Correct!
5. 2 and 4

ATRA acts as a differentiation agent, distinct from chemotherapy, and not associated with myelosuppression or other toxicities typical of chemotherapy agents. However, up to 20% of patients receiving ATRA develop “differentiation syndrome” early in the course of treatment.  This is caused by rapid synchronous maturation of promyelocytes into neutrophils, leading to hypercytokinemia and endothelial injury. Differentiation syndrome is characterized by fever, hypotension, anasarca, acute renal failure, and interstitial pulmonary infiltrates (17).  The diagnosis is made clinically, and treated emergently with corticosteroids. ATRA and other differentiation agents such as ATO may be continued in patients with differentiation syndrome who rapidly improve with corticosteroids. 


Some final thoughts about the diagnosis of APL in our patient. The WBCC in APL may be low, normal or high, and the peripheral smear is typically dominated by promyelocytes and myelocytes rather than blasts. These features may delay identification of APL by automated or manual examination of the peripheral blood smear. In our patient, the paucity of Auer rods (c/w hypo-granular variant APL) further obscured the lineage of the “unclassified white blood cells” identified on his admission CBC differential. When leukemia is suspected, flow cytometry will rapidly make the diagnosis. We hypothesize that our patient experienced early non-specific symptoms of DIC prompting his initial hospitalization three weeks prior to the onset of intracranial hemorrhage, at which time an elevated D-dimer was the only associated abnormal lab value.


APL is a rare but important cause of otherwise unexplained DIC. The inherent limitations of automated CBC differentials can delay diagnosis. When APL-associated DIC is reasonably suspected based on clinical and preliminary laboratory data, intensive transfusion therapy plus ATRA can be life-saving, if the patient has not already experienced a non-survivable complication. 

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