Cause:A clonal myeloproliferative disease; most due to a dominant "gain-of-function" mutation of JAK2 gene on short arm of chromosome 9, which may manifest as P. vera, thrombocythemia, or myelofibrosis (Nejm 2006;355:2452; 2005;352:1779)

Pathophys:Excessive production of rbcs causes elevated crit, sludging at crits >60% only (Nejm 1970;283:183); increased cellular breakdown causing gout; venous distention and headache; increased atherosclerosis, unclear why

Male > female. Incidence = 3/10 000/5 yr, while that of benign idiopathic polycythemia = 51/10 000K/5 yr (Ann IM 2003;139:470)

Sx:Headache, dizziness, warm bath-induced pruritus (Nejm 1972;286:845)

Si:Splenomegaly (75%), hepatomegaly, red sclerae (r/o conjunctivitis), plethora

3% annual mortality, 3.5%/yr incidence of thrombotic events (Ann IM 1995;123:656)

Gout; thromboembolic diseases; erythromelalgia (Thrombocythemia); Budd-Chiari due to hepatic venous occlusion even in occult myeloproliferative disease, ie, may be 1st sx esp in young female (Ann IM 1985;103:329)

r/o other etiologies of high crit:

• Hypovolemia: pheochromocytoma, Addison's, stress
• Increased erythropoietin causes (can rx all by adenosine receptor inhibition of erythropoietin effect by theophylline—Nejm 1990;323:86):
• Hgb abnormalities with increased O₂ affinity, eg, Hgb Rainier, Chesapeake, Kempsey, Yakima, M.
• Hypoxia due to lung disease, etc = 95% of polycythemics; in smokers esp (Nejm 1978;298:6)
• Tumor-producing erythropoietin, eg, of posterior fossa of brain, hepatoma, renal, uterine fibroid
• Renal transplant

Lab:

Hem:

• White count increased to 30 000 with increased or normal leukocyte alkaline phosphatase (LAP) activity
• B₁₂ high due to increased binding protein in all myeloproliferative diseases and some leukemoid reactions (Ann IM 1971;765:809)
• Platelets elevated (80%)
• Basophils, elevated >40/mm³ is diagnostic of myeloproliferative disease, though some false negs (Clem Finch, 1972)
• JAK2 gene mutation; if present, rules out benign reactive erythrocytosis
• Erythropoietin levels; low to normal = 3-5 U/d in 24-h urine; elevate to 30 U/d in anemia or secondary polycythemia; useful in 2nd stage w/u of polycythemia (Nejm 1986;315:283)
• Plasma volume increased in 60% of P. vera (decreased in stress polycythemia)
• Rbc volume increased in P. vera and secondary causes, normal in stress polycythemia
• Hgb electrophoresis or blood gases at 37°C (graph—Ann IM 1976;84:518) to r/o abnormal Hgb
• Carboxy Hgb level to r/o smoking cause (Nejm 1978;298:6)
• Marrow shows larger megakaryocytes, unlike CML and secondary causes of elevated platelets (Finch); erythroid hyperplasia; no fat; no Fe