6 Section Editor: Dr. Michael Kroll

Polycythemia

DIFFERENTIAL DIAGNOSIS INVESTIGATIONS SPURIOUS—stress (Geisbo¨ck’s syndrome), BASIC decrease intravascular volume LABS—CBCD, lytes, urea, Cr, LAP, vitamin B12, PRIMARY—polycythemia rubra vera RBC mass (total volume Hct, to rule out SECONDARY wHERAw spurious causes), carboxyhemoglobin level, cor- HYPOXIA—obstructive sleep apnea, COPD, smok- tisol level, peripheral blood smear ing, high altitude IMAGING—CXR EPO-SECRETING TUMORS—renal, hepatoma, cere- SPECIAL bellar, pheochromocytoma JAK2 MUTATION—JAK2 is a cytoplasmic tyrosine RENAL—polycystic kidney disease, hydronephro- kinase activated by EPO binding to its receptor; sis, post-transplant the V617F mutation activates JAK2 and thereby ADRENAL—Cushing’s syndrome drives EPO-independent erythropoiesis EPO LEVEL—low in PRV, high if secondary causes PATHOPHYSIOLOGY HYPOXIA WORKUP—oximetry, ABG, CO-hemoglobin SOLID TUMOR WORKUP—CT abd, MRI head (if DEFINITION OF POLYCYTHEMIA—hematocrit >0.6 tumors) in ?, hematocrit >0.5 in / BONE MARROW BIOPSY—rule out myelofibrosis and CML Related Topics Hypoxemia (p. 92) DIAGNOSTIC ISSUES Myeloproliferative Disorders (p. 165) CRITERIA FOR POLYCYTHEMIA RUBRA VERA (PRV) ABSOLUTE—" RBC mass, no secondary cause (nor- mal PaO2, EPO not elevated) MAJOR—splenomegaly, JAKV617F CLINICAL FEATURES 3 3 MINOR—WBC >1210 /mL, platelet >400 10 /mL, HISTORY—hyperviscosity (headache, blurred vision, LAP >100U/L and vitamin B12 >650pmol/L epistaxis), dyspnea, epigastric pain, weight loss, fever, [>880 pg/mL] night-sweats, pruritus, erythromelalgia, recent travel DIAGNOSIS—need absolute criteria plus one major to high-altitude areas, past medical history (respira- or two minor criteria for the diagnosis of poly- tory diseases, myeloproliferative disorders, myocar- cythemia rubra vera. See myeloproliferative disor- dial infarction, stroke, pulmonary embolism, DVT, ders (p. 165) for more details renal disorders, smoking), medications (androgens, EPO) MANAGEMENT PHYSICAL—hypertension, oxygen saturation, facial TREAT UNDERLYING CAUSE—relative (hydration), plethora, conjunctival injections, engorgement of the CO hemoglobinemia (smoking cessation. See veins of the optic fundus, abdominal mass, hepato- p. 418), sleep apnea (CPAP. See p. 17), polycythe- megaly, splenomegaly, excoriations, stigmata of a mia vera (cytoreduction with hydroxyurea is prefer- prior arterial or venous thrombotic event, gouty able to phlebotomy to keep hematocrit <0.45 in ? arthritis, and tophi and <0.42 in /, ASA 81 mg PO daily prevents thrombosis—but watch out for bleeding)

D. Hui, Approach to Internal Medicine, DOI 10.1007/978-1-4419-6505-9_6, 143 Ó Springer ScienceþBusiness Media, LLC 2006, 2007, 2011 144

Microcytic Anemia NEJM 2005 352:10

DIFFERENTIAL DIAGNOSIS INVESTIGATIONS (CONT’D)

wTAILSw LIVER BIOPSY THALASSEMIA BONE MARROW ASPIRATE AND BIOPSY WITH IRON ANEMIA OF CHRONIC DISEASE—infection, STAIN malignancy, inflammatory disorders IRON DEFICIENCY—blood loss (GI, GU, vaginal, DIAGNOSTIC ISSUES trauma), iron-deficient diet, celiac disease, atrophic IRON INDICES gastritis, renal failure on EPO, pulmonary hemosi- Ferritin Iron TIBC % sat derosis, intravascular hemolysis Iron deficiency ##"# LEAD POISONING Anemia of "/N # N/# N/# SIDEROBLASTIC chronic disease PATHOPHYSIOLOGY Thalassemia "/N "# " DEFINITION OF MICROCYTIC ANEMIA—Hb Sideroblastic N/" N/# N/# N/# <135 g/L [<13.5 g/dL], MCV <80 fL SEQUENCE OF IRON DEFICIENCY—# iron !"TIBC DISTINGUISHING FEATURES BETWEEN IRON !#Hb !#MCV ! hypochromia DEFICIENCY AND THALASSEMIA ANEMIA OF CHRONIC DISEASE—chronic inflamma- RDW—red cells in thalassemia tend to have a tory states such as malignancy, infection and rheu- narrower distribution than in iron deficiency matologic diseases !"INFg, TNFa, I