Aplastic Anaemia

Question 1

What are the causes of Pancytopenia?

Answer 1

• Decreased bone marrow function.
• Aplasia (reduction of haemopoietic stem cells)
• Acute leukaemia, myelodysplasia, myeloma.
• Infiltration with lymphoma, solid tumours, tuberculosis.
• Megaloblastic anaemia.
• Paroxysmal nocturnal haemoglobinuria
• Myelofibrosis
• Haemophagocytic syndrome.
• Increased peripheral destruction
• Splenomegaly

Question 2

What is Pancytopenia?

Answer 2

Pancytopenia is a reduction in the blood count of all the major cell lines – red cells, white cells and platelets.

Question 3

What is Aplastic Anaemia?

Answer 3

Aplastic Anaemia is defined as pancytopenia resulting from hypoplasia of the bone marrow.

Question 4

What is the pathogenesis of Aplastic anaemia?

Answer 4

A substantial reduction in the number of haemopoietic pluripotential stem cells, and a fault in the remaining stem cells or an immune reaction against them, which makes them unable to divide and differentiate sufficiently to populate the bone marrow and blood.

Question 5

True or False? Fanconi Anaemia is Autosomal Dominant.

Answer 5

FALSE!! It is Autosomal recessive .

Question 6

What are the clinical features of Fanconi Anaemia?

Answer 6

• Growth retardation
• Congenital defects of the skeleton (e.g. microcephaly, absent radii or thumbs)
• Pelvic or horseshoe kidney
• Skin areas of hyper- and hypopigmentation
• Might be a learning disability but intelligence is normal.

Question 7

How many different genes can be involved with Fanconi Anaemia?

Answer 7

16

Question 8

What is the diagnostic test for Fanconi Anaemia?

Answer 8

• An elevated breakage after incubation of peripheral blood lymphocytes with a DNA cross-linking agent such as diepoxybutane (DEB test) or mitomycin C.

Question 9

What is the age range for the usual presentation of Fanconi Anaemia?

Answer 9

Age 3-14 years

Question 10

What is the treatment for patients with Fanconi Anaemia?

Answer 10

Treatment is usually with androgens or stem cell transplantation (SCT).

Question 11

What are the Primary Causes of Aplastic Anaemia?

Answer 11

• Congenital (Fanconi anaemia, other inborn marrow failure syndromes)
• Idiopathic acquired, usually with an autoimmune pathophysiology

Question 12

What is the classic triad of Dyskeratosis congenita (DKC) ?

Answer 12

• Nail dystrophy
• Lacy reticular pigmentation of the upper chest and neck
• Oral leukoplakia.

Question 13

True or False? There is a high risk of pulmonary fibrosis, cirrhosis, osteoporosis, marrow failure and epithelial cancer (e.g. oral, oesophageal, uterine cervix) associated with Dyskeratosis Congenital (DKC)?

Answer 13

TRUE!!

Question 14

What are the genetic mutations associated with Dyskeratosis Congenita (DKC)?

Answer 14

• DKC1 (dyskerin),
• TERC (telomerase reverse transcriptase RNA template)
• TERT or other genes encoding components of telomerase ( enzyme involved in maintaining telomere length )

Question 15

How is the diagnosis for Dyskeratosis Congenita (DKC) done?

Answer 15

Diagnosis is by measuring length of lymphocyte telomeres and by by genetic testing for mutations in telomere complex genes.

Question 16

What is the treatment for Dyskeratosis Congenita DKC)?

Answer 16

• Androgens can improve blood count & may lengthen telomeres
• SCT can cure the marrow failure

Question 17

What is the genetic mutation associated with Shwachman–Diamond syndrome?

Answer 17

SBDS, involved in ribosome assembly

Question 18

True or False? Shwachman–Diamond syndrome is Autosomal Recessive.

Answer 18

TRUE!!

Question 19

What are the clinical features of Shwachman - Diamond Syndrome?

Answer 19

• Cytopenia
• Neutropenia
• Short Stature
• Exocrine pancreatic dysfunction
• Hepatic impairment
• Skeletal Abnormalities

Question 20

What are the clinical features associated with GATA 2 mutations?

Answer 20

• Warts
• Monocytopenia
• Lymphoedema

Question 21

What are the genetic mutations associated with Idiopathic acquired aplastic anaemia?

Answer 21

• acquired mutation in the STAT3 signalling pathway
• Clonal haemopoiesis occurs in 50% of cases with somatic mutations of genes including PIGA, BCOR, BCORL1, ASXLI, RUNX1 or DNMT3A, or loss of human leukocyte antigen (HLA) class I expression.

Question 22

Which antimetabolite drugs causes Temporary Aplasia?

Answer 22

• Methotrexate) and mitotic inhibitors (e.g. daunorubicin)

Question 23

Which drugs causes more prolonged aplasia closely resembling idiopathic aplastic anaemia?

Answer 23

Busulphan

Question 24

What are the Clinical Features associated with Aplastic Anaemia?

Answer 24

• 10–25 and over 60 years
• More frequent in Asia
• It can be insidious or acute
• Anaemia, Neutropenia or thrombocytopenia.
• Bruising
• Bleeding gums, epistaxes and menorrhagia
• Retinal haemorrhage may impair vision
• The lymph nodes, liver and spleen are NOT enlarged

Question 25

What are the laboratory findings of Aplastic Anaemia?

Answer 25

■ Anaemia (haemoglobin <100g/L). This is normo-
chromic, normocytic or macrocytic, with mean cell volume (MCV) often 95–110fL.

• The reticulocyte count is usually EXTREMELY LOW in relation to the degree of anaemia.
  ■ Neutrophil count <1.5 × 109/L.
  ■ Platelet count <50 × 109/L.
  Severe cases are defined by neutrophils <0.5×109/L and platelets <20×109/L, reticulocytes <20×109/L and marrow cellularity <25%. Very severe cases also show neutrophils <0.2 × 109/L.

2. There are no abnormal cells in the peripheral blood that would indicate leukaemia.
3. The bone marrow shows hypoplasia - with loss of haemopoietic tissue and replacement by fat which comprises over 75% of the marrow.
4. Main cells are lymphocytes and plasma cells ; Megakaryocytes are significantly Reduced.

Question 26

Which treatment for Aplastic anaemia is prepared by immunizing animals (usually horse or rabbit in the West, pig in China) with human thymocytes ?

Answer 26

Anti-thymocyte globulin (ATG), also called anti-lymphocyte globulin (ALG)