Coagulopathy

Coagulopathy is most commonly associated with APL, which is characterized by the cytogenetic abnormality t(15;17) or varient. Although APL is the most curable subtype of AML in adults, it needs to be recognized and treated immediately because of the risks of significant bleeding.65 Patients with coagulopathy should be transfused to keep their platelets above 50,000/mm3 and transfused with cryoprecipitate to keep their fibrinogen within the lower limits of normal. Fresh frozen plasma should be used to correct an abnormal prothrombin time or partial thromboplastin time. Heparin and antifibrinolytics, such as amicar, do not have a standard role in the treatment of APL-induced coagulopathy, as trials have demonstrated a similar rate of hemorrhagic death in patients with APL treated with heparin, antifibrinolytics, or supportive care.6667 Initially, it was thought that the coagulopathy in APL was secondary to release of granules from the leukemic promyelocytes.36,68,69 However, it is more likely that the coagulopathy is secondary to release of plasmino-gen activator from leukemic cells; while there is no increase in platelet turnover, there is an increase in fib-rinogen turnover and an increase in fibrin/fibrinogen degradation products with a decrease in a2-antiplas-min levels, suggesting activation of plasmin.3670-74 Recent data suggest that annexin II, a receptor for fib-rinolytic proteins, is increased in patients with APL.75

High levels of annexin increase the production of plas-min.75 All-irans-retinoic acid (ATRA) should be initiated concurrent with chemotherapy in patients with APL. ATRA induces differentiation of leukemic cells into mature granulocytes and decreases the incidence of coagulation and bleeding.76 In addition, ATRA blocks annexin II messenger RNA production through a transcriptional mechanism.75 Patients with the microgranular variant of APL tend to present with hyperleukocytosis in addition to coagulopathy.77 Coagulopathy can also occur in the other subtypes of AML, especially the monocytic forms and patients with high white blood cell counts.36

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