Aplastic anaemia

Question 1

definition of aplastic anaemia

Answer 1

Characterized by diminished haematopoietic precursors in the bone marrow and deficiency of all blood cell elements (pancytopaenia).

stem cell disorder - bone marrow stops making cells = pancytopenia

Question 2

aetiology of aplastic anaemia

Answer 2

idiopathic >40% - destruction or suppression of stem cell by autoimmune mechanisms

acquired

inherited

Question 3

acquired causes of aplastic anaemia

Answer 3

drugs - chloramphenicol, gold, alkylating agents, antiepileptics, sulphonamides, methotrexate, nifedipine

chemicals - DDT, benzene

radiation

viral infection (B19 parvovirus, HIV, EBV, hepatitis)

paroxysmal nocturnal haemoglobinuria

Question 4

inherited causes of aplastic anaemia

Answer 4

fanconi’s anaemia

dyskeratosis congenita

Question 5

fanconi’s anaemia

Answer 5

rare autosomal recessive/X linked - error of stem cell DNA repair and chromosomal fragility = aplastic anaemia:

Characterized by

• familial aplastic anaemia,
• short stature,
• abnormality of thumbs,
• cafe au lait spots,
• microcephaly,
• hypogonadism
• hypopit
• renal tract defects.
• high risk of AML and breast ca (BRCA2)
• skin pigmentation
• absent radii
• syndactyly
• deafness
• cryptorchidism
• low IQ

Question 6

dyskeratosis congenita

Answer 6

associated with reticulated hyperpigmented rash, nail dystrophy and mucosa leukoplakia

Question 7

epidemiology of aplastic anaemia

Answer 7

Annual incidence: 2–4 in 1,000,000.

Can occur at any age.

Slightly more common in males.

Question 8

sx of aplastic anaemia

Answer 8

onset over months/days

anaemia = tiredness, lethargy, dyspnoea

thrombocytopenia - easy bruising, bleeding gums, epistaxis

leukopenia - increased frequency and severity of infections

Question 9

signs of aplastic anaemia

Answer 9

anaemia - pale

thrombocytopenia - petechiae, bruises

leukopenia - multiple bacterial/fungal infections. No hepatomegaly, splenomegaly or lymphadenopathy

Question 10

Ix for aplastic anaemia

Answer 10

blood

blood film

bone marrow trephine biopsy - diagnostic

Question 11

blood results in aplastic anaemia

Answer 11

low Hb, platelets, WCC

normal MCV

low or absent reticulocytes

Question 12

blood film in aplastic anaemia

Answer 12

to exclude leukaemia - absence of abnormal circulating white blood cells

Question 13

bone marrow trephine biopsy in aplastic anaemia

Answer 13

needed for diagnosis

trephine is a core of bone from posterior iliac crest - allow assessment of bone marrow cellularity, architecture and presence of infilrative disease

hepatocellular marrow decrease in all elements, marrow space is composed mostly of fat cells and marrow stroma

exclusion of lymphoma, leukaemia, malignancies, myeloma, myelofibrosis

Question 14

criteria for severe aplastic anaemia

Answer 14

Marrow showing <25 % of normal cellularity,

OR Marrow showing <50 % of normal cellularity, <30% of the cells are haematopoietic plus 2 of the following:

• neutrophils<0.5x10(9)/L
• platelets <20x10(9)/L
• reticulocytes <40x10(9)/L

Question 15

Ix for Fanconi’s anaemia

Answer 15

Presence of increased chromosomal breakage in lymphocytes cultured in the presence of DNA cross-linking agents e.g. mitomycin C.

Question 16

role of bone marrow normally

Answer 16

responsible for haematopoiesis

normally in central skeleton (vertebrae, sternum, ribs, skull) and prox long bones

all blood cells arise form early pluripotent stem cell, which divides asymmetrically to produce another stem cell and a progenitor cell committed to a lineage

they differentiate into myeloid or lymphocyte lineages - releasing their progeny into the blood

Question 17

agranulocytosis

Answer 17

granulocytes (WBCs with neutrophil, basophil, or eosinophil granules) have stopped being made

= risk of fatal infections

caused by drugs

warn to report any fever

neutropenia may present as a sore throat