I. Polycythemia

  1. Classification
    1. "Relative" polycythemia = increases in measures of RBC mass (Hb, HCT, RBC count) due to isolated decreases in plasma volume
    2. "Absolute" polycythemia = increases in same from actual increase in RBC mass
      1. Primary polycythemia: Caused by a mutation within RBC progenitors; includes polycythemia vera (see below) and other rarer syndromes
      2. Secondary polycythemia: Caused by excess levels of a stimulator of erythropoiesis, usually erythropoietin (see causes below)
  2. Etiologies of secondary polycythemia
    1. Epo-secreting tumors (e,g, renal cell Ca, hepatocellular Ca, hemangioblastoma, pheochromocytoma, uterine fibroids)
    2. Epo-secreting non-neoplastic lesions (renal cysts, hydronephrosis)
    3. Transplanted kidneys secreting excess Epo (rare)
    4. Use of exogenous Epo
    5. Chronic hypoxemia due to any cause (keep in mind Obstructive Sleep Apnea)
    6. Renal artery stenosis
    7. Hemoglobinopathies that impair O2 release from Hb
    8. Androgens/anabolic steroids
    9. Carbon monoxide exposure

II. Polycythemia vera

  1. Definitions and pathophysiology
    1. A myeloproliferative disorder characterized by consistently elevated RBC counts
    2. Diagnostic criteria--All 3 major criteria or the first 2 major criteria + any two minor criteria (Am. J. Med. 109:141, 2000--AFP):
      1. Major criteria
        1. RBC mass > 36mL/kg for men or > 32mL/kg for women
        2. SaO2 > 92%
        3. Splenomegaly
      2. Minor criteria
        1. Platelet count > 400,000/uL
        2. WBC count > 12,000/uL
        3. Serum alkaline phosphatase > 100U/L
        4. Serum B12 level > 900pg/mL
        5. Unbound B12 binding capacity > 2,200pg/mL
    3. Associated with risk of abnormal thrombosis (unclear if risk correlates with degree of polycythemia) and, more rarely, hemorrhage
  2. Clinical presentation
    1. Thrombotic events
    2. Hemorrhage
    3. Headache
    4. Transient neurologic or ocular sx
    5. Paresthesias
    6. Pruritis after bathing
  3. Treatment
    1. Phlebotomy
    2. Hydroxyurea
    3. 518 pts w/polycythemia vera (90% with no prior h/o thombotic event) randomized to ASA 100mg QD vs. placebo; over mean 3y f/u, incidence of (MI, CVA, PE, major venous thrombosis, or CV death) was sig. less in ASA group (3% vs. 8%); no sig. diff. in major bleeding between the groups (NEJM 350:114, 2004--JW)