The most appropriate diagnostic test to perform at this time is a peripheral blood smear. This patient likely has thrombotic thrombocytopenic purpura (TTP). TTP should be suspected in patients who have microangiopathic hemolytic anemia, characterized by schistocytes on the peripheral blood smear and increased serum lactate dehydrogenase levels, and thrombocytopenia. A peripheral blood smear is essential to determine whether the anemia is caused by a microangiopathic hemolytic process as indicated by the presence of schistocytes. Patients may also have fever; kidney manifestations such as hematuria, elevated creatinine level, and proteinuria; and fluctuating neurologic manifestations, but the absence of these symptoms does not exclude the diagnosis.

Assays for ADAMTS-13 activity and inhibitor titer are available but are best used for prognosis rather than to guide therapy, because TTP requires immediate treatment that cannot be delayed until laboratory test results are available. Low activity levels and a positive inhibitor titer confer a higher risk for relapse.

An osmotic fragility test is used to evaluate for hereditary spherocytosis, which can produce hemolysis in the setting of an acute infection. However, hereditary spherocytosis does not cause thrombocytopenia, kidney injury, or mental status changes.

TTP can overlap with hemolytic uremic syndrome (HUS), which usually occurs in children. HUS may be precipitated by an infectious diarrheal illness, especially Escherichia coli O157:H7 or Shigella species. These bacteria elaborate a toxin that resembles antigens on renal endothelial cells and bind and cause renal cell death. It is not clinically helpful to attempt to distinguish between TTP and HUS, because many patients with HUS respond to plasma exchange, the treatment for TTP.