A new study suggests that pediatric patients with beta-thalassemia major (BTM) may be at risk of both bleeding and thrombosis due to a derangement of hemostatic parameters that can exist apart from hepatic iron overload, and also that there may be a balance between these risks in patients at an early age. Details and findings of the study were reported in the journal Cureus.
In this study, researchers based at King Georges Medical University in Lucknow, India, investigated hemostatic parameters associated with bleeding and thrombosis in children with BTM. Included patients had no family histories of bleeding or thromboembolic events. Evaluated parameters included prothrombin time, activated partial thromboplastin time, platelet aggregation, liver function tests, iron profiles, and tests of proteins C and S. Results for patients with BTM were compared with those of age- and sex-matched control individuals.
A total of 54 pediatric patients with BTM were evaluated, and they had a median age of 12 months (range, 4-144). Among patients with BTM, 44 were males, and 10 were females. None of the patients had undergone splenectomy, and all required blood transfusions, with a mean of 5.26 + 4.86 transfusions per patient. A total of 15 control individuals were included in the analysis.
The mean prothrombin time was significantly higher for patients with BTM (14.6 + 1.24 seconds) than for the control group (13.93 + 0.59 seconds; P =.016). The mean activated partial thromboplastin time was also significantly elevated for patients with BTM (36.41 + 7.42 seconds) compared with that of control individuals (27.33 + 2.94 seconds; P <.001).
The patients with BTM showed significantly lower mean protein C and protein S activity than control individuals did (P <.001 for each). Patients with BTM also showed a greater mean aggregability of platelets induced by adenosine 5-disphosphate than the control group did (P =.007).
Patients with BTM had slightly deranged liver function, with elevated mean total serum bilirubin, mean serum aspartate transferase, and mean serum alkaline phosphatase. There also was an elevation in mean serum ferritin in patients with BTM (815.38 + 789.73 ng/mL), in addition to a slightly elevated mean serum iron (140.62 + 42.57 mg/dL) and slightly reduced mean serum total iron-binding capacity (229.20 + 32.64 mg/dL).
The researchers noted that a relationship between serum ferritin and hepatic dysfunction from iron overload is generally not seen until serum ferritin reaches a threshold of 2000 ng/mL. This was a threshold reached by a small percentage (5.5%) of patients with BTM in this study of young children with limited transfusion histories.
“Deranged hemostatic parameters can exist in otherwise healthy children with BTM right from infancy and this may not be solely contributed by hepatic dysfunction or multiple blood transfusions,” the researchers wrote in their report. “In children with BTM, a state of balance exists between bleeding and thrombosis in vivo despite the presence of deranged hemostatic parameters and an imbalance may lead to either bleeding or thrombosis at a later age,” they concluded.
Reference
Singh S, Yadava G, Kushwaha R, et al. Bleeding versus thrombotic tendency in young children with beta-thalassemia major. Cureus. 2021;13(12):e20192. doi:10.7759/cureus.20192