Bleeding and Thrombosis in Acute Lymphoblastic Leukemia

With the advent of modern chemotherapy schedules and the availability of adequate supportive care, the incidence of fatal hemorrhage has dramatically decreased in patients with acute leukemia, but still remains a major cause of death. Acute promyelocytic leukemia (APL) is the subtype where characteristically the highest mortality from bleeding is registered. In a retrospective analysis on 268 consecutive patients with APL collected from multiple institutions in Italy, we found that during remission induction with standard chemotherapy and routine platelet support early hemorrhagic deaths occurred in about 10% of patients, this rate being not significantly different among patients receiving or not heparin or antifibrinolytic agents.' In a study conducted by Kantarajian et al. at M.D. Anderson Hospital the incidence of fatal bleeding seemed related to the severity of thrombocytopenia, high blast and promyelocyte count, anemia, and advanced age, so that APL patients at low (5%) or high (58%) risk of early hemorrhagic death were identified.2 It is likely that death from bleeding will be reduced further with the use of all-trans retinoic acid (ATRA) in the induction phase, as ATRA is reported to rapidly correct the coagulopathy of APL with normalization of fibrinogen levels and disappearance of fibrin/fibrinogen degradation products in 4-8 days.3x4 However, it remains to be demonstrated by appropriate clinical trials whether a correction of laboratory tests is associated with a reduction of early hemorrhagic deaths. In contrast to the body of infor