Thalassemia major-- on the verge of bleeding or thrombosis?

Thrombotic events have been reported in adult thalassemic patients. To investigate this further, we measured hemostatic parameters in thalassemic children to identify possible predisposing factors in early childhood.

Objective: To assess hemostatic derangements in polytransfused children with beta-thalassemia major (beta-TM).

Methods: Complete blood count, prothrombin time, activated partial thromboplastin time, protein C, protein S, Antithrombin III (AT III), fibrinogen, d-dimer assay, serum iron, serum ferritin and liver function tests were measured in 54 patients and 30 controls using standard lab methods.

Results: Sixteen patients exhibited bleeding manifestations. None of the cases had thromboembolic phenomena. The average pretransfusion haemoglobin in the cases studied was 8.45 +/- 1.6 g/dl, thrombocytopenia was seen in 33.3%, prolongation of prothrombin time was seen in 40.7% and prolongation of aPTT was seen in 46.3%. None of our patients had laboratory features of DIC. Protein C was low in 26.2%, protein S in 28.6% and AT III levels in 46.8% of cases. Mean fibrinogen levels and d-dimers were similar in cases and controls. Serum ferritin levels in the patients were high with a mean of 3,709 +/- 1,625 ng/ml. Serum ferritin had a significant positive correlation with PT (r = 0.382) and ALT (r = 0.315) and a significant negative correlation with protein S (r = - 0.376). Prolonged PT correlated with prolonged aPTT, low protein C, low protein S and serum ferritin levels. Protein C had a significant positive correlation with AT III. Low AT III activity correlated positively with age, aspartate transaminase and alanine transaminase. Average hemoglobin maintained correlated negatively with serum ferritin levels (r = - 0.540), and AST (r = - 0.417). Bleeding episodes correlated with age, liver size and number of transfusions.

Conclusions: Significant alterations in the hemostatic system already exist in polytransfused children with beta-thalassemia that make it a high-risk condition for both hemorrhagic manifestations and future development of thromboembolic events.