Multiple concomitant thrombophilic gene mutations increase the risk of thrombosis

Introduction Thrombosis, involving both venous and arterial types, is a complex condition influenced by acquired and genetic factors. It substantially increases the risk of venous thromboembolism (VTE) and stroke. While the predictive importance of individual risk factors varies, patients with multiple genetic abnormalities face an increased risk. Method Multiple case presentations [ 1 ] [ 2 ]. Aims: This report details the clinical cases of four female family members with inherited thrombophilia, with three of them experiencing thrombotic events during childhood or young adulthood. Results The first is a 13-year-old girl with splenic infarction, and her asymptomatic twin also shares the same genetic risks. The third family member is a 29-year-old woman with a history of bilateral deep venous thrombosis (DVT), chronic venous insufficiency (CVI), and a stroke shortly after childbirth. The fourth is a 33-year-old woman with known thrombophilia, post-thrombotic syndrome, and CVI. Genetic testing revealed more than three gene defects in the family, including heterozygous Factor V Leiden, two MTHFR variants, homozygous PAI-1 4G/4G, and EPCR A2/A3, with PROS1 sequencing yielding negative results. Conclusion Performing thorough coagulation and genetic assessments is essential in familial thrombosis cases to enable early identification of risks and to facilitate the adoption of effective preventive measures. Publication History Article published online: 17 February 2026 © 2026. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany