Polycythemia & Polycythemia Vera

1. Approach to polycythemia (defined as Hct >48 in females and >52 in males):

• Physiology of erythropoeisis: EPO is required for differentiation of erythroblasts into reticulocytes
  • 90% of EPO is synthesized by the kidneys, with the primary driver being hypoxia
    • This can be from true hypoxemia (low PaO2), or tissue hypoxia as sensed by the kidney (anemia, decreased O2 release from left-shifting of the Hb-dissociation curve, impaired delivery of O2 from vascular disease)
• Primary polycythemia (characterized by low EPO levels): polycythemia vera, constitutively active EPO receptor
• Secondary (elevated EPO levels):
  • Appropriate: pulmonary disease, right-to-left shunting, OSA, high altitude, hemoglobinopathies (e.g. methemoglobinemia, CO)
  • Inappropriate: renal cell carcinoma, hepatocellular carcinoma, androgen therapy

2.  Overview of polycythemia vera:

• Myeloproliferative neoplasm (clonal proliferation of myeloid cells) characterized by increased red cell mass
• Symptoms: pruritus after warm showers, erythromelalgia (burning pain of extremities characterized by erythema/pallor/cyanosis due to microvascular thromobses) GI complaints (increased risk of PUD from mucosal ischemia, gout
• Diagnosis: primary polycythemia with thrombocytosis/leukocytosis, hypercellular BM, and Janus 2 tyrosine kinase (JAK2) mutation (95-99% sensitive)
• Complications:
  • Increased blood viscosity, with resultant thrombosis (e.g. MI, CVA)
  • Transformation to AML or myelofibrosis
  • Hemorrhage: due to acquired von Willebrand’s disease from platelet binding of vWF
• Treatment:
  • Phlebotomy (goal Hct 42 in females, 45 in males): improved survival compared to myelosuppressive therapy (from lower malignancy risk), at cost of increased thrombosis risk early on
    • As a result of regularly phlebotomy, patients with PV are often iron-deficient, but they should not be started on repletion, as this state helps to further control erythropoiesis
  • Hydroxyurea: decreases thrombosis risk, with possible leukemogenicity
    • Recommended in patients at high risk of thrombosis (age >60, prior thrombosis), with normalization of platelets being treatment goal
  • Low dose ASA: when added to standard therapy of phlebotomy and cytoreduction, results in lower risk of thromobsis compared to placebo (see attached paper)
    • Conversely, high dose aspirin significantly increases the risk of bleeding

3.  Overview of portal vein thrombosis:

• Etiology:
  • Cirrhosis (25%)
  • Hypercoagulable state (particularly myeloproliferative disorder such as PV, PNH)
  • Malignancy
  • Collagen vascular disease: SLE, Bechet’s
  • Inflammatory focus within abdomen: pancreatitis, IBD, abdominal sepsis
  • Pregnancy, OCPs
• Clinical presentation:
  • Acute: typically silent, but can have result in abdominal/back pain and intestinal infarction if severe
    • Unlike in Budd-Chiari syndrome (hepatic vein thrombosis), LFTs should be normal, as the level of the thrombosis is proximal to the liver, and the liver has dual blood supply (hepatic artery)
  • Chronic: results in portal hypertension, with the resultant sequelae (varices, splenomegaly, ascites, pylephlebitis)
• Management (data are scarce, but the following are generally accepted recommendations):
  • Acute: anticoagulation if no contraindication, EGD to rule out varices
  • Chronic: treat consequences of portal hypertension (e.g. shunt, TIPS, splenectomy, variceal banding)
    • The decision to anticoagulate depends on whether the risk of thrombosis is deemed to be greater than the risk of hemorrhage

(Christopher Woo MD, 4/29/11)