Approach to Anaemia Diagnosis

Question 1

how is anaemia defined?

Answer 1

reduction in Hb concentration below that which is optimum for that individual (may need to look at previous Hb results)
in general, a Hb below 95% range for the population

Question 2

Hb concentrations below which anaemia is likely to be present?

Answer 2

children 6 months-6years = 110
6-14 years = 120
males = 130
females = 120
pregnant females = 110

Question 3

what tools can help diagnose anaemia?

Answer 3

history/examination/clinical context
FBC
reticulocyte count
blood film
haematinics (ferritin/B12/folate)
bone marrow biopsy
specialised tests (HbA2, HLPC etc)

Question 4

classification of anaemia?

Answer 4

decreased production vs increased loss/destruction of RBCs

Question 5

casues of decreased production?

Answer 5

hypoproliferative - reduced amount of erythropoiesis

maturation abnormality - erythropoiesis present but ineffective

Question 6

what can cause erythropoiesis to be ineffective?

Answer 6

cytoplasmic defects (impaired haemoglobinisation)
nuclear defects (impaired division)

Question 7

what can cause increased loss/destruction of RBCs?

Answer 7

bleeding

haemolysis

Question 8

why is reticulocyte count useful?

Answer 8

marker of RBC production
increased RBC production = regenerative anaemia
lots of reticulocytes means the bone marrow is producing lots of immature RBCs very quickly to try and compensate

Question 9

anaemia with increased reticulocytes indicates what as a cause?

Answer 9

haemolysis or blood loss

Question 10

reduced reticulocyte response (anaemia without reticulocytosis) indicates what as a cause?

Answer 10

abnormal maturation of RBCs or hypoproliferative anaemia

Question 11

how will RBCs appear in abnormal maturation of RBCs vs hypoproliferation of RBCs?

Answer 11

abnormal maturation = microcytic hypochromatic or macrocytic normochromatic

hypoproliferation = normocytic normochromatic (RBCs are normal just not enough)

Question 12

what to look for if reticulocytosis is seen?

Answer 12

RBC breakdown products
haemolysis = products of RBC destruction are seen
bleeding = red cells are gone (nothing to breakdown)

Question 13

what products of RBC breakdown might be seen in haemolysis?

Answer 13

increased unconjugated serum bilirubin

increased urinary urobilinogen

Question 14

what do you look for if haemolytic anaemia is suspected?

Answer 14

evidence of RBC breakdown products and reticulocytosis

Question 15

relativity of reticulocyte response?

Answer 15

reticulocyte count should be appropriately increased for the degree of anaemia
anaemia with a lesser reticulocyte response is at least partly due to impaired RBC production

Question 16

how much can normal marrow increase RBC count?

Answer 16

3-4 fold

Question 17

MCH?

Answer 17

mean cell haemoglobin

Question 18

what causes hypochromic microcytic anaemia?

Answer 18

problems with Hb production (cell just keeps dividing without filling with Hb)
can be due to
- iron deficiency
- heme defects (lead poisoning, songenital sideroblastic anaemia)
globin defects (thalassaemias)
(can rarely be due to anaemia of chronic disease)

Question 19

what causes macrocytic anaemia?

Answer 19

nuclear maturation defects (failure of cell division)

• nutritional (B12/folate) = megaloblastic anaemia
• myelodysplasia
• drugs (e.g chemotherapy)

Question 20

what can cause apparent macrocytic anaemia (not really macrocytic just looks like it)?

Answer 20

agglutination (cells stucj together are counted as 1 large cell)
reticulocytosis (presence of large reticulocytes in blood raises mean cell volume)

Question 21

what can cause microcytosis without significant anaemia?

Answer 21

hypothyroid
alcohol
liver disease

Question 22

what can cause normochromic normocytic anaemia?

Answer 22

hypoproliferative

• marrow failure (drug induced, anaplastic anaemia)
• hypometabolic
• marrow infiltration (metastatic malignancy, fibrosis)
• renal impairment
• chronic disease (infection, inflammation, malignancy)

Question 23

what is renal anaemia?

Answer 23

an anaemia of chronic disease due to failure of erythropoietin production
kidneys detect reduced O2 carrying capacity of blood > secrete erythropoietin in response to hypoxia > erythropoietin stimulates RBC production in marrow > additional circulating erythrocytes increase O2 carrying capacity of blood > increased O2 carrying capacity relieves initial stimulus that triggered erythropoietin secretion

Question 24

what is anaemia of chronic disease?

Answer 24

multifactorial pathophysiology with inflammation being the central process
2nd most common cause of anaemia

Question 25

how does anaemia of chronic disease occur?

Answer 25

chronic inflammatory stimulus> activation of monocytes and T cells >

• increases hepatic synthesis of hepcidin (inhibits iron release from cells)
• inhibits erythropoietin release from kidney
• inhibits erythroid proliferation in bone
• augments hemophagocytosis

Question 26

anaemia of chronic disease summary?

Answer 26

driven by inflammatory cytokines induced by infection/malignancy/autoimmune disease
causes blunted EPO response by kidney
impaired iron availability to erythroid precursors
inhibition of proliferation
reduced RBC survival

Question 27

why can anaemia of chronic disease sometimes be microcytic?

Answer 27

if the predominant mechanism is through hepcidin stimulation

• may be microcytic due to reduced release of iron from macrophages (i.e failure of Hb synthesis)
• explains low transferrin saturation despite normal/raised ferritin
• explains why it may respond to IV iron

Question 28

most anaemias are which type?

Answer 28

hypoproliferative

therefore don’t usually do reticulocyte count unless haemolysis is suspected

Question 29

how is MCV used in anaemia?

Answer 29

should be relative to the patient
microcytosis can be relative rather than absolute, so many iron deficient patients actually have a normal range MCV although its abnormal for the individual

Question 30

often more than one factor is present causing anaemia, give an example of this

Answer 30

rheumatoid arthritis patient (anaemia of chronic disease) on methotrexate (folate antagonist) with occult GI blood loss 2ndary to NSAID gastropathy (iron deficiency)

Question 31

iron deficiency vs anaemia of chronic disease?

Answer 31

serum iron reduced in both
transferrin
- normal/increased in iron, normal/decreased in AOCD
% transferrin saturation
- reduced in both
ferritin
- reduced in iron, normal/increased in AOCD
MCV
- reduced (can be normal) in iron, normal (can be reduced) in AOCD

Question 32

commonest cause of microcytic anaemia?

Answer 32

iron deficiency
can be thalassaemia
- major if severely low Hb
- trait if mild anaemia

Question 33

what does a very high ferritin indicate?

Answer 33

inflammatory response