CUTE PROMYELOCYTIC leukemia (APL) is a dis-A tinct variety (French-American-British M3) of acute myelogenous leukemia (AML) distinguished by the presence of a balanced reciprocal translocation between chromosomes 15 and 17,'by the achievement of complete remission (CR) without obligatory marrow and by the association with a potentially life-threatening hemorrhagic diathesis?-6 Although thromboembolic events such as arterial occlusions, pulmonary emboli, hepatic vein occlusion, and portal vein occlusion are very infrequently identified clinically, 7-" postmortem examinations show widespread thrombosis in 15% to 25% of patient^.'".'^ The bleeding diathesis has been attributed to disseminated intravascular coagulation (DIC) resulting from the release of procoagulants from abnormal promyelocyte~'~.'~ accompanying cell senescence and chemotherapy-induced cell lysis. Consequently, heparin has been recommended'8-22 and its use has become a generally accepted practice, although no prospective randomized trial has been conducted to establish the benefits of such an approach. Recently, it has been suggested that heparin may not, in fact, be necessary? Due to the accompanying prolongation of coagulation tests, monitoring the heparin dosage is difficult. Furthermore, the administration of heparin to patients with thrombocytopenia and bleeding may be hazardous. Recent findings give additional support to an old concept that primary fibrinolysis may play a central role in the pathogenesis of the coagulopathy. This has provoked a reassessment of the pathogenesis of the hemostatic disorder as well as the role of heparin. These are important issues because a high incidence of early fatal hemorrhage may contribute to a lower CR rate. 18az4 Yet once CR is achieved, the prognosis compared with other subtypes of AML is relatively good.'~ Z5~ 26 In this report we examine the mechanisms of the bleeding diathesis in patients with APL, review the role of heparin and other strategies in the management of patients with APL, propose a therapeutic approach for patients with APL and coagulopathy, and suggest future directions for studies to address these issues.