Acute Promyelocytic Leukemia Coagulopathy

Acute promyelocytic leukemia (APL) typically presents with a life-threatening hemorrhagic diathesis. New treatment regimens for remission induction including all-trans-retinoic acid (ATRA) or arsenic trioxide (ATO) have significantly improved the mortality due to lethal bleeding, which however remains one of the major barriers to the cure of APL. Simultaneous to bleeding manifestations is often the occurrence of thrombosis, which constitutes an integral part of the thrombo-hemorrhagic syndrome (THS) accompanying the clinical presentation of the disease. The laboratory abnormalities of blood coagulation in these patients are consistent with the diagnosis of disseminated intravascular coagulation (DIC) with excess hyperfibrinolysis. Major determinants of the coagulopathy of APL are endogenous factors expressed by the leukemic cells, including procoagulant factors, fibrinolytic proteins, and non-specific proteolytic enzymes. In addition, these cells have an increased capacity to adhere to the vascular endothelium and secrete inflammatory cytokines, which in turn stimulate the prothrombotic activities of endothelial cells and leukocytes. This chapter will summarize our current knowledge on the epidemiology and pathogenesis of the APL-associated THS and will overview the therapeutic approaches for the management of bleeding and thrombotic complications.