Case-based MCQ

B👍 This patient with an acute ischemic stroke has polycythemia, defined as a hematocrit level >49% in men or >48% in women.  Hematocrit is the main determinant of blood viscosity; therefore, significant elevations in hematocrit can result in cerebral microcirculation sludging and potentially life-threatening ischemic events. Polycythemia is generally classified as follows: Primary polycythemia is largely caused by malignant transformation of erythrocyte progenitor cells, which results in unregulated erythrocyte production (eg, polycythemia vera).  Erythropoietin (EPO), the hormone that stimulates red blood cell production, will be low or absent because elevated red blood cell mass exerts a negative feedback effect on EPO-producing cells in the renal cortex. Secondary polycythemia is typically due to elevated circulating EPO levels.  Most cases are caused by conditions associated with chronic hypoxia (eg, cardiopulmonary disease, obstructive sleep apnea), which stimulates EPO secretion, or by EPO-producing tumors (eg, renal cell carcinoma). This patient’s elevated EPO level indicates secondary polycythemia.  Given the patient’s normal BMI, pulse oximetry, and chest x-ray, chronic hypoxia is unlikely.  Therefore, exploration for an EPO-secreting tumor should be undertaken.  Because the kidney is the primary site of EPO production, renal cell carcinoma, a primary malignant neoplasm of the kidney, is most likely (and may explain her several weeks of generalized weakness); abdominal CT scan is the first test of choice for diagnosis.  CT would also evaluate for hepatocellular carcinoma, which sometimes causes EPO production (although it does not always lead to polycythemia, possibly due to inhibited erythropoiesis). Primary polycythemia, which is associated with low (not high) EPO levels, requires bone marrow aspiration/biopsy with JAK2 mutation testing (to evaluate for polycythemia vera).  Secondary polycythemia does not usually require bone marrow evaluation. Factor V Leiden is an autosomal dominant disease associated with venous thromboembolism (VTE), myocardial infarction, and stroke; it is generally suspected when a patient has a family history of VTE or develops VTE at a young age (<50).  Lupus anticoagulant is an antiphospholipid antibody associated with autoimmune diseases and certain drugs/infections; it can cause VTE, thrombocytopenia, stroke, and fetal loss.  Neither factor V Leiden nor lupus anticoagulant is associated with polycythemia. Polycythemia with high circulating erythropoietin (EPO) levels (secondary polycythemia) is usually due to tumors that produce EPO (eg, renal cell carcinoma) or chronic hypoxia (eg, cardiopulmonary disease, obstructive sleep apnea).  Individuals with secondary polycythemia and no evidence of hypoxia should undergo abdominal CT scan to evaluate for renal cell carcinoma.

A 54-year-old woman is admitted to the hospital with a day of right-sided weakness.  The stroke team was activated, but no intervention was performed due to long length of time since symptom onset.  The patient also notes 6 weeks of headaches and generalized weakness.  She has not had recent fever, shortness of breath, cough, chest pain, palpitations, or syncope.  She has no chronic medical conditions and does not take medications.  The patient smoked a pack of cigarettes daily for 20 years but quit 15 years ago.  She does not use alcohol or illicit drugs.  Temperature is 37.1 C, blood pressure is 160/96 mm Hg, and pulse is 80/min and regular.  Oxygen saturation is 99% on room air.  BMI is 25 kg/m2.  Cardiopulmonary examination shows no abnormalities.  Abdomen is soft and tender; there is no hepatosplenomegaly.  Extremities have no cyanosis, clubbing, or edema.  A right facial droop is present.  Motor strength is 2/5 in right upper extremity, 3/5 in right lower extremity, and 5/5 in left upper and left lower extremities.  Sensation is intact diffusely.  Laboratory results are as follows: Hemoglobin 20.2 g/dL Hematocrit 61% Leukocytes 7,200/mm3 Platelets 180,000/mm3 Creatinine 106 umol/L LDL cholesterol 3.11 mmol/L Erythropoietin level 22.9 mU/mL (normal: 4.1-19.5) MRI of the brain reveals an acute infarction involving the left internal capsule.  Chest x-ray is normal.  ECG shows normal sinus rhythm.  Echocardiogram shows no abnormalities.  Which of the following is most likely to establish a diagnosis in this patient? A. Bone marrow aspiration B. CT scan of the abdomen C. Factor V Leiden mutation testing D. Lupus anticoagulant E. Serologic test for syphilis

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