A 29-year-old woman comes to the emergency department due to fever and headache for the last week. The patient has a generalized tonic-clonic seizure while being evaluated. Laboratory results are as follows: Peripheral blood smear is shown in the exhibit.
Which of the following is the most likely underlying cause of this patient's current condition?

Question

A 29-year-old woman comes to the emergency department due to fever and headache for the last week.  The patient has a generalized tonic-clonic seizure while being evaluated.  Laboratory results are as follows:  Peripheral blood smear is shown in the exhibit. 
 Which of the following is the most likely underlying cause of this patient's current condition?

Quizplus · Accepted Answer

11ec160b_3998_d03b_9249_dbf84b7683b1_MD0001_00 This patient has the classic pentad of manifestations for acquired thrombotic thrombocytopenic purpura (TTP): Severe thrombocytopenia: Platelet-rich clots form in the microvasculature, leading to rapid platelet consumption. Microangiopathic hemolytic anemia (MAHA): Erythrocytes are mechanically sheared by the microvascular thrombi, leading to intravascular hemolytic anemia. This typically causes an elevated indirect bilirubin level and an undetectable haptoglobin level (haptoglobin binds free hemoglobin in the circulation), but confirmation of MAHA requires identification of schistocytes (eg, triangle cells, helmet cells) on peripheral blood smear. Neurologic manifestations (eg, headache, seizure), renal insufficiency, and fever (the remainder of the pentad) occur in a minority of patients Unlike patients who have disseminated intravascular coagulation (a consumptive coagulopathy also associated with MAHA and thrombocytopenia), those with TTP have normal coagulation studies because coagulation factors are not significantly consumed by the formation of platelet-rich clots (Choice A). TTP is triggered by the formation of autoantibody inhibitors against ADAMTS-13, a protease that cleaves ultralarge von Willebrand factor (VWF) multimers in the circulation, reducing their prothrombotic activity. Patients with TTP have very low levels of ADAMTS-13, which increases the proportion of ultralarge VWF multimers and leads to the aggregation and activation of platelets. Plasma exchange, which removes the autoantibody inhibitors against ADAMTS-13, is generally curative. (Choice C) Expansion of neoplastic myeloid precursors in the bone marrow is seen in acute myeloid leukemia, which can cause anemia and thrombocytopenia due to bone marrow infiltration. However, peripheral blood smear would show leukemic blast cells, not schistocytes. (Choice D) Inherited deficiency of glucose-6-phosphate dehydrogenase typically causes hemolytic anemia during times of oxidative stress (eg, infection, medication exposure, certain foods). High bilirubin and low haptoglobin are often present due to hemolytic anemia; however, thrombocytopenia is not seen, and peripheral smear would show bite cells and Heinz bodies, not schistocytes. (Choice E) A missense mutation at the sixth position of the hemoglobin beta chain is seen in sickle cell anemia, which is marked by periods of acute on chronic hemolytic anemia (eg, elevated bilirubin, low haptoglobin). However, peripheral smear would show sickled erythrocytes, not schistocytes; in addition, thrombocytopenia is not generally seen. Educational objective: Thrombotic thrombocytopenic purpura classically presents with the pentad of severe thrombocytopenia, microangiopathic hemolytic anemia (eg, schistocytes on peripheral smear), renal insufficiency, neurologic symptoms, and fever. However, all these signs and symptoms are rarely present. Diagnosis is often made by identifying severe deficiency of ADAMTS-13, a protease that cleaves large von Willebrand factor multimers off the endothelium.

A 29-Year-Old Woman Comes to the Emergency Department Due to Fever