Activity levels of natural anticoagulant proteins in childhood acute lymphoblastic leukemia: relation to thromboembolic complications and treatment.

Thromboembolism is a well recognized life-threatening complication in childhood acute lymphoblastic leukemia (ALL). Proper and early diagnosis of thromboembolism is of paramount importance to reduce mortality and morbidity. We evaluated antithrombin III (ATIII), protein C, protein S, and D-dimer in 60 children with ALL compared with 30 healthy controls, and patients were followed up for 12 months for detection of thrombotic complications. The relation between these natural anticoagulants and the development of thrombotic complications, as well as therapy was assessed to identify patients at risk of thromboembolism. ATIII, protein C, and protein S were significantly reduced (P < 0.001) with elevated D-dimer (P < 0.001) in patients with ALL compared with those in the control group. The incidence of thrombotic complications was 16.7%. Patients with thrombotic complications had significantly lower ATIII, protein C, protein S, and platelet count, whereas age, total leukocyte count, and D-dimer were increased compared with those without thrombosis (P < 0.05). Patients under chemotherapy had lower ATIII, protein C, and protein S levels with higher D-dimer compared with the newly diagnosed untreated patients (P < 0.05). ATIII and protein C were positively correlated (r = 0.573, P = 0.002), whereas both were negatively correlated with D-dimer (P < 0.001). ALL is associated with a state of hypercoagulability, which may be attributed to hemostatic derangement because of increased thrombin generation indicated by elevated D-dimer in association with decreased natural anticoagulants ATIII, protein C, and protein S. ALL children during induction/consolidation phase of chemotherapy are at high risk of developing thromboembolism complications and the prophylactic use of anticoagulant should be considered.