Presentation Details
| Novel Thrombophilia- Prothrombin Belgrade Variant in a Mexican Family Natalie/A Montanez1, 3, Miguel/A Escobar1, 2, 3. 1University of Texas Health Science Center of Houston, McGovern Medical School, Department of Pediatrics, Houston, TX, USA.2University of Texas Health Science Center of Houston, McGovern Medical School, Department of Internal Medicine, Houston, TX, USA.3Gulf States Hemophilia and Thrombophilia Center, Houston, TX, USA |
Abstract
Background: The F2 gene encodes the prothrombin protein, which plays an essential role in hemostasis. A rare prothrombin variant (c.1787G>A, p. Arg596Leu), also known as Belgrade prothrombin, results in predisposition to thrombosis via disruption of thrombin-antithrombin binding. This variant has only previously been reported in individuals from Serbia, Japan, China, and India with no case reports outside of these geographical areas. Inheritance pattern is autosomal dominant. Objectives: We present the first case of a Mexican family with recurrent venous thromboembolism (VTE) associated with the prothrombin Belgrade variant with previously negative routine hypercoagulable studies. Methods: Retrospective electronic medical record review of two Mexican female siblings found to have prothrombin Belgrade variant (c.1787G>A, p. Arg596Leu). Results: Patient 1. A 34-year-old female with initial thrombotic event at age 22 – seemingly unprovoked left common femoral, superficial femoral, deep femoral, popliteal, posterior tibial and peroneal deep vein thrombosis. Other thrombotic events include age 29- right upper extremity superficial thrombophlebitis (antepartum); right lower extremity deep vein thrombosis (postpartum) and age 31- recurrent left femoral and popliteal deep vein thrombosis (post stent placement). Initial hypercoagulable studies including- functional levels of fibrinogen, antithrombin, protein C and S, factor V Leiden mutation, prothrombin G20210A mutation, and antiphospholipid antibodies resulted in negative findings. Comprehensive hereditary thrombophilia gene panel, including full gene analysis of F2 resulted in heterozygosity for prothrombin Belgrade variant (c.1787G>A, p. Arg596Leu). Patient 2. A 26-year-old female with initial thrombotic event at age 13 – seemingly unprovoked occlusive venous thrombus extending from the left iliac vein to the popliteal. Other thrombotic events include ages 21, 22, 23, 25- recurrent deep vein thrombosis in the left common femoral, superficial femoral, popliteal vein and paired posterior tibial veins. Initial hypercoagulable studies resulted in negative findings. Targeted familial variant testing for prothrombin Belgrade variant (c.1787G>A, p. Arg596Leu) was positive. Additional targeted familial variant testing resulted in heterozygosity for prothrombin Belgrade variant (c.1787G>A, p. Arg596Leu) in father and brother, both with personal history of recurrent VTE. Conclusion: Although rare, prothrombin Belgrade may be present relatively frequently in patients with a personal and/or family history of VTE, and in individuals of ethnicities not previously reported. Therefore, it may be important to consider pursuing comprehensive genetic thrombophilia testing in the setting of negative standard hypercoagulable studies with history of recurrence and positive family history.
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