title: What's new in the pathogenesis of the coagulopathy in acute promyelocytic leukemia?
abstract: OBJECTIVE
  Acute promyelocytic leukemia (APL) is associated with a complex coagulopathy. In spite of substantial recent improvements in treatment regimens, hemorrhagic death remains the main cause of induction failure. In this review, we delineate recent understanding of the pathophysiology and management of the hemorrhagic diathesis of APL.
  
  
  RESULTS
  Laboratory and clinical data suggest that the malignant leukocytes mediate the hemorrhagic diathesis associated with APL through multiple mechanisms which lead to a combination of consumptive coagulopathy and primary hyperfibrinolysis. Exposure of tissue factor and Annexin II by the leukemic blasts is the main determinants of these processes. Promyelocyte-derived microparticles have recently been implicated in the coagulopathy as well. Total white cell count and platelet count have emerged as good general predictors of hemorrhagic death, along with the different routine hemostatic parameters. Prompt treatment with all-trans retinoic acid, with or without arsenic trioxide, is the most important step in preventing bleeding complications. Repletion of coagulation factors and platelets with blood products remains the mainstay of supportive treatment, whereas the role of recombinant soluble thrombomodulin is currently being investigated.
  
  
  CONCLUSIONS
  The coagulopathy of APL is multifactorial, with both disseminated intravascular coagulation and primary hyperfibrinolysis mediated largely by the malignant leukocytes.
authors.affiliation: Memorial Sloan Kettering Cancer Center, New York, USA.
authors.forename: Simon
authors.initials: S
authors.lastname: Mantha
authors.forename: Martin S
authors.initials: MS
authors.lastname: Tallman
authors.forename: Gerald A
authors.initials: GA
authors.lastname: Soff
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D001777:Blood Coagulation / Q000187:drug effects; D001778:Blood Coagulation Disorders / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy / Q000209:etiology* / Q000401:mortality; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000150:complications* / Q000175:diagnosis / Q000188:drug therapy / Q000401:mortality; D011379:Prognosis; D012074:Remission Induction; D018180:Thrombomodulin / Q000627:therapeutic use; D016896:Treatment Outcome; D014212:Tretinoin / Q000008:administration & dosage
chemical_list: D018180:Thrombomodulin; D014212:Tretinoin