Pancytopenia

Question 1

What is pancytopenia?

Answer 1

A deficiency of blood cells of all lineages

Question 2

What can cause pancytopenia due to reduced production?

Answer 2

Bone marrow failure - inherited syndromes e.g. Fanconi’s anaemia, acquried (primary and secondary)

Question 3

What are the clinical features of Fanconi’s anaemia?

Answer 3

Short stature, skin pigment abnormalities e.g. cafe au lait patches, radial ray abnormalities, hypogenitalia, endocrinopathies, GI defects, cardiovascular, renal, haematological i.e. multi-system disease

Question 4

When does Fanconi’s anaemia typically present and what is the disease mechanism?

Answer 4

• Median age - 7 years
• Unable to correct inter-strand cross links (DNA damage)
• Macrocytosis followed by thrombocytopenia, then neutropenia
• Bone marrow failure risk - 84% by 20 y/o
• Leukaemia risk - 52% by 40 y/o

Question 5

What are some causes of acquired bone marrow failure?

Answer 5

• Idiopathic aplastic anaemia - autoimmune attack against haemopoietic stem cell
• Myelodyplastic syndrome
• Acute leukaemia

Question 6

What is myelodysplastic syndrome?

Answer 6

• Dysplasia, hypercellular marrow, increased apoptosis of progenitor and mature cells
• Propensity for evolution into AML

Question 7

Why can acute leukaemia cause pancytopenia?

Answer 7

• Proliferation of abnormal cells from leukaemia stem cells
• Failure to differentiate or mature into normal cells
• Prevent normal haemopoietic stem/progenitor development by hijacking/altering the haemopoietic niche and marrow microenvironment

Question 8

What can cause secondary bone marrow failure?

Answer 8

• Drug induced e.g. chemo, chloramphenicol, alcohol - causes aplasia B12/folate deficiency (nuclear maturation can affect all lineages)
• Infiltrative - non-haemopoietic malignant infiltration, lymphoma
• Viral - HIV

Question 9

What can cause pancytopenia due to increased destruction?

Answer 9

Hypersplenism - increased splenic pool, increased destruction that exceeds bone marrow capacity, usually associated with significantly enlarged spleen

Question 10

What can cause hypersplenism?

Answer 10

• Splenic congestion - portal HPT, congestive cardiac failure
• Systemic disease - rheumatoid arthritis
• Haematological diseases - splenic lymphoma

Question 11

What are the clinical features of pancytopenia?

Answer 11

Anaemia + neutropenia + thrombocytopenia

Question 12

What can the clinical features of pancytopenia suggest?

Answer 12

• The lack of circulating blood cells
• The cause of the pancytopenia

Question 13

How is the cause of pancytopenia established?

Answer 13

• History, exam
• FBC, blood film
• Bone marrow exam
• Routine tests - B12/folate, LFTs, virology, autoantibody tests
• Specialised tests - cytogenetics

Question 14

What needle is used for bone marrow trephine biopsy?

Answer 14

Jamshidi needle

Question 15

How does the marrow cellularity vary depending on cause of pancytopenia?

Answer 15

• Hypocellular in aplastic anaemia
• Hypercellular in myelodysplastic syndromes, B12/folate deficiency and hypersplenism

Question 16

What is the supportive treatment for pancytopenia?

Answer 16

• Red cell transfusions, platelet transfusions
• Neutrophil transfusions are NOT routine
• Antibiotic prophylaxis/treatment

Question 17

How is pancytopenia treated due to a primary bone marrow disorder?

Answer 17

• Malignancy - consider chemo
• Congenital - consider bone marrow transplantation
• Idiopathic aplastic anaemia - immunosuppression

Question 18

How is pancytopenia treated due to secondary bone marrow disorder?

Answer 18

• Drug reaction - stop the drug
• Viral - e.g. treat HIV
• Replace B12/folate

Question 19

How is pancytopenia treated due to hypersplenism?

Answer 19

Treat cause if possible, consider splenectomy