Thromboembolic Events in Beta Thalassemia Major: An Italian Multicenter Study

Abstract

Thromboembolic (TE) events have been frequently reported in β-thalassemic patients in association with known risk factors such as diabetes, complex cardiopulmonary abnormalities, hypothyroidism, liver function anomalies, and postsplenectomy thrombocytosis. In a recent survey involving 9 Italian thalassemic centers, we identified 32 patients with TE episodes in a total of 735 subjects, of whom 683 had thalassemia major and 52 thalassemia intermedia, corresponding to 3.95 and 9.61%, respectively. There was a great variation in localization: the main one (16/32) was CNS, with a clinical picture of headache, seizures and hemiparesis. Other localizations were the pulmonary (3 patients), mesenteric (1 patient) and portal (2 patients) sites. There were 6 cases of deep venous thrombosis (2 in the upper limbs, 4 in the lower ones). Intracardiac thrombosis was found in 2 subjects and clinical and laboratory signs of DIC were observed in 2 others during pregnancy. Since our patients with TE events present a statistically significantly higher incidence of associated dysfunction (cardiomyopathy, diabetes, liver function anomalies, hypothyroidism) than those without TE events (50 vs. 13.8%), we suggest close monitoring of those patients who are at higher risk of developing TE events because of the presence of one or more of these predisposing factors.

The hypercoagulable state in thalassemia

“…The incidence was 3.95% among 685 ␤-TM patients and 9.61% among 52 patients with ␤-TI. 7 The same group reported a lower incidence (1.1%) of thromboembolic complications among 1146 patients with ␤-TM who were followed for 37 years. 7 Another study showed a 5.3% overall incidence of thrombotic complications among 495 patients with thalassemia whose median age was 28 years.…”

“…7 The same group reported a lower incidence (1.1%) of thromboembolic complications among 1146 patients with ␤-TM who were followed for 37 years. 7 Another study showed a 5.3% overall incidence of thrombotic complications among 495 patients with thalassemia whose median age was 28 years. 1,2 In this study, the prevalence of thromboembolic events was 3.3% among 421 patients with ␤-TM and 16.2% among 74 patients with ␤-TI, although 15.3% of these patients had predisposing congenital or acquired factors contributing to the hypercoagulability.…”

“…An Italian multicenter study of 735 patients with ␤-TM reported 16 individuals with cerebral thromboembolic events accompanied by a clinical picture of headache, seizures, and hemiparesis. 7 Cerebral thrombosis was also found in patients with ␤ thalassemia/ hemoglobin E disease and in ␣ thalassemia. 8,9 All these reports were from patients who were not given regular transfusions and were not associated with an individual blood transfusion.…”

Heart disease in thalassemia intermedia: a review of the underlying pathophysiology

“…Thromboembolic events were encountered in two large cohorts of thalassemia patients, including both thalassemia major and TI patients, with a frequency of 4.3% και and 5.2%, respectively. 38,39 It must be noted that the prevalence of such events was higher in splenectomized patients than in non-splenectomized ones. In particular, thromboembolic complications were even more frequent in transfusion-independent splenectomised TI patients (29%), compared to regularly transfused TM patients (2%).…”

Non-transfusion-dependent thalassemias

“…[59][60][61] Clinically, the prevalence of thrombotic events in patients with β-thalassemia intermedia can reach up to 20%, compared to less than 1% in patients with β-thalassemia major. 30,[62][63][64] These events are mostly venous and primarily occur in splenectomized patients (22.5% vs. 3.5% prevalence rate in splenectomized vs. non-splenectomized patients; P<0.001). 30,64 Other risk factors for thrombotic events include advancing age, total hemoglobin level less than 9 g/dL, history of thrombotic or other vascular events, elevated platelet (>500x10 9 /L) and nucleated red blood cell counts (>300x10 6 /L), 30,43,64,65 while other conventional risk factors are often absent in such patients.…”