Polycythemia

Dr Vaishali JainMAHSA University College31st May 2012

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

Polycythemia

Polycythemia - types

Polycythemia

Absolute (True) Relative

• Increase in total red cell mass

• Primary (PV) or secondary

• Reduced plasma volume (hemoconcentration)

• Seen in dehydration, stress

Absolute Polycythemia - types

Absolute Polycythemia

Primary Secondary

• Low erythropoietin • High erythropoietin

Primary polycythemia - pathophysiologic classification

• Results from intrinsic abnormality of hematopoetic precursors• Polycythemia vera – we will discuss in detail• Inherited erythropoietin receptor mutations (rare)

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

• Chronic myeloproliferative neoplasm (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

• The mutated forms of JAK2 found in PCV render

hematopoietic cell lines growth factor–independent

Polycythemia vera (PCV)(Polycythemia rubra vera (PRV)/Erythemia/ Primary (Idiopathic) polycythemia)

JAK, Janus kinase STATs, signal transducers and activators of transcription. 

Erythrocyte receptor

Erythrpoietin

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

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

Polycythemia vera, spent phase-Massive splenomegaly

Polycythemia vera

• Non-Hereditary• Age: 50 – 60 years• Common in males

Polycythemia vera – Clinical features

1. 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

2. Thrombosis in cerebrovascular, coronary or peripheral arteries and deep veins of legs (hyper-viscosity & sludging)

3. Spontaneous mucous membrane bleeding (epistaxis and GI

bleeding – due to platelet dysfunction)4. Pruritus (increased by warm bath) 5. Burning pain in extremities (Erythromelalgia) (due to Intravascular

platelet clots)6. Splenomegaly is usual (especially in ‘spent’ phase)

THROMBUS

• 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, eosinophils and monocytes increased• Thrombocytosis; giant platelets• Serum iron: Low level (Increased red cell mass)• Serum Erythropoietin : Low level

Polycythemia vera – hematological findings

Erythrocyte precursors

Polycythaemic stage:• Hyper-cellular marrow with trilineage hyperplasia• Erythroid hyperplasia• Megakaryocytosis – (giant forms, hyperlobulation and

pleomorphism)• Normal reticulin fiber networkSpent phase:• Myelofibrosis• Increased reticulin

Polycythemia vera – bone marrow examination

1. Bleeding - (Disruption of hemostasis) due to increased red cell mass and elevated platelet counts

2. Frequent thrombosis and death3. Terminal acute myeloid leukemia4. Secondary hematologic malignancy: NHL and

Multiple myeloma5. Brain: Infarction and stroke6. Myocardial infarction7. Myelofibrosis and anemia

Polycythemia vera – complications

NB: Secondary gout and splenomegaly are signs of myeloproliferative disorder

MAJOR GOALS OF TREATMENT:1.Reduce high blood viscosity due to increased red cell mass2.Reduce blood volume 3.Prevent hemorrhage and thrombosis and reduce thrombotic

events

No single line of treatment

Polycythemia vera – Principles of treatment

Untreated: SURVIVAL: 6-18 monthsTreated: SURVIVAL: 10 yearsTherapy should be individualised1. Phlebotomy: Lowers PCV (can create iron deficiency)2. Myelo-suppressive drugs: control production of blood cells

in bone marrow e.g. alkylating agents3. Interferon-alpha to reduce risk of transformation to acute

leukemia4. Splenectomy

Polycythemia vera – treatment and prognosis

NB: Post-polycythaemic myelofibrosis and AML respond poorly to therapy

• 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

Imp features necessary for diagnosis of Polycythemia vera

Thank you for your attention!