Haemostatic problems in acute promyelocytic leukaemia.
Despite the development of highly effective treatment strategies for acute promyelocytic leukaemia around 10% of patients die in the presentation period as a consequence of the associated bleeding diathesis. The cause of the coagulopathy is complex resulting from a combination of tissue factor (TF) and cancer procoagulant (CP) induced disseminated intravascular coagulation, exaggerated fibrinolysis due predominantly to enhanced expression of annexin II on APL blast cell membranes and blast cell production of cytokines. All-trans retinoic acid (ATRA) has revolutionised the treatment of APL. When combined with chemotherapy long term survival rates of up to 80% can be achieved. Commencement of ATRA induces APL blast cell differentiation and is associated with a rapid resolution of the bleeding tendency through a combination of effects which include up regulation of thrombomodulin and down regulation of TF and CP production and cell surface expression of annexin II.
Arbuthnot
Carolina
C
Department of Haematology, University Hospital Birmingham NHS Foundation Trust, Edgbaston, Birmingham, UK. carolina.arbuthnot@uhb.nhs.uk
Wilde
Jonathan T
JT
D002454:Cell Differentiation / Q000187:drug effects; D003131:Combined Modality Therapy; D006474:Hemorrhagic Disorders / Q000209:etiology* / Q000503:physiopathology / Q000628:therapy; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000150:complications* / Q000503:physiopathology / Q000628:therapy; D014212:Tretinoin / Q000494:pharmacology / Q000627:therapeutic use
D014212:Tretinoin