The Role of Thalassaemic Red Cells in the Mechanism Process of Hypercoagulable State in Thalassaemia

Background: Thromboembolic events (TEEs) are recognized complications in thalassaemia, arising from a hypercoagulable state driven by multiple proposed mechanisms. These concerns have prompted numerous investigations to better understand the underlying prothrombotic pathways. This study aimed to compare and correlate the levels of fragmented red blood cells (FRCs), hypercoagulable protein markers, and erythrocyte phosphatidylserine (PS) exposure in thalassaemia patients. This 12-month prospective case-control study at HPUSM recruited 34 thalassaemia patients (21 with thalassaemia major and 13 with thalassaemia intermedia) and 10 healthy controls. Methods: FRCs, erythrocyte PS, protein C, free protein S, and antithrombin III levels were measured. Results: A total of 44 subjects were included, with a mean age of 22.43 ± 10.45 years; most were male (61.4%) and Malay (86.4%). Median FRCs and PS exposure were significantly elevated in both thalassaemia groups compared to controls (p < 0.001 for FRCs; p = 0.048 for PS). Mean protein C and free protein S levels were significantly reduced in thalassaemia major (55.00 ± 10.20% and 65.77 ± 8.66%) and thalassaemia intermedia (61.23 ± 16.99% and 61.11 ± 14.65%) compared to controls (101.60 ± 18.97% and 95.12 ± 23.57%) (p < 0.001 for both), while antithrombin III levels were not significantly different. A significant negative correlation was observed between PS exposure and protein C (p = 0.014). Protein C was positively correlated with free protein S (p = 0.021) and antithrombin III (p < 0.001). Conclusions: Elevated PS exposure and reduced protein C and free protein S levels in thalassaemia patients indicate a potential procoagulant phenotype.