Thrombophilia assessment with thrombin generation assay at diagnosis and during induction therapy in children with...

Thrombosis is a significant complication of childhood acute lymphoblastic leukemia (ALL) associated with both the disease itself and its treatment. This study aimed to predict the thrombotic process with TGA performed at diagnosis and during induction therapy in pediatric ALL cases, to assess the contribution of hereditary risk factors, ALL, and treatment to thrombophilia, and to compare the thrombosis tendency according to ALL risk group. The study included 24 ALL patients and 23 healthy children. TGA was performed before the start of induction chemotherapy (ALL BFM-2009 protocol) and on days 8, 15, and 33 of treatment for ALL patients and once for healthy controls. TGA was conducted using a Thrombinoscope (Calibrated Automated Thrombogram; Maastricht, Netherlands) device and kits from the same company. We found the frequency of thrombosis to be 12.5% in children with ALL. Although the number of thrombosis was small (n = 3), the association of peak thrombin and ETP with thrombosis was encouraging: patients who developed thrombosis had higher mean ETP and peak thrombin values on days 8 and 15 of induction therapy compared to patients without thrombosis, with TGA profiles more comparable to those of the healthy control group. Patients' lag time and time to peak thrombin on days 8, 15, and 33 of induction therapy were significantly longer, in addition peak thrombin and ETP values were significantly lower compared to the control group. The results of this study indicate that changes in hemostatic balance did not cause an increase in the thrombin generation potential, and thrombin generation remained low compared to the healthy control group. Although these findings seem to contradict those of studies showing thrombophilia in ALL patients, our study does not support hypercoagulability alone. Considering the absence of signs of hypercoagulability, thrombophilia in these patients may be secondary to endothelial damage caused by the disease and cytotoxic therapy. Comprehensive studies are needed to elucidate the etiology of thrombosis in ALL.