Polycythemia vera

Classification, Diagnosis, and Treatment of Polycythemia Vera

1. POLYCYTHEMIA VERA Dr Dilmo Yeldo DNB General Medicine Resident

2. MYELOPROLIFERATIVE NEOPLASMS The Myeloproliferative neoplasms (MPNs) are characterized by a proliferation of myeloid cells in the bone marrow. MPNS are a group of disorders all of which share an origin in a hematopoietic cell; overproduction of one or more of the formed elements of the blood without significant dysplasia ; and a predilection to extramedullary hematopoiesis, myelofibrosis , organomegaly and transformation at varying rates to acute leukemia.

3. CLASSIFICATION

4. POLYCYTHEMIA VERA Polycythemia vera (PV), also called polycythemia rubra vera , is a chronic clonal myeloproliferative disorder characterized by a striking absolute increase in the number of red blood cells and in the total blood volume, and leukocytosis, thrombocytosis, and splenomegaly. The bone marrow is typically hypercellular and exhibits hyperplasia of myeloid, erythroid, and megakaryocyte lineages. PV is most common MPN, occurs in 2.5 per 100,000 persons.

5. CLINICAL FEATURES Isolated thrombocytosis , leukocytosis , or splenomegaly may be the initial presenting manifestation of PV. Uncontrolled erythrocytosis causes hyperviscosity , leading to neurologic symptoms such as vertigo, tinnitus, headache, visual disturbances, and transient ischemic attacks (TIA). Systolic hypertension is also a feature of the red cell mass elevation. Venous or arterial thrombosis may be the presenting manifestation of PV. PV should be suspected in any patient who develops hepatic vein thrombosis.

6. Digital ischemia, easy bruising, epistaxis, acid-peptic disease(due to H. pylori), or gastrointestinal hemorrhage may occur due to vascular stasis or thrombocytosis. Erythromelalgia is a syndrome associated with thrombocytosis, primarily involving the lower extremities and usually manifested by erythema, warmth, and pain of the affected appendage and occasionally digital infarction. It occurs with a variable frequency and is usually responsive to salicylates. Splenomegaly and hepatomegaly can be seen. Skin plethora and conjunctival plethora may be present. A common complaint is aquagenic pruritus , intense itching after exposure to water.

7. DIAGNOSIS

8. CAUSE OF DEATH

9. TREATMENT PHLEBOTOMY Phlebotomy offers prompt and effective reduction of the red cell mass and blood volume to normal values. The goal of phlebotomy is to induce a state of iron deficiency with a normal Hb concentration that will itself suppress erythrocytosis . In most PV patients, once an iron-deficient state is achieved, phlebotomy is usually only required at 3-month intervals. The goal of phlebotomy should be to maintain the hematocrit in the normal range ( 42%-44% for men and 39%-42% for women ). Aspirin is generally given in daily doses of 80 to 100 mg.

10. CYTOREDUCTIVE THERAPY Cytoreductive therapy should be considered in patients at high risk for thrombotic events. The non-alkylating myelosuppressive agent hydroxyurea is the cytoreductive agent of choice in PV at present. The starting dose of hydroxyurea is 500 mg either once or twice daily can rapidly reduce leukocyte, erythrocyte and platelet counts Recombinant human interferon-α is an agent with clear efficacy in PV. Pegylated interferon-α may decrease the expression of JAK2 V617F, suggesting that it induces responses at a molecular level, rather than simply controlling abnormal blood counts.

11. The JAK2 inhibitor Ruxolitinib has been demonstrated to improve symptoms and quality of life in PV patients. The dose Is 10 mg two times daily. Alkylating agents(like Busulfan and Pipobroman ) and radioactive sodium phosphate (32P) are leukemogenic in PV, and their use should be avoided. Imatinib mesylate , a selective tyrosine kinase inhibitor, has been reported to decrease blood counts, splenomegaly, and need for phlebotomy in small series of PV patients. Anagrelide , a phosphodiesterase inhibitor, is a platelet aggregating agent which can reduce the platelet count.

12. Anticoagulants are indicated when a thrombosis has occurred. Generalized pruritus intractable to antihistamines or antidepressants such as doxepin can be a major problem in PV. Splenectomy is useful only as a palliative measure in the late stages of the disease, when the spleen becomes massive and causes early satiety and weight loss, severe anemia, or thrombocytopenia. A role for bone marrow transplantation, either allogeneic or haploidentical , in PV has not been defined.

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