Bone Marrow Failure

Question 1

• 6 month old baby presents with low Hb, low reticulocytes, impaired growth, and craniofacial and cardiac abnormalities. Normal WCC and platelets
  - What is the most likely diagnosis?

Answer 1

-Diamond Blackfan anaemia (Congential pure red cell aplasia)

Question 2

• 8 year old child presents with anaemia, neutropenia and thrombocytopenia, dysplasia of the radius
• What is the most likely diagnosis?

Answer 2

-Fanconi Anaemia (Bone marrow failure syndrome)

Question 3

Give 3 causes of acquired red cell aplasia

Answer 3

• Parvovirus B19
  - EPO therapy
  - Autoimmune disorder

Question 4

What is the main treatment for acquired Pure red cell aplasia (PRCA)?

Answer 4

• Thymectomy
• Immunosuppression
• Supportive blood product transfusions

Question 5

Outline the pathophysiology of anaemia of chronic disease

Answer 5

• Prolonged inflammatory, infectious or neoplastic disease causes a complex pathogenesis thought to be mediated by inflammatory cytokines
• Reduced BFUe (Erythroid burst forming unit) and CFUe (Erythroid colony forming unit) caused by cytokines including interferon alpha, beta and gamma.
• Dysregulation of iron metabolism leads to excessive storage of iron in the bone marrow, with low serum iron

Question 6

Name some Infectious causes of haemolysis? (3)

Answer 6

• Malaria
  - Babesiosis
  - Clostridial infection
  - Paroxysmal cold haemoglobinuria
  - Haemolytic uraemic syndrome (E. coli)

Question 7

How does Parvovirus B19 lead to pure red cell aplasia?

Answer 7

Infection can occur via respiratory tract, blood products or placenta

• The virus has a high degree of erythroid cell tropism. It is able to enter pro-erythroblasts via P-antigen
• Expression of non-structural protein (NS1) causes induction and activation of caspase cascade and apoptosis of erythroid cells.
• NS1 also causes arrest of cell cycle at G1, causing a reduced proliferation of red cells
• This leads to underproduction of RBCs (ie Pure red cell aplasia)

Question 8

How does HIV lead to cytopenia/bone marrow failure?

Answer 8

• Viruses can affect progenitor cells directly
  - Opportunistic infections or HIV virus can infiltrate the bone marrow
  - HIV medications also contribute

Question 9

How can infection lead to bone marrow failure?

Answer 9

(parvovirus B19 as an example)
Infection can occur via respiratory tract, blood products or placenta
-The virus has a high degree of erythroid cell tropism. It is able to enter pro-erythroblasts via P-antigen
-Expression of non-structural protein (NS1) causes induction and activation of caspase cascade and apoptosis of erythroid cells.
-NS1 also causes arrest of cell cycle at G1, causing a reduced proliferation of red cells
-This leads to pure red cell aplasia

Question 10

How is EPO therapy associated with PRCA?

Answer 10

• Recombinant EPO can give rise to cross-reacting antibodies between recombinant EPO and endogenous EPO.
• Reduced endogenous EPO leads to reduced RBC production