1.5 Red cell disorders 2: aplastic anaemia, myelodysplastic syndrome

Question 1

Define aplasia

Answer 1

No tissue

Question 2

Define Dysplasia

Answer 2

Bad tissue

Question 3

Define hyperplasia

Answer 3

More tissue than normal

Question 4

Define hypoplastic

Answer 4

Less tissue than normal

Question 5

define pancytopenia

Answer 5

reduction in all cell types (red, white and platelets)

Question 6

What are the possible causes of bone marrow aplasia?

Answer 6

Genetic: Fanconi anaemia, dyskeratosis congenita

Drugs: antibiotics, anti-inflammatory, anti-convulsants, anti-thyroid, anti-cancer, anti-diabetics, antidepressants

Chemicals: benzene, nitrogen mustard

Radiation

Infection: non-A, non-B, non-C viral hepatitis

Immune in 70-80% cases

Question 7

define aplastic anaemia

Answer 7

Pancytopenia resulting from aplasia of the bone marrow

Question 8

What antigen is over represented in aplastic anaemia?

Answer 8

HLA-DR2

Question 9

What are the clinical features of aplastic anaemia?

Answer 9

Anaemia: tiredness, lethargy, dyspnoea, reduced exercise tolerance, cardiac failure

Thrombocytopenia: bleeding or bruising

Neutropenia: cutaneous and deep-seated infections, opportunistic infections

Question 10

What are the clinical features of aplastic anaemia?

Answer 10

Anaemia: tiredness, lethargy, dyspnoea, reduced exercise tolerance, cardiac failure

Thrombocytopenia: bleeding or bruising

Neutropenia: cutaneous and deep-seated infections, opportunistic infections

Question 11

What tests do you need to do for suspected aplastic anaemia?

Answer 11

• FBC and reticulocyte count
• Blood film examination
• HbF% in children
• Bone marrow aspirate, cytogenetics
• Peripheral blood chromosomal breakage to exclude Fanconi anaemia
• Flow cytometry for GPI-anchored proteins
• Vitamin B12 and folate
• LFT (hepatits)
• Viral: hepatitis, EBV, HIV
• ANti-nuclear antibody and anti-dnDNA
• Chest x-ray (infections and pneumonia)
• Abdominal US and echo
• Peripheral blood gene mutation analysis for dyskeratosis congenital

Question 12

What tests do you need to do for suspected aplastic anaemia?

Answer 12

• FBC and reticulocyte count
• Blood film examination
• HbF% in children
• Bone marrow aspirate, cytogenetics
• Peripheral blood chromosomal breakage to exclude Fanconi anaemia
• Flow cytometry for GPI-anchored proteins
• Vitamin B12 and folate
• LFT (hepatits)
• Viral: hepatitis, EBV, HIV
• ANti-nuclear antibody and anti-dnDNA
• Chest x-ray (infections and pneumonia)
• Abdominal US and echo
• Peripheral blood gene mutation analysis for dyskeratosis congenital

Question 13

What is the initial treatment for aplastic anaemia?

Answer 13

Transfusion of red cells and platelets
Treatment of neutropenic sepsis and shock
Prevent infections
Long term IV line if needed

Question 14

What are the non transplant options for aplastic anaemia?

Answer 14

Immunosuppressive therapy with rabbit-ATG, cyclosporin and steroids to knock out T cells
Oxymethalone

Question 15

What are the complications of allografts?

Answer 15

Graft vs. host disease 
graft failure/rejection 
Immunosuppression 
Opportunistic infection 
second malignancies 
Infertility

Question 16

Define myelodysplastic syndrome

Answer 16

A heterogenous group of clonal disorders of haemopoietic stem cells leading to ineffective haematopoiesis

Question 17

What are the causes of myelodysplastic syndrome?

Answer 17

Prior chemotherapy
Complication of IAA
Any cause of leukaemia

Question 18

What is the pathophysiology of myelodysplastic syndrome?

Answer 18

Acduired gene mutations in multi potent stem cells which leads to the blockage of maturation, development and/or differentiation

Question 19

What are the clinical features of myelodysplastic syndrome?

Answer 19

Those of bone marrow failure (same as AA)

- Anaemia, thrombocytopenia, neutropenia

Question 20

What are the laboratory findings of myelodysplastic syndrome?

Answer 20

Cytopenia
Macrocytosis

RC: basophilic stippling, dimorphism, Nucleated RBC, Shape abnormalities

Myeloid morphology: pseudo-Pelger-Huet anomaly, hypergranulaton, blasts

Platelets: giant and agranular

Raised reticulocyte and LDH

Question 21

What is the pathophysiology of myelodysplastic syndrome?

Answer 21

Acquired gene mutations in multi potent stem cells which leads to the blockage of maturation, development and/or differentiation

Question 22

What are the laboratory findings of myelodysplastic syndrome?

Answer 22

Cytopenia
Macrocytosis

RC: basophilic stippling, dimorphism, Nucleated RBC, Shape abnormalities

Myeloid morphology: pseudo-Pelger-Huet anomaly, hypergranulaton, blasts

Platelets: giant and agranular

Raised reticulocyte and LDH

Marrow: ring spiderblasts, iron granules

Question 23

What will flow cytometry show in myelodysplastic syndrome?

Answer 23

CD34+ blast count (blasts will be an indication of leukaemia)

Question 24

what are the cytogenetics of myelodysplastic syndrome

Answer 24

5q-, 7q- mutated SF3B1

Question 25

What is the initial treatment of myelodysplastic syndrome?

Answer 25

Transfusion of red cells
Transfusion of platelets
Treat neutropenic sepsis and shock
Prevent infections

Question 26

What is the further management of myelodysplastic syndrome?

Answer 26

Transfusions 
Iron chelation 
Epo 
GCSF 
Thrombopoietin analogues 
Treat and prevent opportunistic infections

Question 27

When do you use Lenalidomide and what dose?

Answer 27

myelodysplastic syndrome patients with 5q- low/intermediate risk

10mg daily for 21/28 days

Question 28

What is Azacitidine used for and who benefits the most?

Answer 28

myelodysplastic syndrome patients with 7q, -5 -7