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Polycythemia Dr Vaishali Jain MAHSA University College 31 st May 2012. Polycythemia. Abnormally high red cell count, usually with corresponding increase in the hemoglobin level. Polycythemia - types . Polycythemia. Absolute (True). Relative. Increase in total red cell mass - PowerPoint PPT Presentation
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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!