Approach to Anaemia Diagnosis Flashcards
how is anaemia defined?
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
Hb concentrations below which anaemia is likely to be present?
children 6 months-6years = 110 6-14 years = 120 males = 130 females = 120 pregnant females = 110
what tools can help diagnose anaemia?
history/examination/clinical context FBC reticulocyte count blood film haematinics (ferritin/B12/folate) bone marrow biopsy specialised tests (HbA2, HLPC etc)
classification of anaemia?
decreased production vs increased loss/destruction of RBCs
casues of decreased production?
hypoproliferative - reduced amount of erythropoiesis
maturation abnormality - erythropoiesis present but ineffective
what can cause erythropoiesis to be ineffective?
cytoplasmic defects (impaired haemoglobinisation) nuclear defects (impaired division)
what can cause increased loss/destruction of RBCs?
bleeding
haemolysis
why is reticulocyte count useful?
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
anaemia with increased reticulocytes indicates what as a cause?
haemolysis or blood loss
reduced reticulocyte response (anaemia without reticulocytosis) indicates what as a cause?
abnormal maturation of RBCs or hypoproliferative anaemia
how will RBCs appear in abnormal maturation of RBCs vs hypoproliferation of RBCs?
abnormal maturation = microcytic hypochromatic or macrocytic normochromatic
hypoproliferation = normocytic normochromatic (RBCs are normal just not enough)
what to look for if reticulocytosis is seen?
RBC breakdown products
haemolysis = products of RBC destruction are seen
bleeding = red cells are gone (nothing to breakdown)
what products of RBC breakdown might be seen in haemolysis?
increased unconjugated serum bilirubin
increased urinary urobilinogen
what do you look for if haemolytic anaemia is suspected?
evidence of RBC breakdown products and reticulocytosis
relativity of reticulocyte response?
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
how much can normal marrow increase RBC count?
3-4 fold
MCH?
mean cell haemoglobin
what causes hypochromic microcytic anaemia?
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)
what causes macrocytic anaemia?
nuclear maturation defects (failure of cell division)
- nutritional (B12/folate) = megaloblastic anaemia
- myelodysplasia
- drugs (e.g chemotherapy)
what can cause apparent macrocytic anaemia (not really macrocytic just looks like it)?
agglutination (cells stucj together are counted as 1 large cell)
reticulocytosis (presence of large reticulocytes in blood raises mean cell volume)
what can cause microcytosis without significant anaemia?
hypothyroid
alcohol
liver disease
what can cause normochromic normocytic anaemia?
hypoproliferative
- marrow failure (drug induced, anaplastic anaemia)
- hypometabolic
- marrow infiltration (metastatic malignancy, fibrosis)
- renal impairment
- chronic disease (infection, inflammation, malignancy)
what is renal anaemia?
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
what is anaemia of chronic disease?
multifactorial pathophysiology with inflammation being the central process
2nd most common cause of anaemia
how does anaemia of chronic disease occur?
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
anaemia of chronic disease summary?
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
why can anaemia of chronic disease sometimes be microcytic?
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
most anaemias are which type?
hypoproliferative
therefore don’t usually do reticulocyte count unless haemolysis is suspected
how is MCV used in anaemia?
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
often more than one factor is present causing anaemia, give an example of this
rheumatoid arthritis patient (anaemia of chronic disease) on methotrexate (folate antagonist) with occult GI blood loss 2ndary to NSAID gastropathy (iron deficiency)
iron deficiency vs anaemia of chronic disease?
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
commonest cause of microcytic anaemia?
iron deficiency
can be thalassaemia
- major if severely low Hb
- trait if mild anaemia
what does a very high ferritin indicate?
inflammatory response
