A 35-year-old woman comes to the hospital due to sudden-onset numbness in her left arm and face. The patient has had generalized headache, dyspnea on exertion, and easy fatigability for several days but no weakness. She has a history of well-controlled asthma. Temperature is 37.7 C (99.9 F), blood pressure is 110/60 mm Hg, and pulse is 80/min. Light touch sensation is decreased in the left upper extremity and the lower left side of the face. Strength and reflexes are normal. Cardiopulmonary and abdominal examinations are unremarkable. There is no skin rash. Laboratory results are as follows: PT and PTT are normal. Peripheral blood smear shows numerous schistocytes. Urinalysis is positive for mild proteinuria. Which of the following is the most likely underlying cause of this patient's current condition?

Question

A 35-year-old woman comes to the hospital due to sudden-onset numbness in her left arm and face.  The patient has had generalized headache, dyspnea on exertion, and easy fatigability for several days but no weakness.  She has a history of well-controlled asthma.  Temperature is 37.7 C (99.9 F), blood pressure is 110/60 mm Hg, and pulse is 80/min.  Light touch sensation is decreased in the left upper extremity and the lower left side of the face.  Strength and reflexes are normal.  Cardiopulmonary and abdominal examinations are unremarkable.  There is no skin rash.  Laboratory results are as follows:  PT and PTT are normal.  Peripheral blood smear shows numerous schistocytes.  Urinalysis is positive for mild proteinuria.  Which of the following is the most likely underlying cause of this patient's current condition?

Quizplus · Accepted Answer

11ec160b_3998_0ce9_9249_6744764cc243_MD0001_00 This patient's severe thrombocytopenia and schistocytes on peripheral blood smear indicate microangiopathic hemolytic anemia (MAHA). The presence of normal coagulation studies indicate that there is no systemic activation of the coagulation cascade, which makes disseminated intravascular coagulation unlikely (Choice E). Therefore, a platelet-activated thrombotic microangiopathy such as thrombotic thrombocytopenic purpura (TTP) or hemolytic uremic syndrome is most likely. In this case, the patient has 4 of the 5 classic findings of acquired TTP: Severe thrombocytopenia, which may cause bruising or bleeding MAHA, which may cause symptomatic anemia (eg, fatigue, dyspnea on exertion) Renal damage, which may cause renal insufficiency (eg, elevated creatinine) and mild proteinuria Neurologic damage, which may cause confusion, headache, and transient focal findings (eg, numbness, weakness) Fever (not present) Although this pentad of findings is classic, all 5 manifestations are rarely seen. In addition, a purpuric rash (due to subcutaneous bleeding) is sometimes, but not always, present. Acquired TTP occurs due to the formation of an autoantibody inhibitor against ADAMTS-13, a von Willebrand factor (vWF)-cleaving protease. Circulating vWF (produced by megakaryocytes and endothelial cells) normally is released as large vWF multimers that are cleaved to their regular size by ADAMTS-13. These vWF multimers support hemostasis by bridging platelets and subendothelial components to sites of vascular injury. In TTP, the large uncleaved vWF multimers are significantly more prothrombotic and result in diffuse microvascular thrombosis. (Choice A) Henoch-Schönlein purpura (IgA vasculitis) is characterized by IgA immune complex deposition. Typical manifestations include palpable purpura, renal disease, and arthritis/arthralgias. Platelet counts are usually normal. (Choice C) Some features of this patient's presentation could be explained by plasma cell dyscrasias such as multiple myeloma (renal failure, anemia due to bone marrow replacement) and Waldenström macroglobulinemia (neurologic symptoms due to hyperviscosity, autoimmune hemolytic anemia). However, microangiopathic hemolytic anemia would be atypical. (Choice D) A cerebrovascular accident caused by plaque rupture could cause neurologic deficits but would not account for the patient's hematologic and renal abnormalities. Educational objective: Thrombotic thrombocytopenic purpura frequently results from impaired function of the von Willebrand factor (vWF)-cleaving protease ADAMTS-13, which causes the accumulation of uncleaved vWF multimers that are significantly more prothrombotic. Patients develop diffuse microvascular thrombosis, which leads to thrombocytopenia and microangiopathic hemolytic anemia. __________ References: Pathophysiology of thrombotic thrombocytopenic purpura. (http://www.ncbi.nlm.nih.gov/pubmed/20058209) Pathogenesis of thrombotic microangiopathies. (http://www.ncbi.nlm.nih.gov/pubmed/18215115)

A 35-Year-Old Woman Comes to the Hospital Due to Sudden-Onset