Though it is well known that DIC can accompany any kind of leukemia, it is most commonly observed in patients with acute promyelocytic leukemia (APL). The development of DIC in leukemia is related to several mechanisms, including release of procoagulant factors, fibrinolytic substances, and inflammatory cytokines, and the interaction of the leukemia cells with the vascular endothelium, macrophages, and platelets.

Tissue factor (TF)32' 33 and cancer procoagulant (CP)34 are expressed in all leukemic cell types, with greatest expression seen in APL. Differentiation of leukemic blasts to more mature forms by all-trans retinoic acid (ATRA) is associated both with loss of expression of CP,35 and with decreased expression of TF,36 regardless of the degree of cellular differentiation.37 Fibrinolytics, such as u-PA and t-PA,3839 and the proteases elastase and chymotrypsin have been identified in leukemic blasts. These enzymes may be responsible for the proteolytic cleavage of clotting factors,40 a2 antiplasmin and fibrinogen.41 In addition, the overexpression of annexin II, a fibrinolytic receptor protein on the surface of APL cells, correlates with both the clinical manifestation of bleeding and the in vitro ability of the promyelocytic cell lines to generate plasmid.42

There is some evidence that induction chemotherapy itself transiently worsens the coagulopathy of APL. Postulated mechanisms for this phenomenon include release of procoagulants from lysis of tumor cells, vascular endothelial damage by chemotherapy, induction of leukemic blast and monocyte tissue factor, and decrease in naturally occurring anticoagulants, such as antithrombin, and protein C and S.43

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