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)
- 90% of EPO is synthesized by the kidneys, with the primary driver being hypoxia
- 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
- 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
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)
- Acute: typically silent, but can have result in abdominal/back pain and intestinal infarction if severe
- 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)