Polycythaemia.pptxPolycythaemia signifies an increase in the number of red blood cells above normal in the circulating blood. The increase may or may not be associated with an elevation in the total quantity of red blood cells in the body.

Polycythaemia signifies an increase in the number of red blood cells above normal in the circulating blood. The increase may or may not be associated with an elevation in the total quantity of red blood cells in the body.
Relative polycythaemia (reduced plasma volume, normal red cell mass).
Dehydration-low fluid intake, vomiting, diarrhoea, sweating, acidosis.
"Stress" polycythaemia.
Absolute polycythaemia (increased red cell mass).
Primary polycythaemia (erythraemia; polycythaemia vera).
Secondary polycythaemia (erythrocytosis

1. Polycythaemia Dr Swetha B P

2. Definition Polycythaemia signifies an increase in the number of red blood cells above normal in the circulating blood. The increase may or may not be associated with an elevation in the total quantity of red blood cells in the body.

3. Classification and Causes Relative polycythaemia (reduced plasma volume, normal red cell mass). Dehydration-low fluid intake, vomiting, diarrhoea , sweating, acidosis. "Stress" polycythaemia . Absolute polycythaemia (increased red cell mass). Primary polycythaemia ( erythraemia ; polycythaemia vera). Secondary polycythaemia (erythrocytosis)--

4. Relative polycythaemia In relative polycythaemia , the concentration of the red cells becomes greater than normal (but total red cell mass is normal) in the circulating blood. This occurs as a result of loss of blood plasma.

5. Absolute polycythaemia In absolute polycythaemia , there is an increase in the total red cell mass. It is of two types: Primary polycythaemia ( erythraemia ; polycythaemia vera; primary proliferative polycythaemia ) denotes absolute polycythaemia of unknown aetiology . This is associated with decreased EPO levels. Secondary polycythaemia (erythrocytosis) denotes absolute polycythaemia of known aetiology (which occurs in response to some known stimulus). This is associated with increased EPO levels.

6. Increased production of EPO as a consequence of central hypoxia High altitude • Cyanotic congenital heart diseases (TOF-tetralogy of Fallot, Eisenmenger's complex) • Pulmonary diseases (e.g. COPD-chronic obstructive pulmonary disease) • Sleep apnoea syndrome • Chronic carbon monoxide poisoning • Smokers • Abnormal haemoglobins with high oxygen affinity

7. Increased production of EPO as a consequence of drugs EPO administration • Androgen administration

8. Increased production of EPO as a consequence of local renal hypoxia Renal artery stenosis • End-stage renal disease • Hydronephrosis • Renal cysts (polycystic kidney disease) • Post-renal transplant erythrocytosis

9. Increased production of EPO or EPO-like substance by tumours Cerebellar haemangioblastoma • Renal tumours (carcinoma, adenoma, sarcoma) • Uterine myoma, hepatocellular carcinoma, phaeochromocytoma

10. Clinical Features The clinical features of polycythaemia include a characteristic "ruddy" cyanosis, dizziness, headache, epistaxis and an increased incidence of thrombotic complications. In addition, clinical manifestations of the underlying disease will be present in secondary forms.

11. Polycythaemia vera Polycythaemia vera is a clonal stem-cell disorder characterised by an increased production of all myeloid elements; however, the disease is generally dominated by an elevated haemoglobin concentration. Haematocrit >60 in males and >56 in females. • Gradual in onset and runs a chronic slowly progressive course. • It is one of the chronic myeloproliferative disorders.

12. Janus Kinases A tyrosine kinase family comprising four members, JAKl , JAK2, JAK3 and TYK2, which are utilised by haematopoietic growth factors and cytokine receptors to phosphorylate tyrosine residues on specific intracellular proteins Located on chromosome 9. JAK2 is used by the EPO and thrombopoietin receptors to transmit signals and thus is integrally involved in haematopoiesis . JAK2 inhibitors are may be useful for managing these patients.

13. Aetiology Unknown; however, hypersensitivity to interleukin-3 may play a role.

14. Clinical Features Predominantly seen in people over the age of 40 and more common in males. • Complaints related to increased viscosity and/or decreased cerebral perfusion include headache, dizziness, vertigo, a sense of fullness in the head, rushing in the ears, visual disturbances, tinnitus, syncope and even chorea. Pruritus, particularly after bathing is frequent and may be disabling. The patients often have a high colour , suffused conjunctivae, deep red palate, dusky red hands and retinal venous engorgement.

15. Clinical Features • Splenomegaly is very common, and symptoms related to it may be present. Hepatomegaly occurs in 30% cases. • Symptoms of peripheral vascular insufficiency, and thrombotic and haemorrhagic complications. • Incidence of peptic ulcer is five times higher in patients with polycythaemia vera. • Bleeding manifestations like epistaxis, bleeding from peptic ulcer, intramuscular haemorrhages and bruising. • Hyperuricaemia may result in the formation of urate stones and uric acid nephropathy.

16. Diagnosis Haemoglobin concentration and haematocrit are markedly elevated. However, in many patients, the plasma volume is also elevated that results in near-normal haematocrit . Hence, it is important to determine the red cell mass. Total white cell count and platelet count are usually elevated. Bone marrow shows either erythroid hyperplasia or panhyperplasia and depletion of iron stores Leucocyte alkaline phosphatase (LAP), serum vitamin B12 levels and B12 binding capacity are increased in majority. Abnormal liver function tests and increased urate levels. Janus kinase 2 (JAK2) mutations (seen in 95% patients with polycythaemia vera, and in 50% cases of essential thrombocytosis and primary myelofibrosis).

17. Diagnostic Criteria Major criteria Haemoglobin > 18.5 g/dl (men) or > 16.5 gldl (women) OR Haemoglobin or haematocrit >99th percentile of reference range for age, sex or altitude of residence 2. Presence of JAK2V617F (a mutation in JAK2) or similar mutation

18. Diagnostic Criteria BM showing hypercellularlity for age and trilineage growth ( panmyelosis ) Subnormal serum EPO level Both major criteria + 1 minor criterion OR first major criterion + 2 minor criteria

19. Complications Thrombotic episodes. • Peptic ulcer. • Hyperuricaemia . • Sudden massive increase in splenic size. • Myelofibrosis and myeloid metaplasia. • Acute leukaemia .

20. TREATMENT It has a very slow course. Aim of therapy is to maintain haematocrit below 45 in males and 42 in females. Repeated venesection (phlebotomy) is the treatment of choice.