Pancytopenia

Question 1

what is it?

Answer 1

deficiency of blood cells of all lineages but generally excludes lymphocytes
Pancytopenia NOT a diagnosis it reflects a diagnosis and does NOT always mean bone marrow failure or malignancy

Question 2

what causes it?

Answer 2

reduced production
- bone marrow failure 
- marrow cellularity 
increased destruction 
-hypersplenism

Question 3

what causes reduced production of cells

Answer 3

bone marrow failure 
-acquired either primary or 2ndry
- inherited syndromes (due to defects in DNA repair/ribosomes/telomeres) 
cancer pre-dispositio 
congenital anomalies 
impaired haemopoiesis 

marrow cellularity

• hypocellular in aplastic anaemia
• hypercellular in myelodysplastic syndromes, B12/folate deficiency, hypersplenism

Question 4

what causes increased destruction of cells?

Answer 4

Hypersplenism
o Increased splenic pool
o Increased destruction that exceeds bone marrow capacity, usually associated with significantly enlarged spleen
o Any cause of splenomegaly can cause hypersplenism although splenic size alone doesn’t always correlate to hypersplenism
- Splenic congestion – portal hypertension
- Systemic diseases – rheumatoid arthritis
- Haematological diseases – splenic lymphoma

Question 5

what causes acquired primary bone marrow failure?

Answer 5

idiopathic aplastic anaemia (autoimmune attack against haemopoietc stem cells)
myleodysplastic syndromes MDS
acute leukaemia (white cell count can be variable)
o Proliferation of ABNORMAL cells (blasts) from leukaemic stem cells (LSC)
o Failure to differentiate or mature into normal cells
o Prevent normal haemopoietic stem/progenitor (HSC) development by ‘hijacking’/altering the haemopoietic niche and marrow microenvironment

Question 6

what causes acquired secondary one marrow failure?

Answer 6

• Drug induced [eg chemotherapy, alcohol, azathioprine, methotrexate chloramphenicol] – causes aplasia
• B12/folate deficiency (nuclear maturation can affect all lineages) (remember hypercellular!)
• Infiltrative- non-haemopoietic malignant infiltration, lymphoma
• Misc.: Viral (eg HIV)/storage diseases

Question 7

how does it present?

Answer 7

•	Anaemia + neutropenia + thrombocytopenia 
•	Anaemia 
o	Fatigue 
o	Shortness of breath
o	Cardiovascular compromise 
•	Neutropenia 
o	Infections – severity and duration 
•	Thrombocytopenia 
o	Bleeding 
- Purpura 
- Petechiae 
- ‘wet’ bleeds including visceral bleeds

Question 8

how is it investigated?

Answer 8

• History, including family history
• Clinical findings
• FBC, Blood film
• Additional routine tests guided by above (B12/folate, LFT’s, virology, autoantibody tests)
• Bone marrow examination
• Specialised tests guided by above (cytogenetics, eg chromosome fragility testing in Fanconi’s syndrome, NGS, WES)

Question 9

what is the supportive management of pancytopenia?

Answer 9

o	Red cell transfusions
o	Platelet transfusions
o	Neutrophil transfusions not routine
o	Antibiotics prophylaxis/treatment
- antibacterials* - treat neutropenic fever promptly based on local unit antibiotic policy without waiting for (microbiology) results 
- antifungals

Question 10

how is primary bone marrow disorder managed?

Answer 10

malignancy - consider chemo
congenital - consider bone marrow transplantation
idiopathic aplastic anaemia - immunosuppression

Question 11

how is secondary bone marrow disorder managed?

Answer 11

drug reaction - STOP
viral - e.g. treat HIV
replace B12/folate

Question 12

how is hypersplenism managed?

Answer 12

• Treat cause if possible

- Consider splenectomy (not appropriate in all cases)