case report, the first described heterozygous occurrence in a Mexican-American family is presented, alongside recurrent early-onset venous thromboembolism despite negative standard hypercoagulable studies. Findings suggest that comprehensive genetic thrombophilia testing should be considered in recurrent VTE with strong personal and/or family history but negative routine evaluations, especially in understudied ethnic backgrounds.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages4

Reading Time10 min

AccessFree to download

Abstract

Introduction

Venous thromboembolism and hereditary risk assessment

Case Summaries

Case 1

THIEME Article published online: 2025-12-22 Case Report 1 Identiﬁcation of Prothrombin Belgrade Variant in a Mexican–American Family with Recurrent Deep Vein Thrombosis Émile Moura Coelho da Silva1,2 Natalie Montanez 1 Miguel Escobar 1 1 Gulf States Hemophilia and Thrombophilia Center, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, Texas, United States 2 Department of Neurology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, Texas, United States TH Open 2025;9:a27665989 . Address for correspondence Émile Moura Coelho da Silva, MS, 7000 Fannin Street, Suite 750, Houston, TX 77007, United States (e-mail: [emilemouraa@gmail.com](emilemouraa@gmail.com)). Abstract Keywords ► F2 gene variant ► prothrombin ► thrombophilia ► venous thromboembolism A rare prothrombin variant (c.1787G >A, p.Arg596Gln), also known as the prothrombin Belgrade variant, has been associated with an increased predisposition to thrombosis through resistance to antithrombin. This variant has been previously reported in individuals from Serbia, Japan, China, and India. In this case report, we described the ﬁrst reported case of heterozygosity for the prothrombin Belgrade variant in a Mexican–American family. Affected individuals had negative results on standard hypercoagulable studies; however, they exhibited a history of early-onset and recurrent venous thromboembolism (VTE) . Although rare, the prothrombin Belgrade variant—and other prothrombin variants associated with antithrombin resistance—may be underrecognized in patients with recurrent thrombotic events, particularly among individuals from ethnic backgrounds not previously associated with this variant. These ﬁndings support the consideration of comprehensive genetic thrombophilia testing, including full sequencing of the prothrombin gene, in patients with negative standard hypercoagulable studies but a strong personal and/or family history of VTE. Introduction Venous thromboembolism (VTE) affects approximately 1 in 1,000 individuals annually.1 While VTE is multifactorial in origin, a hereditary cause should be suspected in patients with early-onset VTE (typically before age 40 or 50), a strong family history, recurrent episodes, or thrombosis in unusual locations, such as the central nervous system.2 Standard hereditary thrombophilia evaluation includes testing for protein S, protein C, antithrombin deﬁciency, and the factor V Leiden and prothrombin G20210A variants.3 However, additional genetic variants associated with thrombosis risk have been identiﬁed, including several variants in theprothrombin (F2 ) gene that confer antithrombin resis- received August 20, 2025 accepted after revision December 5, 2025 DOI [https://doi.org/](https://doi.org/)[ ](https://doi.org/)[10.1055/a-2766-5989.](10.1055/a-2766-5989.)[ ](10.1055/a-2766-5989.)[ISSN](ISSN 2512-9465.)[ 2512-9465.](ISSN 2512-9465.) tance.4–6 One such variant is the prothrombin Belgrade (c. 1787G>A, p.Arg596Gln), previously reported in individuals from Serbia, Japan, China, and India.4,7–9 We report the ﬁrst known case of this variant in a Mexican–American family with a history of recurrent VTE. This study was conducted in accordance with the principles of the Declaration of Helsinki. As the work consists of case reports and does not constitute systematic research on human subjects, it was exempt from Institutional Review Board review, and individual informed consent was formally waived. Nevertheless, informed consent was obtained from two of the three participants; the third participant could not be reached despite multiple attempts. © 2025 . The Author(s) . This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited.([https://creativecommons.org/licens

FAQs

What is the prothrombin Belgrade variant discussed in the report?

It is a rare F2 gene variant (c.1787G>A, p.Arg596Gln) associated with increased thrombosis risk through antithrombin resistance.

What were the standard hypercoagulable study results in the affected individuals?

The affected individuals had negative results on standard hypercoagulable testing despite a history of early-onset and recurrent venous thromboembolism.

Why do the authors recommend comprehensive genetic thrombophilia testing?

They suggest it can identify prothrombin variants linked to antithrombin resistance, particularly when routine studies are negative but personal and/or family history strongly suggests inherited thrombophilia.

Sep 28, 2026

Uploaded by mieayamfan