Clinical implications of misdiagnosing thrombotic microangiopathy associated with disseminated malignancy

Background: Thrombotic thrombocytopenic purpura (TTP) is a multisystemic disease consisting of thrombocytopenia, microangiopathic hemolytic anemia, fever, neurologic manifestations and renal dysfunction. It is considered a hematologic emergency for which the treatment of choice is plasma exchange therapy. However, its diagnosis may be frequently missed in the setting of disseminated malignancy. Case Report: Three patients with disseminated malignancy who presented as TTP are discussed. Two of the three patients were given plasma exchange and had fatal outcomes, while the third patient received chemotherapy instead and survived hospitalization. Based on these three patients' clinical presentation, we propose that the following criteria be used for diagnostic consideration of disseminated malignancy-associated TMA: hemolysis; leukoerythroblastic picture on the peripheral blood; coagulopathy(elevated d-dimer, prolonged PT with normal aPTT); LDH levels (> 1000 IU/L); and presence of schistocytes. Conclusions: TMA associated with disseminated malignancy remains a challenging and underdiagnosed condition with very poor prognosis. Plasma exchange has no clinical use and is potentially life-threatening, especially when it delays the administration of the appropriate chemotherapy which is the ultimate treatment for the underlying malignancy that resulted in TMA. Plasmapheresis delivers fresh coagulation factors and may theoretically promote microthrombi formation and leads to worsening of the disease. It is important to be aware of bone marrow metastasis in patients with malignancy and a TTP-like picture. Such patients should be immediately considered for a bone marrow biopsy as chemotherapy should be initiated as soon as possible.