Pancytopenia

Question 1

What diagnosis is least likely?

AML
ALL
Aplastic anaemia
Myelodysplastic syndrome
Myeloproliferative disorder / neoplasm

Answer 1

Myeloproliferative disorder / neoplasm

Characterised by excessive proliferation of marrow cells and therefore an increase in cell numbers over the normal reference range

Question 2

What is the likely reason for low blood counts?

AML
B12 deficiency
Folate toxicity
Hypersplenism
Aplastic anaemia

Answer 2

Hypersplenism
Patients with chronic liver disease / cirrhosis can develop portal hypertension and splenomegaly in which blood cells are trapped. Therefore number of blood cells in circulation is reduced

High serum folate is likely to reflect oral folate supplementation

Question 3

What is pancytopenia?

Answer 3

A deficiency of blood cells of all lineages (but generally excludes lymphocytes)

Question 4

Is pancytopenia a diagnosis?

Answer 4

NO - reflects d iagnosis

Note: pancytopenia does not always mean bone marrow failure or malignancy

Question 5

What are causes of pancytopenia?

Answer 5

Reduced production OR
increased destruction

Question 6

What are causes of reduced production in pancytopenia?

Answer 6

Bone marrow failure
- Inherited syndromes
- Acquired: primary & secondary

Question 7

How do inherited marrow failure syndromes occur?

Answer 7

Question 8

What is a very rare inherited marrow failure syndrome?

Answer 8

Fanconi’s anaemia

Question 9

What are symptoms of fanconi’s anaemia?

Answer 9

Short stature
Skin pigment abnormalities
Hypogenitalia
Endocrinopathies
GI defects
Skeletal abnormalities
Cafe au lait spots

Question 10

What are haematological abnormalities that can cause bone marrow failure

Answer 10

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

Macrocytosis followed by thrombocytopenia, then neutropenia

Question 11

What are acquired primary bone marrow failures?

Answer 11

Intrinsic marrow problems:

• Idiopathic aplastic anaemia (autoimmune attack against HSCs)
• Myelodysplastic syndrome
• Acute leukemia (total WCC can be high due to an excess of circulating blasts but patients can present with pancytopenia)

Question 12

What is aplastic anaemia pathogenesis?

Answer 12

Question 13

What are myelodysplastic syndromes?

Answer 13

Clonal haemopoeitic stem cell disorder characterised by dysplasia (disordered development) or unique genetic abnormalities

Hypercellular marrow

Increased apoptosis of progenitor and mature cells (ineffective haemopoeisis)

Not all patients have pancytopenia - isolated anaemia is most common

Question 14

Myelodysplastic syndromes can evolve into?

Answer 14

Acute myeloid leukemia (AML)

Question 15

Why can acute leukemia cause pancytopenia?

Answer 15

Proliferation of abnormal cells (blasts) from leukaemia stem cells (LSC)

Failure to differentiate or mature into normal cells

Prevent normal HSC development by hijacking / altering the haemopoeitic niche and marrow microenvironment

Question 16

What are causes of secondary bone marrow failure?

Answer 16

Drug induced (chemotherapy, alcohol, azathioprine, methotrexate, chloramphenicol) - causes aplasia

B12 / flate deficiency (nuclear maturation can affect all lineages) (hyper cellular marrow)

Infiltrative - non haemopoeitic malignant infiltration, lymphoma

Miscellaneous: viral (e.g. HIV)/storage diseases

Question 17

What are causes of pancytopenia where there is increased destruction?

Answer 17

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

Question 18

Any cause of splenomegaly can potentially result in hypersplenism. True or false?

Answer 18

Yes

Splenic size alone may not always correlate with hypersplenism

Question 19

What are causes of hypersplenism?

Answer 19

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

Question 20

Draw out how pancytopenia causes can be determined

Answer 20

Question 21

What is pancytopenia?

Answer 21

Anaemia + neutropenia + thrombocytopenia

Question 22

What are clinical features of pancytopenia?

Answer 22

Anaemia - fatigue, SOB, cardiovascular compromise

Neutropenia - infections

Thrombocytopenia - bleeding (purpura, petechiae, wet bleeds)

Question 23

How do we establish cause of pancytopenia?

Answer 23

History, including FHx
Clinical findings
FBC, blood film
Additional routine tests guided by above (B12/folate), LFTs, virology, autoantibody tests
Bone marrow examination
Specialised tests guided by above (cytogenetics e.g. chromosome fragility testing in fanconi’s syndrome, NGS, WGS)

Question 24

Describe when marrow cellularity is hypo cellular compared to hyper cellular in pancytopenia

Answer 24

Hypocellular - aplastic anaemia
Hypercellular - myelodysplastic syndromes, B12/folate deficiency, hypersplenism

Question 25

How do we treat pancytopenia?

Answer 25

Supportive - red cell transfusion, platelet transfusion Antibiotic prophylaxis / treatment - antibacterials, antifungals Treat neutropenic fever promptly based on local unit antibiotic policy without waiting for (microbiology) results

Question 26

What are primary bone disorder treatments?

Answer 26

Malignancy - consider chemotherapy Congenital - consider allogenic stem cell transplantation Idiopathic aplastic anaemia - immunosuppression MDS - depends on risk of leukemic transformation, erythropoeisis-stimulating agents in low risk, demethlyating agents or chemotherapy in higher risk

Question 27

What are treatments for secondary bone marrow disorders?

Answer 27

Drug reaction - STOP Viral - treat HIV Replace B12 / folate

Question 28

How do we treat hypersplenism?

Answer 28

Treat cause if possible Consider splenectomy (not appropriate in all cases)