Polycythemia Dr Vaishali Jain MAHSA University College 31 st May 2012

1. Polycythemia Dr Vaishali Jain MAHSA University College 31st May 2012

2. Polycythemia Abnormally high red cell count, usually with corresponding increase in the hemoglobin level

3. Polycythemia - types Polycythemia Absolute (True) Relative • Increase in total red cell mass • Primary (PV) or secondary • Reduced plasma volume (hemoconcentration) • Seen in dehydration, stress

4. Absolute Polycythemia - types Absolute Polycythemia Primary Secondary • Low erythropoietin • High erythropoietin

6. Primary polycythemia - pathophysiologic classification • Results from intrinsic abnormality of hematopoetic precursors • Polycythemia vera – we will discuss in detail • Inherited erythropoietin receptor mutations (rare)

7. Secondary polycythemia - pathophysiologic classification • A physiologic compensatory response due to tissue hypoxia with increased EPO production • Compensatory: • Heavy smoking (Increased red cell mass) • High altitudes and in athlete • Cyanotic heart disease • Paraneoplastic: • Erythropoietin secreting tumors, e.g. RCC, HCC, Cerebellar hemangioblastoma • Hb mutants with high O2 affinity i.e.hemo-globinopathy

9. Polycythemia vera (PCV) (Polycythemia rubravera (PRV)/Erythemia/ Primary (Idiopathic) polycythemia) • Chronic myeloproliferativeneoplasm (disorder)characterised by trilineage (granulocytic, erythroid, and megakaryocytic) hyperplasia in bone marrow with predominant involvement of erythroid series (erythrocytosis or increased red cell mass) • PCV is strongly associated with activating point mutation in JAK2 • Themutated forms of JAK2 found in PCV render hematopoietic cell lines growth factor–independent

10. Erythrpoietin JAK, Janus kinase STATs, signal transducers and activators of transcription.  Erythrocyte receptor

11. Polycythemia vera • Polycythemia vera is a clonal neoplastic disorder that originates from pluripotent hematopoietic stem cells • Neoplastic clone suppresses normal haemopoietic stem cells as well as erythropoietin production • Erythropoietin production is reduced – abnormal erythroid stem cells require very small amounts of erythropoietin for their differentiation

12. Polycythemia vera – Two phases • Proliferative (Polycythaemic) phase: • Initial phase • Trilineage proliferation with predominance of erythroid cells in bone marrow  increased red cell mass • Spent (post-polycythaemic) phase: • Cytopenias and myelofibrosis • ~5%-Progression to acute myeloid leukemia occurs

13. Polycythemia vera, spent phase-Massive splenomegaly

14. Polycythemia vera • Non-Hereditary • Age: 50 – 60 years • Common in males

15. Polycythemia vera – Clinical features • Hyper viscosity lead to decreased blood flow and dilatation of blood vessels: Headache, vertigo, facial plethora, blurring of vision and congestion of conjunctiva and mucosa • Thrombosis in cerebrovascular, coronary or peripheral arteries and deep veins of legs (hyper-viscosity & sludging) • Spontaneous mucous membrane bleeding (epistaxis and GI bleeding – due to platelet dysfunction) • Pruritus (increased by warm bath) • Burning pain in extremities (Erythromelalgia) (due to Intravascular platelet clots) • Splenomegaly is usual (especially in ‘spent’ phase)

18. THROMBUS

20. Polycythemia vera – hematological findings • Raised hemoglobin: (M> 17.5 g/dl; F> 15.5g/dl ) • Erythrocytosis • Hematocrit (PCV): raised ( M>55% and F>47% ) • Red cell morphology- Initially-normal;with progression to spent phase - anisopoikilocytosis, teardrop cells, and nucleated red cells ; leucoerythroblastic smear • Moderate leukocytosis • Basophils, eosinophilsand monocytes increased • Thrombocytosis; giant platelets • Serum iron: Low level (Increased red cell mass) • Serum Erythropoietin : Low level

23. Erythrocyte precursors

24. Polycythemia vera – bone marrow examination • Polycythaemic stage: • Hyper-cellular marrow with trilineage hyperplasia • Erythroid hyperplasia • Megakaryocytosis – (giant forms, hyperlobulation and pleomorphism) • Normal reticulin fiber network • Spent phase: • Myelofibrosis • Increased reticulin

28. Polycythemia vera – complications Bleeding - (Disruption of hemostasis) due to increased red cell mass and elevated platelet counts Frequent thrombosis and death Terminal acute myeloid leukemia Secondary hematologic malignancy: NHL and Multiple myeloma Brain: Infarction and stroke Myocardial infarction Myelofibrosis and anemia NB: Secondary gout and splenomegaly are signs of myeloproliferative disorder

29. Polycythemia vera – Principles of treatment MAJOR GOALS OF TREATMENT: Reduce high blood viscosity due to increased red cell mass Reduce blood volume Prevent hemorrhage and thrombosis and reduce thrombotic events No single line of treatment

30. Polycythemia vera – treatment and prognosis Untreated: SURVIVAL: 6-18 months Treated: SURVIVAL: 10 years Therapy should be individualised Phlebotomy: Lowers PCV (can create iron deficiency) Myelo-suppressive drugs: control production of blood cells in bone marrow e.g. alkylating agents Interferon-alpha to reduce risk of transformation to acute leukemia Splenectomy NB: Post-polycythaemic myelofibrosis and AML respond poorly to therapy

31. Imp features necessary for diagnosis of Polycythemia vera • Adult patient presenting with bleeding plethora and splenomegaly • Raised haemoglobin and PCV above normal • Exclusion of causes of secondary polycythemia • Erythrocytosis, leucocytosis, and thrombocytosis in blood • Bone marrow showing trilineage proliferation along with prominent hyperplasia of erythroid and megakaryocytic series • Low serum erythropoietin level

32. Thank you for your attention!