Pancytopenia

Question 1

Define pancytopenia

Answer 1

Deficiency of blood cells of all lineages (excludes lymphocytes)

Question 2

Pancytopenia can include either reduced production or increased destruction. Give examples of reduced production

Answer 2

Acquired (primary and secondary) bone marrow failure

Inherited syndrome

Question 3

Characteristics of inherited marrow failure syndrome

Answer 3

Arise due to defects in DNA repair/ribsosomes/telomeres

Question 4

What is an example of an inherited bone marrow failure

Answer 4

Fanconi’s anaemia

Question 5

Short stature
Skin pigment abnormalities
Radial ray abnormalities
Café au lait spots
Hypogenitilia
Endocrine, GI, CVD, renal and haem abnormalities

Answer 5

Fanconi’s anaemia

Question 6

Pathophysiology of inherited bone marrow failure

Answer 6

Unable to correct inter-strand cross-links (DNA damage)

Consists of macrocytosis followed by thrombocytopenia, then neutropenia

Question 7

Mode of transmission of Fanconi anaemia

Answer 7

Autosomal recessive

Question 8

Fanconi anaemia imposes an increased risk of..

Answer 8

Acute myeloid leukaemia

Question 9

Haematological problems seen in Fanconi anaemia

Answer 9

Aplastic anaemia

Question 10

Give examples of acquired primary bone marrow failure

Answer 10

Idiopathic aplastic anaemia
Myelodysplastic syndromes
Acute leukaemia

Question 11

Aplastic anaemia is characterised by..

Answer 11

Pancytopenia and a hypoplastic bone marrow

Question 12

Normochromic, normocytic anaemia
Leukopenia, with lymphocytes relatively spared thrombocytopenia

Answer 12

Aplastic anaemia

Question 13

Aplastic anaemia may be the presenting feature in..

Answer 13

Acute lymphoblastic or myeloid leukaemia

Question 14

A minority of patients with aplastic anaemia later develop..

Answer 14

Paroxysmal nocturnal haemoglobinuria or myelodysplasia

Question 15

Causes of aplastic anaemia

Answer 15

Fanconi anaemia, dyskeratosis congenita
Cytotoxics, chloramphenicol, sulphonamides, phenytoin, gold
Benzene
Parvovirus, hepatitis
Radiation

Question 16

Pathophysiology of idiopathic aplastic anaemia

Answer 16

Auto-reactive T cells release inflammatory cytokines (IFN-ᵞ
TNF-α) leading to pancytopenia and a hypoplastic bone marrow

Question 17

Define myelodysplastic syndromes

Answer 17

Heterogeneous group of clonal hematopoietic stem cell disorders, characterised by ineffective hematopoiesis and peripheral blood cytopenias

Question 18

Myelodysplastic syndromes can progress to..

Answer 18

Acute myeloid leukaemia (AML)

Question 19

What are the secondary causes of hematopoietic stem cells and when do they develop?

Answer 19

Chemotherapy and radiotherapy

Develops around 5 years post-treatment

Question 20

The key pathophysiological feature of MDS is..

Answer 20

Ineffective hematopoiesis leading to peripheral cytopenias despite a typically hypercellular bone marrow

Question 21

Ix for MDS

Answer 21

Peripheral blood counts
Bone marrow biopsy
Cytogenetic analysis

Question 22

Dysplastic changes in hematopoietic cells and a varying degree of blasts

Answer 22

MDS

Question 23

Tx for MDS

Answer 23

Supportive treatment (e.g., blood or platelet transfusions)
Erythropoietin
Granulocyte colony-stimulating factor
Chemotherapy and targeted therapies (e.g., lenalidomide)
Allogenic stem cell transplantation

Question 24

Increased apoptosis of progenitor and mature cells

Answer 24

MDS

Question 25

Why can acute leukaemia cause pancytopenia?

Answer 25

Proliferation of abnormal cells (blasts) from leukaemic stem cells Failure to differentiate or mature into normal cells Prevent normal haemopoietic stem/ progenitor (HSC) development by ‘hijacking’/ altering the haemopoietic niche and marrow microenvironment

Question 26

Give examples of causes of secondary bone marrow failure

Answer 26

Drugs (chemotherapy, alcohol, azathioprine, methotrexate chloramphenicol) B12/folate deficiency Non-haemopoietic malignant infiltration, lymphoma Viral (eg HIV)/storage diseases

Question 27

Pancytopenia can include either reduced production or increased destruction. Give examples of increased destruction

Answer 27

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

Question 28

What causes hyperplenism?

Answer 28

Splenic congestion - portal hypertension Systemic diseases - RA Haematological - splenic lymphoma

Question 29

Clinical features of pancytopenia

Answer 29

Anaemia Neutropenia Thrombocytopenia

Question 30

Hypocellularity in bone marrow is normally seen in..

Answer 30

Aplastic anaemia

Question 31

Hypercellularity in bone marrow is normally seen in..

Answer 31

Myelodysplastic syndromes B12/folate deficiency Hypersplenism

Question 32

Tx in pancytopenia

Answer 32

Supportive - red, platelet, neutrophils transfusions Antibiotics prophylaxis/treatment

Question 33

Tx in congenital primary bone marrow disorder

Answer 33

Allogeneic stem cell transplantation

Question 34

Tx in idiopathic aplastic anaemia

Answer 34

Immunosuppression

Question 35

Tx in secondary bone marrow disorder

Answer 35

Drug reaction – STOP Viral – eg treat HIV Replace B12/folate