Polycythaemia (CH) Flashcards
Define polycythaemia.
Increase in Hb concentration above upper limit of normal for age and sex
What is relative polycythaemia?
Normal red cell mass but low plasma volume
What can cause relative polycythaemia? (3)
- dehydration
- stress
- Gaisbock’s syndrome (younger male smokers with increased vasomotor tone and hypertension)
What is true polycythaemia?
Increased red cell mass
What is polycythaemia vera?
Chronic myeloproliferative neoplasm (haematopoietic stem-cell proliferation) characterised by an erythropoietin-independent, irreversible increase in erythrocyte, granulocyte and platelet counts
Name a condition that is a risk factor for polycythaemia vera?
Budd-Chiari syndrome
What mutation is present in 95% of cases of polycythaemia vera?
JAK2 V617F (but not specific - present in other myeloproliferative neoplasms, AML, CML)
What can polycythaemia vera lead to? (4)
- acute myeloid leukaemia
- myelofibrosis
- thrombosis
- haemorrhage
What cells are increased in polycythaemia?
RBCs, WBCs and platelets
What contributes to hyperviscosity of blood in polycythaemia vera?
Increased RBC mass and/or haematocrit + increased activated WBCs that release pro-inflammatory markers + neutrophil extracellular traps (NETs)
What is secondary polycythaemia?
Driven by excess EPO (appropriately or inappropriately increased)
What causes an appropriate increase in EPO in secondary polycythaemia?
Due to chronic hypoxia:
- chronic lung disease e.g. COPD
- living at high altitude
What are some examples of inappropriate increase in EPO in secondary polycythaemia? (3)
- hepatocellular carcinoma
- renal carcinoma
- EPO abuse by athletes
What is there an increased risk of with elevated blood cell mass in polycythaemia?
Increased risk of thrombosis
(elevated blood cell mass –> hyperviscosity –> slow blood flow and increased thrombosis risk)
What group does polycythaemia usually affect?
Disease of middle and older age
What are the clinical features of polycythaemia? (9)
- headache (fullness in head/neck, dizziness, perspiration)
- fatigue/generalised weakness
- pruritus (worse when skin contacts warm water)
- features of thrombosis (DVT, stroke, angina/MI, PE, PVD)
- night sweats
- bone pains
- erythromelalgia (tenderness/painful burning and/or redness of fingers, palms, heels, toes, face)
- plethora (facial redness)
- splenomegaly
What is the triad of hyperviscosity syndrome seen in polycythaemia?
- mucosal bleeding
- neurological symptoms (dizziness, headaches)
- visual changes
What are some risk factors for polycythaemia? (7)
- age >40
- Budd-Chiari syndrome
- affected family member
- JAK2 mutations
- smoking
- sleep apnoea
- lung diseases
What are the first-line investigations for polycythaemia? (7)
- Hb
- Hct
- WBC
- platelets
- MCV
- LFTs
- JAK2 mutation screen
What happens to Hb in polycythaemia?
Elevated: >165g/L in men, >160g/L in women
What happens to Hct in polycythaemia?
Elevated: >52% in men, >48% in women
What happens to platelet count in polycythaemia?
Elevated due to thrombocytosis
How can we differentiate between polycythaemia vera and secondary polycythaemia?
Decreased serum EPO in polycythaemia vera, but increased in secondary polycythaemia
What is a screen you would do for polycythaemia vera?
JAK2 gene mutation screen
What do investigations show for polycythaemia vera? (5)
- WBC high
- platelets high
- JAK2 mutation present in almost all
- LFTs elevated in Budd-Chiari syndrome –> portal/hepatic vein thrombosis screening
- bone marrow biopsy - prominent erythroid, granulocytic and megakaryocytic proliferation with pleomorphic, mature megakaryocytes
What other features are seen in polycythaemia vera?
Low ESR and raised leukocyte alkaline phosphatase
What are some differential diagnoses for polycythaemia? (2)
- essential thrombocytosis - normal EPO, isolated thrombocytosis absence of elevated Hb/red cell mass
- chronic myelogenous leukaemia - thrombosis much less common, screen for Philadelphia chromosome
How do we diagnose JAK2-positive polycythaemia vera?
High HCt OR raised cell mass
PLUS JAK2 mutation
How do we diagnose JAK2-negative polycythaemia vera?
A1+A2+A3+either another A or two B criteria
(Raised cell mass/Hct + absence of JAK2 mutation + no cause of secondary erythrocytosis + extra/s)
(Low yield)
What are the different forms of management for polycythaemia? (4)
- phlebotomy (venesection) - mechanical reduction in number of RBCs
- antiplatelet prophylaxis (aspirin) - prevent thrombotic events secondary to hyperviscosity
- cytoreductive therapy (hydroxycarbamide/hydroxyurea) - mechanical reduction in RBCs
- JAK2 inhibitors (Ruxolitinib) if everything fails
How do we specifically manage polycythaemia vera?
- low-dose aspirin
- phlebotomy for all patients (remove blood)
- high-risk patients (>65, prior thrombosis) also receive cytoreductive therapy (hydroxycarbamide)
How do we manage secondary polycythaemia?
Treat underlying cause
How do we manage relative polycythaemia? (3)
- fluid repletion
- stop smoking
- reduce use of caffeine-containing beverages, diuretics
What are some complications of polycythaemia? (4)
- thrombosis
- may progress to AML or myelofibrosis
- spent phase disease (increased BM fibrosis, splenomegaly)
- haemorrhage
