Bleeding and thrombosis in acute leukemia: what does the future of therapy look like?

Abstract

Bleeding and thrombosis are major risk factors for early death in patients with acute leukemia; chemotherapy increases the likelihood of both of these complications. Patients with acute leukemia often present with a hypercoagulable state or with evidence for chronic disseminated intravascular coagulation, even in the absence of active thrombosis and/or bleeding. Leukemic cell procoagulant properties, cytotoxic therapies, and concomitant infections are major determinants of clotting activation in acute leukemia. Clinical manifestations range from localized venous or arterial thrombosis to diffuse life-threatening bleeding. All-trans retinoic acid has greatly improved the management of acute promyelocytic leukemia, but has not significantly changed the rate of early hemorrhagic deaths and may actually promote thrombosis. Randomized, controlled trials of different prophylactic regimens to prevent thrombosis and/or bleeding in acute leukemia are urgently needed, particularly in patients with acute promyelocytic leukemia. Anticoagulant therapy is a unique challenge in patients with acute leukemia, who are at high risk for hemorrhage. Although no guidelines are available for prophylaxis or treatment of thrombosis, extrapolation can be made from existing guidelines for management of patients with other malignancies prolonged periods of treatment-induced thrombocytopenia in patients with acute leukemia, however, require a more judicious application of standard anticoagulant approaches. Use of the newer anticoagulants will require careful assessment of hemorrhagic risk in this group of high risk patients but may be justified under special circumstances.