In this week’s Case Record of the Massachusetts General Hospital, a 16-year-old girl with a history of lupus nephritis was seen in the emergency department because of altered mental status. She was somnolent and agitated and had no focal neurologic signs. Brain CT revealed no abnormalities. Laboratory studies revealed anemia and thrombocytopenia.
A diagnosis of thrombotic thrombocytopenic purpura (TTP) should be considered in a patient with fever and changes in mental status who has laboratory findings of microangiopathic hemolytic anemia and thrombocytopenia.
• What is the pathophysiology of TTP?
TTP is due to deficiency of ADAMTS 13, a protease that breaks down large, thrombogenic von Willebrand factor multimers into monomers. In a thrombotic microangiopathy, such as TTP, an insult to the microvasculature leads to microthrombus formation with consumption of platelets, shearing of red cells with hemolysis, and the laboratory findings of schistocytes, thrombocytopenia, and anemia.
• What are additional laboratory features of hemolysis?
Low or undetectable haptoglobin and an elevated reticulocyte count are consistent with a diagnosis of hemolysis.
Table 2. Differential Diagnosis of Thrombotic Microangiopathy.
Morning Report Questions
Q: When should platelets be administered to patients with TTP?
A: Platelet transfusion in patients with TTP may be associated with acute deterioration or even death. For this reason, platelet transfusion is relatively contraindicated in patients with thrombotic thrombocytopenic purpura and should be limited to the treatment of life-threatening bleeding.
Q: What is the treatment of choice for patients with TTP?
A: In patients with idiopathic TTP, microvascular hemostasis is disrupted; plasma exchange is a life-saving procedure for these patients, because it corrects the perturbation by replacing the ADAMTS 13 enzyme and removing, over the course of several procedures, the autoantibody inhibitor that is often detected during the acute illness. Patients with idiopathic TTP used to be treated with plasma infusion or plasma exchange, but a randomized, controlled trial conducted approximately 20 years ago showed the superiority of plasma exchange.