A 45-year-old woman comes to the physician with headache, trouble concentrating, and fatigue. She is a clerk at a high-end retail clothing store. She has had a mild, generalized headache for a week and finds it difficult to concentrate and maintain focus at work. The patient has also had progressive fatigue that is making it difficult to work and carry out daily activities. She has had heavy menses and taken iron supplements in the past. Two months ago, she got a sunburn on her face and arms while on vacation in Florida. The patient drinks 2-3 alcoholic beverages a week and has a 10-pack-year smoking history. She takes no prescribed or over-the-counter medications.
Her temperature is 36.7 C (98 F), blood pressure is 136/84 mm Hg, pulse is 90/min, and respirations are 16/min. She does not appear to be in acute distress. Her neck is supple. Cardiac, pulmonary, abdominal, and neurologic examinations are all within normal limits.
Laboratory results are as follows:

Direct Coombs test is negative and a blood smear shows hypochromic cells, few reticulocytes, and schistocytes.
Which of the following is the best next step in management of this patient?

Question

A 45-year-old woman comes to the physician with headache, trouble concentrating, and fatigue.  She is a clerk at a high-end retail clothing store.  She has had a mild, generalized headache for a week and finds it difficult to concentrate and maintain focus at work.  The patient has also had progressive fatigue that is making it difficult to work and carry out daily activities.  She has had heavy menses and taken iron supplements in the past.  Two months ago, she got a sunburn on her face and arms while on vacation in Florida.  The patient drinks 2-3 alcoholic beverages a week and has a 10-pack-year smoking history.  She takes no prescribed or over-the-counter medications.
Her temperature is 36.7 C (98 F), blood pressure is 136/84 mm Hg, pulse is 90/min, and respirations are 16/min.  She does not appear to be in acute distress.  Her neck is supple.  Cardiac, pulmonary, abdominal, and neurologic examinations are all within normal limits.
Laboratory results are as follows:

Direct Coombs test is negative and a blood smear shows hypochromic cells, few reticulocytes, and schistocytes.
Which of the following is the best next step in management of this patient?

Quizplus · Accepted Answer

11ec193a_9820_8bc3_853d_0ff1c5fe0fce_MD0002_00 Thrombotic thrombocytopenic purpura (TTP) is likely in this patient with microangiopathic hemolytic anemia (MAHA), thrombocytopenia, and possible neurologic symptoms. The table summarizes the differences between the clinical features of TTP, the closely related hemolytic-uremic syndrome (HUS), and idiopathic thrombocytopenic purpura (ITP). HUS usually has more renal involvement; TTP usually causes more neurologic symptoms. Idiopathic TTP is due to an antibody directed against ADAMTS13, a von Willebrand factor (vWF)-cleaving protease. Reduced ADAMTS13 activity results in large vWF multimers, which stimulate platelet aggregation and lead to the formation of platelet-rich thrombi in the small vessels of multiple organs. It is rare for a patient with TTP to have the full classic pentad (fever, MAHA, thrombocytopenia, renal failure, and neurologic symptoms). The presence of MAHA and thrombocytopenia (not due to other causes) is enough to diagnose suspected TTP and initiate treatment with plasma exchange (even without fever, as in this patient). Measurement of ADAMTS13 activity is not required to make the diagnosis. Replacement of ADAMTS13 via plasma exchange stabilizes and improves most cases of idiopathic TTP. Failure to institute timely therapy can lead to devastating end-organ consequences. Initiating plasma exchange therapy while waiting for additional test results is the most appropriate next step in management. Patients refractory to plasma exchange therapy may respond to rituximab or cyclosporine. (Choice A) Although this patient's recent sunburn may suggest a photosensitivity rash and possible autoimmune disease, her thrombocytopenia and MAHA are more consistent with TTP. Patients with connective tissue disease tend to have arthralgias, fever, and other systemic symptoms not seen in this patient. (Choice B) Antiphospholipid antibody syndrome can cause widespread microvascular and macrovascular thrombosis, but the partial thromboplastin time is prolonged in this disorder (and is only slightly elevated in this patient). (Choice C) Bone marrow biopsy is indicated for the evaluation of systemic malignancy with bone marrow involvement, which can sometimes mimic the findings seen in suspected TTP. Bone marrow biopsy is appropriate if the patient fails to respond to initial plasma exchange therapy. (Choice D) Corticosteroids and other immunosuppressive drugs may reduce antibody formation in idiopathic TTP or prevent bleeding when the platelet count is very low. These are usually given as an adjunct to plasma exchange or later in the course of the disease pending initial response to plasma exchange. Educational objective: Microangiopathic hemolytic anemia and thrombocytopenia suggest the possibility of thrombotic thrombocytopenic purpura (TTP). It is rare to see the full classic pentad. The idiopathic form of TTP is due to an antibody directed against a von Willebrand factor-cleaving protease (ADAMTS13) and is a medical emergency requiring prompt treatment with plasma exchange to replace the protease and prevent end-organ damage. Measurement of low ADAMTS13 activity is not required to make the diagnosis. __________ References: Advances in the pathogenesis, diagnosis and treatment of thrombotic thrombocytopenic purpura. (http://www.ncbi.nlm.nih.gov/pubmed/12660343) How I treat patients with thrombotic thrombocytopenic purpura: 2010. (http://www.ncbi.nlm.nih.gov/pubmed/20686117)

A 45-Year-Old Woman Comes to the Physician with Headache, Trouble