Thrombophilia testing and thrombotic risk evaluation in beta-thalassemia: A cohort analysis from a hub regional center

Abstract Background: β-thalassemia (βT) is a group of inherited hemoglobin synthesis disorders, characterized by defective β-chain synthesis. Clinical complications related to hemostasis, including pulmonary hypertension, venous thromboembolism (VTE), and ischemic arterial events, occur in βT with a prevalence between 1.1% and 5.3%. Thrombophilia might contribute to VTE in βT, but available data, quite scant, do not show an increased frequency of inherited thrombophilia in βT patients. Aims: This study aimed to investigate the clinical context and indications to thrombophilia screening in βT patients followed by the Hub Regional Center for Thalassemia in Palermo, Sicily. The prevalence of VTE or thromboembolic events (TEE) and its management were also evaluated Methods: A retrospective analysis was conducted on hospital records and patient charts of βT patients managed at our Center over the past five years, from January 2020 to January 2025, focusing on the clinical context and indications for thrombophilia screening type of assays performed, diagnosis of VTE or Thromboembolic events (TEE) and its management . Thrombophilia screening included: Factor V Leiden gene mutation, Fator II (G20210A) gene mutation; antithrombin, anticoagulant protein C ,anticoagulant protein S, Lupus anticoagulant (LA), anticardiolipin antibodies (aCL), anti-β2-glycoprotein-I (anti-β2GPI) antibodies, homocysteine. coagulation Factor VIII Results: Sixty-four βT patients underwent thrombophilia screening: 34 males, 31 females, with a mean age of 44 years (range 35-53), the most commonly reported comorbidities were hemocromatosis ,osteoporosis and liver disease; patients were mainly under regular transfusion (45/64) and iron chelation therapy ,13 subjects were treated with hydroxiurea . Eighteen patients underwent a complete thormbophilia screening, while 34/64 and 38/64 patients had a genetic and functional screening, respectively . Complete thrombophilia screening was mostly indicated by splenectomy (56%) and a personal history of VTE (100%). Thrombotic complications occurred in 17 subjects over five years:12 patient with thrombophilia had one VTE episode , 5 experienced a TEE due to atrial fibrillation (AF. Patients with FA received direct oral anticoagulants (DOACs, Edoxaban, N=3;Rivaroxaban, N=1 and Apixaban ,N=1) while patients with VTE were mainly managed with long term vitamn K antagonists (N=7) or Low Molecular Weight Heparin (N=5) for a mean of 4 months after a deep vein thrombosis (DVT) with complete recanalization. One patient (2.9%) was heterozygous for FII (G20210A) and three (4%) for FV Leiden. Elevated aCL and anti-β2GPI ewere detecetd in 7.5 % of patients. Conclusions:Thrombophilia screening is not routinely performed in βT patients but it is primarily requested for those with a history of VTE or before splenectomy. Patients with βT may be safely a treated with long-term direct oral anticoagulants or vitamin k antagonists.The low prevalence of common genetic mutations and antiphospholipid antibodies suggests that other factors may contribute more significantly to thrombotic risk in βT patients. Further research is needed to explore alternative genetic and acquired thrombophilic conditions in this population. Given the known morbidity caused by thrombotic events in βT, a personalized risk assessment in clinical practice must be pursued.