Effects of high-dose methotrexate on the hemostatic system in childhood acute lymphoblastic leukemia

Thromboembolic and hemorrhagic complications are significant causes of death in patients with malignancy. These are well-known with the use of certain drugs. This study was planned to investigate whether there was any effect of high-dose methotrexate on the hemostatic system in childhood acute lymphoblastic leukemia.

To evaluate the hemostatic system, we investigated coagulation screening tests (prothrombin time, activated partial thromboplastin time, and fibrinogen), coagulation inhibitors (protein C, protein S, and antithrombin III), and fibrinolytic system (fibrin degradation products and tissue plasminogen activator). These parameters were measured in 35 cycles of high dose-methotrexate (3 g/m(2)) of 20 childhood acute lymphoblastic leukemia cases at baseline and on days 1 and 7 after the therapy.

We found that high-dose methotrexate administration adversely affected both the coagulation system (prolonged prothrombin time and activated partial thromboplastin time and decreased fibrinogen levels) and coagulation inhibitors (decreased protein C, protein S, antithrombin III) on day 1 after chemotherapy compared to the baseline values. The hemostatic parameters began to improve on day 7 after chemotherapy, except for fibrin degradation products. Tissue plasminogen activator levels were not changed with the therapy.

Coagulation cascade (prolonged prothrombin time and activated partial thromboplastin time and decreased fibrinogen) and coagulation inhibitors (decreased protein C, protein S, and antithrombin III levels) have been found to be affected by high-dose methotrexate therapy, but these transient changes did not cause clinical thromboembolic or hemorrhagic complications.