Pancytopaenia

Question 1

what is pancytopenia?

Answer 1

deficiency of blood cells of all lineages (bute generally excludes lymphocytes)

Question 2

is pancytopenia a diagnosis?

Answer 2

no
just reflects another diagnosis
(but does not always mean bone marrow failure)

Question 3

steady state?

Answer 3

cell production = cell destruction

Question 4

cell intermediates in erythropoiesis?

Answer 4

pronormoblast > basophilic/early normoblast > polychromatophilic/intermediate normoblast > orthochromatic/late normoblast > reticulocyte > mature RBC/erythrocyte

Question 5

how many RBCs made per second?

Answer 5

2.5 million

Question 6

how many neutrophils mad per second?

Answer 6

1-2 million

Question 7

how many platelets made per second?

Answer 7

1 million

Question 8

broad causes of pancytopenia?

Answer 8

reduced production

increased destruction

Question 9

what can cause reduced production resulting in pancytopenia?

Answer 9

inherited syndromes
acquired causes (primary/secondary)

Question 10

characteristics of inherited marrow failure?

Answer 10

pre-disposition to cancer
impaired haemopoiesis
congenital anomalies
(all arise due to defects in DNA repair/ribosomes)

Question 11

give an examples of an inherited marrow failure syndrome

Answer 11

Fanconi’s anaemia

• short stature
• skin pigment anomalies
• radial ray abnormalities
• hypogenitalia
• endocrinopathies
• GI defects
• cardio problems
• renal
• haematological

Question 12

what skeletal and skin changes occur in marrow failure?

Answer 12

café au lait spots

skeletal abnormalities

Question 13

what causes the problem in inherited bone marrow failure?

Answer 13

unable to correct inter-strand cross-links (DNA damage)

Question 14

what haematological problems are associated with inherited bone marrow failure syndromes?

Answer 14

microcytosis followed by thrombocytopenia then neutropenia

Question 15

risk of bone marrow failure and leukaemia in inherited bone marrow failure syndromes?

Answer 15

84% risk of bone marrow failure by age 20

52% risk of leukaemia by age 40

Question 16

examples of primary acquired causes of reduced production resulting in pancytopenia?

Answer 16

idiopathic aplastic anaemia (autoimmune attack against haemopoietic stem cells)
myelodysplastic syndromes (MDS)
acute leukaemia

Question 17

pathogenesis of aplastic anaemia pathogenesis?

Answer 17

auto-reactive T cells attack haematopoietic stem cells and myeloid lineage precursors

Question 18

what happens in myelodysplastic syndromes?

Answer 18

dysplasia (disordered cell development)
hypercellular marrow
increased apoptosis of progenitor and mature cells (ineffective haemopoiesis)
has a propensity for evolution into AML

Question 19

how can acute leukaemia cause pancytopenia?

Answer 19

proliferation of abnormal cells (…blasts) from leukaemic stem cells
failure to differentiate or mature into normal cells
prevents normal haematopoietic stem cell/progenitor cell development by hijacking/altering the haematopoietic niche and marrow microenvironment

Question 20

secondary acquired causes of reduced production resulting in pancytopenia?

Answer 20

drugs (chemo, chloramphenicol, alcohol) can cause aplasia
B12/folate deficiency (causes problems with nuclear maturation and cell division in all lineages - causes hypercellular marrow)
infiltrative (non-haematopoietic malignant infiltration, lymphoma)
viral (HIV etc)
storage disease

Question 21

causes of increased destruction of cells resulting in pancytopenia?

Answer 21

hypersplenism

Question 22

what is found within parenchyma of spleen?

Answer 22

red pulp
- sinusoids and cords
white pulp

Question 23

features of sinusoids?

Answer 23

fenestrated
lined with endothelial cells
supported by hoops of reticulin

Question 24

features of cords?

Answer 24

contain macrophages, some fibroblasts, cells in transit (RBCs, WBCs) platelets and some CD8 T cells

Question 25

functions of spleen?

Answer 25

detect, retain and eliminate unwanted foreign/damaged material (including cells)
facilitates immune responses to blood borne antigens

Question 26

how does hypersplenism cause increased destruction of cells?

Answer 26

increased splenic pool

increased destruction that exceeds bone marrow capacity, usually associated with significantly enlarged spleen

Question 27

splenic red cell mass in normal/enlarged spleen?

Answer 27

normal = 5%
enlarged = 40%

Question 28

red cell transit in normal/enlarged spleen?

Answer 28

normal = fast
enlarged = slow

Question 29

splenic platelet pool in normal/enlarged spleen?

Answer 29

normal = 20-40%
enlarged = 90%

Question 30

causes of hypersplenism?

Answer 30

splenic congestion (portal hypertension, congestive cardiac failure)
systemic diseases (RA)
haematological diseases (splenic lymphoma)

Question 31

primary acquired reduced production?

Answer 31

idiopathic aplastic anaemia
myelodysplastic syndromes
acute leukaemias (bone marrow malignancy)

Question 32

secondary acquired reduced production?

Answer 32

drug induced aplasia
B12/folate deficiency
infections
metastatic cancer
storage disorders

Question 33

clinical features of pancytopenia can reflect what?

Answer 33

lack of circulating blood cells

the cause of the pancytopenia

Question 34

pancytopenia is a lack of what cells?

Answer 34

RBCs anaemia
neutrophils (neutrophils)
platelets (thrombocytopenia)

Question 35

investigations in establishing cause of pancytopenia?

Answer 35

history (including FH)
clinical findings
FBC and blood film
additional tests guided by above (B12, folate, LFT, virology, autoantibodies etc)
bone marrow examination
specialised tests

Question 36

types of bone marrow examination?

Answer 36

aspirate from posterior iliac crest
trephine biopsy (bone sample)

Question 37

how is bone marrow affected in pancytopenia?

Answer 37

aplastic anaemia = hypocellular
myelodysplastic syndromes = proliferation, apoptosis and hypercellular
B12/folate deficiency = late cell maturation failure, early proliferation, apoptosis and hypercellular)

Question 38

treatment of pancytopenia?

Answer 38

supportive

specific depending on cause

Question 39

types of supportive treatment in pancytopenia?

Answer 39

red cell transfusion
platelet transfusion
neutrophil transfusion (not routine)
antibiotic prophylaxis

Question 40

do you wait for microbiology results before antibiotics in neutropenic fever?

Answer 40

no

Question 41

specific treatment of primary bone marrow disorder?

Answer 41

malignancy = consider chemo
congenital = consider bone marrow transplant
idiopathic aplastic anaemia = immunosuppression

Question 42

specific treatment of secondary bone marrow disorder?

Answer 42

drug reaction = Stop the drug
viral = treat infection (eg HIV)
replace B12/folate

Question 43

specific treatment of hypersplenism?

Answer 43

treat cause if possible

consider splenomegaly