Week 2- pancytopenia

Question 1

What is pancytopenia?

Answer 1

A deficiency of blood cells of all lineages (however generally excludes lymphocytes). This means low RBC, low platelets, low neutrophils.

Question 2

For steady state in blood cells, what does it need to be?

Answer 2

Cell production needs to equal cell destruction.

Question 3

what is the lifespan of RBCs?

Answer 3

120 days

Question 4

What is the lifespan of platelets?

Answer 4

7-10 days

Question 5

What is the lifespan of neutrophils?

Answer 5

7-8 hours.

Question 6

Using general principles, what are the causes of pancytopenia?

Answer 6

Decreased production or increased destruction.

Question 7

What are causes of reduced production in pancytopenia?

Answer 7

Bone marrow failure- could be inherited or acquired.

Acquired can be further divided into primary and secondary.

Question 8

Are inherited marrow syndromes common?

Answer 8

No they are very rare.

Question 9

What is the presentation of Fanconi’s syndrome?

Answer 9

Short stature
Skin pigment abnormalities- cafe au lait
Radial ray abnormalities
Hypogenitalia
Endocrinopathies
GI defects 
Cardiovascular
Renal
Haematological

Question 10

What are the haematological abnormalities seen in Falconi’s syndrome?

Answer 10

These arise around the age of 7, the patient is unable to correct inter strand cross links (DNA damage)
You get macrocytosis followed by thrombocytopenia followed by neutropenia.
Bone marrow failure (aplasia)

Question 11

What are the primary causes of acquired reduced production in pancytopenia?

Answer 11

Usually a stem cell defect- however no obvious cause.

Question 12

What are the primary causes of acquired bone marrow failure?

Answer 12

Usually a stem cell defect causing an intrinsic marrow problem however no obvious cause. 
Idiopathic aplastic anaemia- autoimmune attack against haemopoetic stem cells
Myelodysplastic syndromes
Acute leukaemia (white cell count can be variable)

Question 13

Describe the pathogenesis of aplastic anaemia?

Answer 13

Auto-reactive T cells attack haemopoetic stem cells of myeloid lineage leading to no maturation and therefore no neutrophils, RBC’s and platelets.

Question 14

What will the bone marrow of aplastic anaemia show?

Answer 14

Severely hypocellular.

Question 15

What is myelodysplastic syndrome?

Answer 15

Blast cells in the blood/bone marrow due to them not being able to mature. You get increased apoptosis of progenitor and mature cells.
Propensity for evolution into AML.

Question 16

Why can acute leukaemia cause pancytopenia?

Answer 16

In acute leukaemia you get proliferation of abnormal immature cells. These fail to mature into normal cells and prevent normal haemopoetic stem cells from developing by hijacking the haemopoetic niche and marrow microenvironment.

Question 17

What can cause secondary bone marrow failure?

Answer 17

Drug induced e.g. chemotherapy, chloramphenicol
B12/folate deficiency
Viral e.g. HIV
Infiltrative non-haemopoetic malignant infiltration

Question 18

What can cause increased destruction of blood cells leading to pancytopenia?

Answer 18

Hypersplenism- increased splenic pool or increased destruction exceeding bone marrow capacity, usually associated with a significantly enlarged spleen.

Question 19

What can cause hypersplenism?

Answer 19

Splenic congestion- portal hypertension, congestive cardiac failure
Systemic disease e.g. RA
Haematological diseases e.g. splenic lymphoma.

Question 20

What clinical features are associated with pancytopenia?

Answer 20

Signs and symptoms can reflect the lack of circulating blood cells and the cause of the pancytopenia.

Question 21

What are the three things making up pancytopenia?

Answer 21

Anaemia
Neutropenia
Thrombocytopenia

Question 22

What signs and symptoms are seen with anaemia?

Answer 22

Fatigue
Shortness of breath
Cardiovascular compromise

Question 23

What signs and symptoms are associated with neutropenia?

Answer 23

Infections

Question 24

What signs and symptoms are associated with thrombocytopenia?

Answer 24

Bleeding
Purpura
Petechiae
‘Wet’ bleeds including visceral bleeds.

Question 25

How can you establish the cause of pancytopenia?

Answer 25

Hx- inc family Hx
Clinical findings
FBC, blood film
B12/folate, LFTS, virology, autoantibody testing
Bone marrow examination

Question 26

What will the marrow cellularity be like in aplastic anaemia?

Answer 26

Hypocellular.

Question 27

What will the marrow cellularity be like in myelodysplastic disorders?

Answer 27

Hypercellular- lots of immature cells.

Question 28

What will the marrow cellularity be like in B12/folate deficiency?

Answer 28

Hypercellular- lots of immature cells. Issue is that they don’t have the means to mature.

Question 29

How do you treat pancytopenia?

Answer 29

Dependent on the cause.

Also supportive treatment.

Question 30

What supportive measures would you use for pancytopenia?

Answer 30

Red cell transfusions
Platelet transfusions
Antibiotics prophylactically

Question 31

What specific therapy would you use for primary bone marrow failures?

Answer 31

If malignancy- consider chemotherapy
If congenital- consider bone marrow transplantation
Idiopathic aplastic anaemia- immunosuppression

Question 32

How would you treat secondary bone marrow disorders?

Answer 32

If its a drug- stop it
If its viral- supportive
Replace B12/folate

Question 33

How do you treat hypersplenism?

Answer 33

Treat cause

Consider splenectomy