Pancytopenia

Question 1

What is pancytopenia?

Answer 1

A deficiency in blood cells of all lineages (RBC, platelets, neutrophils)
Generally excludes lymphocytes

Question 2

Pancytopenia is caused by reduced production or increased destruction of cells. True/False?

Answer 2

True

Question 3

List causes of reduced production of all blood cells

Answer 3

BONE MARROW FAILURE
Inherited
Acquired (primary)
Acquired (secondary)

Question 4

Fanconi’s anaemia is an inherited marrow failure syndrome. What is the defect?

Answer 4

Failure to repair DNA damage

Question 5

When is Fanconi’s anaemia usually diagnosed?

Answer 5

Childhood

Question 6

List clinical signs of Fanconi’s anaemia

Answer 6

Short stature
Skin pigment abnormality (Cafe au Lait patches)
Hypogenitalia
Endocrinopathies
Organ defects (GI, cardiac, renal)
Skeletal deformities

Question 7

What haematological abnormalities are present in Fanconi’s anaemia?

Answer 7

Macrocytosis –> thrombocytopaenia –> neutropaenia

Question 8

What are patients with Fanconi’s anaemia at risk of developing?

Answer 8

Leukaemia

Question 9

List the main acquired primary bone marrow failures that result in pancytopenia

Answer 9

Aplastic anaemia
Myelodysplasia
Acute leukaemia

Question 10

What happens in aplastic anaemia?

Answer 10

Autoimmune T cell attack against haemopoietic stem cells, damaging myeloid cells

Question 11

What are the histological features of anaplastic anaemia?

Answer 11

Absence of haemopoeitic cells

Fat and fibrosis (white tisse)

Question 12

List histological features of myelodysplastic syndrome

Answer 12

Dysplasia causing production of bizarre cells
Hypercellular marrow
Increased apoptosis of progenitor and mature cells

Question 13

What is the pathogenesis of myelodysplasia?

Answer 13

Acquired DNA mutations in haematopoietic stem cells leading to ineffective haemopoeisis causing disordered development of blood cells

Question 14

What condition does myelodysplasia have the potential to evolve into?

Answer 14

Acute myeloid leukaemia

Question 15

How does an acute leukaemia cause pancytopaenia?

Answer 15

Proliferation of abnormal blasts from stem cells leads to failure of differentiation of normal blood cells
Hijacking of the HSC niche and marrow environment

Question 16

List the main causes of secondary bone marrow failure

Answer 16

Drugs (chemotherapy, chloramphenicol)
B12/folate deficiency
Infiltration
Infection (viral, HIV)
Storage diseases

Question 17

List conditions causing increased destruction of blood cells

Answer 17

Hypersplenism (sequestration)
Sepsis
Immune

Question 18

What cell process within the spleen is overworking in hypersplenism?

Answer 18

Cords contain macrophages that detect, retain and eliminate unwanted, foreign or damaged material, including cells

Question 19

List some causes of hypersplenism

Answer 19

Splenic congestion (heart failure, portal hypertension)
Rheumatoid arthritis
Felty’s syndrome
Splenic lymphoma

Question 20

List clinical features of pancytopenia (think anaemia, neutropenia and thrombocytopenia)

Answer 20

Fatigue
Breathlessness
Infection
Bleeding
Purpura, rash

Question 21

List investigations for pancytopenia

Answer 21

Family history
Blood count and film
Guided tests (LFTs, folate/B12, virology, antibodies)
Cytogenetics
Bone marrow examination (aspirate, trephine biopsy)

Question 22

Outline supportive treatment for pancytopenia

Answer 22

Blood transfusion (red cells, platelets, neutrophils)
Prophylactic antibiotics (Gram negative cover)

Question 23

In treatment of neutropenic fever, antibiotics should be given promptly without waiting on results. True/ False?

Answer 23

True

Question 24

Outline treatment for pancytopenia caused by primary marrow disorder

Answer 24

Chemotherapy in malignancy
Bone marrow transplant in congenital causes
Immunosuppression in aplastic anaemia

Question 25

Outline treatment for pancytopenia caused by secondary marrow disorder

Answer 25

Stop precipitants
Treat infection
Replace B12/folate

Question 26

Outline treatment for pancytopenia caused by hypersplenism

Answer 26

Treat cause if possible

Consider splenectomy –> vaccination

Question 27

The bone marrow would appear hypocellular in…

Answer 27

LOTS OF FAT
Aplastic anaemia
Drug induced aplasia e.g. cytotoxics

Question 28

The bone marrow would appear hypercellular in…

Answer 28

NOT MUCH FAT
Myelodysplastic syndromes
B12/folate deficiency
Hypersplenism
Infiltration

Question 29

List causes of neutropaenia

Answer 29

Bacterial infection
Inflammation e.g. RA
Trauma/ post-op
Corticosteroids
Myeloproliferative disease