Polycythemia Rubra Vera

1. Definition
   1. Excessive Red Blood Cell production
2. Epidemiology
   1. Men affected more than women
   2. Median age of onset: 60 years old
   3. Incidence: 2.3 per 100,000 persons per year
3. Pathophysiology
   1. Excessive Red Blood Cell production (erythrocytosis)
   2. Results in increased blood viscosity and blood volume
   3. Ultimately results in thrombosis
4. Causes
   1. Primary Polycythemia
      1. Chronic myeloproliferative disease
   2. Secondary Polycythemia
      1. Tobacco abuse (Smoker's Polycythemia)
      2. Renal Cell Carcinoma
      3. Chronic heart or lung disease
      4. Methemoglobinemia
      5. Living at high altitude
      6. Hydronephrosis
      7. Anabolic Steroid secreting tumor
      8. Erythropoietin secreting tumor
      9. Decreased plasma volume (e.g.. dehydration)
5. Symptoms (thrombotic event on presentation in 20%)
   1. Pruritus after bathing
   2. Cerebral Circulation Impairment
      1. Headache
      2. Tinnitus
      3. Dizziness
      4. Visual disturbance
      5. Transient Ischemic Attack symptoms
      6. Paresthesias
   3. Other associated symptoms
      1. Weight loss
      2. Diaphoresis
      3. Weakness
6. Signs
   1. See complications below
   2. Plethoric facies
   3. Retinal vein engorgement
   4. Cyanosis
   5. Splenomegaly in 75% of patients
7. Labs
   1. Red Blood Cell related increases
      1. Elevated Hemoglobin And Hematocrit
         1. White men: Hemoglobin >18 mg/dl (Hematocrit >52%)
         2. Black men: Hemoglobin >16 mg/dl (Hematocrit >47%)
         3. Women: >16 mg/dl (Hematocrit >47%)
      2. Elevated Red Blood Bell count
         1. See diagnosis below
   2. Proliferation of all cell lines (50% of patients)
      1. Thrombocytosis
      2. Leukocytosis
8. Diagnosis
   1. Exclude secondary causes of increased RBC Count
   2. Criteria
      1. Major Criteria (first two required)
         1. Increased Red Blood Cell mass
            1. Men: >36 ml/kg
            2. Women: >32 ml/kg
         2. Normal arterial Oxygen Saturation (>92%)
         3. Splenomegaly (or two minor criteria below)
      2. Minor Criteria (two required if no Splenomegaly)
         1. Platelet Count >400 x10^3/uL
         2. Leukocyte count >12 x10^3/uL
         3. Alkaline Phosphatase >100 U/L
         4. Serum Vitamin B12 >900 pg/ml
   3. Experimental diagnostic tools
      1. Endogenous erythroid colony growth in EPO-free medium
      2. Bone Marrow Biopsy: Polycythemia-specific finding
      3. Serum Erythropoietin low
         1. Test Sensitivity: 70%
         2. Test Specificity: 90%
9. Complications
   1. Accelerated atherosclerotic and thrombotic disease
      1. Cerebrovascular Accident
      2. Myocardial Infarction
      3. Peripheral Vascular Disease
      4. Other rarely affected vessels
         1. Mesenteric thrombosis
         2. Hepatic vein thrombosis or Portal Vein Thrombosis
   2. Hemorrhage
      1. Epistaxis
      2. Acute GI Bleed
   3. Progression to other hematologic disorder
      1. Myelofibrosis (20% of patients)
      2. Leukemia (5% of patients)
10. Management: Myelosuppression
    1. Goal: Keep Hematocrit below threshold
       1. White men: Hematocrit <45%
       2. Black patients and all women: Hematocrit <42%
    2. Age Under 60 years
       1. Low or intermediate risk patients
          1. Repeated phlebotomy
          2. Interferon alfa-2b
          3. Low dose Aspirin (Platelet Count <150 x10^3/uL)
       2. High risk patients
          1. Low or Intermediate Risk Management options (above)
          2. Hydroxyurea
          3. Bisulfan
    3. High risk patients over age 60 years
       1. Repeated phlebotomy
       2. Low dose Aspirin
       3. Hydroxyurea
       4. Busulfan
    4. Women of child bearing age
       1. Low or intermediate risk patients
          1. Repeated phlebotomy
          2. Low dose Aspirin (Platelet Count <150 x10^3/uL)
       2. High risk patients
          1. Low or Intermediate Risk Management options (above)
          2. Interferon alfa-2b
          3. Bisulfan
11. Management: Pruritus
    1. Antihistamines
    2. Paroxetine
    3. Oatmeal Bath
    4. Interferon alfa-2b
    5. Diehn (2001) Br J Haematol 115:619-21
12. Prognosis: Median survival in symptomatic patients
    1. Survival without treatment: 6-18 months
    2. Survival with treatment: >10 years
13. References
    1. Stuart (2004) Am Fam Physician 69(9):2139-46
    2. Tefferi (2001) Am J Med 109:146
    3. Tefferi (2003) Mayo Clin Proc 78:174-94