A 72 year old man with esophageal adenocarcinoma presented with five days of progressive exertional dyspnea and a “grabbing” sensation in his chest. He had started FOLFOX two weeks prior to presentation for newly diagnosed metastases.
The patient’s exam was notable only for tachycardia and conjunctival pallor. Laboratory studies revealed a new anemia and thrombocytopenia. EKG had no ischemic changes and serial cardiac biomarkers were normal. CT angiogram of the chest was negative for pulmonary embolism. Further workup demonstrated a hemolytic anemia and the patient’s symptoms improved with blood transfusions. The blood smear showed rare schistocytes and multiple bite cells and a direct Coombs test was negative. The patient required daily blood transfusions, but his renal function and mental status remained unaffected. Plasmapheresis was considered, but an immunologically mediated process was felt to be unlikely.
On his third hospital day, the patient experienced an acute change in mental status. Clinical evaluation suggested a left hemispheric infarct, but tPA was held given thrombocytopenia. A subsequent CT angiogram of the brain was without vessel obstruction. The patient subsequently seized, however, and remained persistently altered. MR of the brain found no metastatic disease or seizure focus. Pulse steroids were administered and plasmapheresis again considered, although not pursued. The patient’s mental status did not recover and his renal function began to decline. After discussion with the patient’s family and oncologist, his goals of care were transitioned towards comfort.
Discussion:
Hemolytic anemia is a common condition encountered by internist and one with a variety of etiologies. When evaluating hemolysis, physicians should always consider the broader and more dangerous thrombotic microangiopathies (TMAs) – particularly thrombotic thrombocytopenic purpura (TTP). This presentation was suggestive of a TMA, which can be subdivided into idiopathic (TTP), drug induced (DI-TMA), or malignancy induced (MI-TMA). Direct interpretation of the blood smear can steer the physician along the appropriate diagnostic path. Our patient’s smear and timing from infusions were less suggestive of an immunologic mediated DI-TMA and TTP was ruled out with negative ADAMTS13. These conditions are unfortunately the only forms of acquired TMA that benefit from plasmapheresis and steroids. The patient was diagnosed with MI-TMA with microthrombotic sequela, and he died three days after stopping supportive care.
Conclusions:
Hemolytic anemia is a common condition with a variety of causes, and is regularly seen on the medicine service. Thrombotic microangiopathy should always be considered in the differential of hemolytic anemia and a blood smear is an essential tool to aid in its diagnosis. Malignancy-induced thrombotic microangiopathy is a rare cause of hemolytic anemia that should be considered in patients suffering from oncologic disease.