See also Mannucci PM. Red cells playing as activated platelets in thalassemia intermedia. This issue, pp 2149–51. Summary. Background: Hypercoagulability in splenectomized patients with thalassemia intermedia (TI) has been extensively evaluated. However, clinical and laboratory characteristics of patients who eventually develop overt thromboembolic events (TEE) are poorly studied. Patients/Methods: Three Groups of TI patients (n = 73 each) were retrospectively identified from a registry involving six centers across the Middle East and Italy: Group I, all splenectomized patients with a documented TEE; Group II, age‐ and sex‐matched splenectomized patients without TEE; and Group III, age‐ and sex‐matched non‐splenectomized patients without TEE. Retrieved data included demographics, laboratory parameters, clinical complications, and received treatments that may influence TEE development, and reflected the period prior to TEE occurrence in Group I. Results: The mean age of Group I patients at development of TEE was 33.1 ± 11.7 years, with a male to female ratio of 33:40. TEE were predominantly venous (95%) while four patients (5%) had documented stroke. Among studied parameters, Group I patients were more likely to have a nucleated red blood cell (NRBC) count ≥ 300 × 10⁶ L⁻¹, a platelet count ≥ 500 × 10⁹ L⁻¹ and evidence of pulmonary hypertension (PHT), or be transfusion naïve. The median time to thrombosis following splenectomy was 8 years. Patients with an NRBC count ≥ 300 × 10⁶ L⁻¹, a platelet count ≥ 500 × 10⁹ L⁻¹, or who were transfusion naive also had a shorter time to thrombosis following splenectomy. Conclusion: Splenectomized TI patients who will develop TEE may be identified early on by high NRBC and platelet counts, evidence of PHT, and transfusion naivety.