3. When should I be worried?
• When the haemoglobin level is at 18.5g/dL in
men or 17g/dL in women it MAY be abnormal.
• Hct levels >60% in men and >55% in women is
almost INVARIABLY associated with an
increased cell mass.
4. Pathophysiologic Classification
RELATIVE
Reduced plasma volume (hemoconcentration)
ABSOLUTE
Primary (Erythropoietin normal or low)
Polycythemia vera
Inherited erythropoietin receptor mutations
Secondary (High erythropoietin)
Compensatory
Lung disease
High-altitude living
Cyanotic heart disease
Paraneoplastic
Erthropoietin secreting tumors
Haemoglobin mutants with high O2 affinity
Inherited defects that stabilize HIF-α
Chuvash Polycythemia (homozygous VHL mutations)
Prolyl hydroxylase mutations
5. • Historic features:
– Smoking history,
– living at a high altitude,
– congenital heard disease,
– peptic ulcer disease(?),
– sleep apnea,
– chronic lung disease,
– renal disease.
7. POLYCYTHEMIA VERA
• “A myeloproliferative disease arising from a
clonal HSC and resulting in uncontrolled
division of RBC’s.”
• Granulocytes and platelets ↑sed
8. Clinical Features
• Most symptoms are related to an increased red
cell mass and elevated haematocrit
• Hyperviscocity hence there is sluggish blood flow
which mainly affects the _______ system?
• Organomegaly.
• Increased risk of bleeding and thrombotic
disorders.
– MI, DVT, Stroke, BCS, Bowel infarct
– Epistaxis, Bleeding gums. Life threatening(5-10%)
• Plethoric and cyanotic.
• Intense pruritis and Peptic Ulceration(?)
• Symptomatic gout(5-10%)?
9. • Bone Marrow:
– Hypercellular.
– ↑sed red cell progenitors(Mild), also granulocyte
precursors and megakaryocytes.
– Extensive marrow fibrosis(Later stages) Displacement
of HC’s Extramedullary Haematopoiesis.
• Peripheral Smear:
– Hb: 14-28 g/dL; Increase in absolute red cell mas Cr
labelling method
– Hct: >60%
– Iron deficiency?!
– Microcytic erthrocytosis?
– TLC: 12,000 – 50,000 cells/. ↑sed Basophils(?)
– Platelets: >5,00,000/mm3 (Giant forms, qualitatively
poor)
10. MOLECULAR PATHOGENESIS
1. JAK 2: ?(97%)
2. Important kinase for EPO and Thrombopoietin
3. Obligate chaperone for the EPO and TPO receptor
4. After binding autophosphorylation, receptor
phosphorylation and phosphorylation of proteins
involved in cell differentiation, proliferation and
resistance to apoptosis.
5. What if there was no JAK2?
6. Constitutive activation?
7. AML clones don’t have JAK2 mutations?
11. • Without treatment: Death within months of
diagnosis from bleeding or thrombosis.
• Treatment:
– Periodic Phlebotomies
– Anagralide(Hydroxyurea?)
– INF-α
12. Gaisbock syndrome (Spurious polycythemia or
stress polycythemia):
1.Seen in middle aged persons, overweight,
hypertensive chronic smokers
2.Due to a combination of plasma volume
depletion and increased red cell production.
3.Nicotine?
4.Carbon Monoxide?
