Investigations of Anaemia Flashcards
DDx of Microcytic Anaemia
Iron Deficiency
Thalassemia
Sideroblastic anaemia
Iron Deficiency Anaemia
Must identify cause of iron deficiency!
- chronic blood loss e.g. GI occult bleed, menorrhagia
- reduced absorption (uncommon) e.g. duodenal disease, drugs affecting duodenum, acidic env. + Vitamin C needed for Fe absorption
Stages of deficiency
- iron depletion – use up storage, normal functional levels remain
- iron deficiency erythropoiesis – exceeds store and uses functional Fe
- iron deficiency anaemia – problem in generating red cells
Recall Iron metabolism
Transferrin – transport iron in plasma and extracellular fluids
Transferrin receptor – present on cell membranes, internalises transferring to acquire intracellular iron
Ferritin
- store in intestinal mucosal cells after absorption = retained and lost as cells are sloughed off
- stores iron in tissues
Hepcidin
- key negative regulator of intestinal iron absorption and macrophage iron release in response to increased iron levels (blocks iron supply to plasma)
Evaluation of Iron Deficiency
- reduced/ absent storage
- increased transport capacity to facilitate iron uptake and transport to RBC precursors in BM
Iron profile:
- serum Fe
- serum ferritin
- serum transferrin/ total iron binding capacity
- iron saturation
Serum Iron
Low in iron deficiency (and also anaemia of chronic disease)
Fluctuations with dietary intake, normal diurnal variation, menstrual cycle, oral contraceptives –> not a good indicator of iron storage
NOT DIAGNOSTIC of iron deficiency
Serum Ferritin
Circulating iron storage protein which is increased proportion to body iron stores
LOW LEVELS DIAGNOSTIC of iron deficiency
Also an acute phase reactant
- increase independently of iron status
- inflammation, infection, malignancy
- “false normal” results
Serum Transferrin
Circulating transport protein for iron; may be reported as TIBC
Increase in iron deficiency
Decreased or normal in anaemia of chronic disease
Iron Saturation
Ratio of serum iron to TIBC
Low saturation in iron deficiency
Anaemia of Chronic Disease
E.g. malignancy, infections
Normocytic, normochromic/ hypochoromic anaemia
Immune-mediated (may increase hepcidin)
Disturbance of iron homeostasis with increased uptake and retention of iron within cells of reticuloendothelial system –> can’t release/use –> limited availability of iron for RBC precursor cells
Iron profile:
- low serum iron and iron saturation
- normal/high serum ferritin
- reduced/normal serum transferrin
Iron profile to distinguish Fe deficiency and Chronic disease
Anaemia of Chronic Disease
- low/normal transferrin
- normal/high ferritin
Fe deficiency
- high transferrin
- low ferritin
Both conditions e.g. rectal cancer causing chronic blood loss
- no clear iron profile
- low transferrin (long duration of chronic disease leads to intrinsic reduction of transport capacity in body – can’t increase in response to Fe deficiency)
- low/normal ferritin
Iron overload
Highly toxic (not a cause of anaemia!)
Causes:
- intake (rare)
- increased absorption e.g. hereditary haemochromatosis (usually increased ferritin and TIBC is first to change)
- repeated transfusion (major cause) e.g. thalassemia major (despite iron chelation)
Lab
- high serum ferritin
Toxic effects (deposition) - liver (cirrhosis), pancreas (DM), testis (hypogonadism), heart (cardiomyopathy), skin (dark grey discolouration), joint (arthropathy)
DDx of macrocytic anaemia
Megaloblastic anaemia
- vitamin B12/ folate deficiency
Other causes:
- hypothyroidism
- alcohol
- liver disease
- myelodysplastic syndrome
- aplastic anaemia
Megaloblastic anaemia
Delayed maturation of nucleus relative to cytoplasm of erythroblast –> resulting in defective DNA synthesis
Lab assessment - serum vitamin B12 - serum folate - auto-Ab to IF \+/- red cell folate (surrogate for tissue folate levels)
Functions of B12 and Folate
B12 (methylcobalamin) required in the conversion of methyltetrahydrofolate to THF which are the building blocks of DNA
Folate from plasma is received as methyl THF
Folate source and deficiency causes
Unable to synthesis folates in our body
- obtained from diet e.g. green veg, meat
- required for DNA and RNA synthesis
Causes of deficiency
- nutritional poor intake
- malabsorption
- increased demand e.g. pregnancy, haemolytic anaemia, myelofibrosis
- drugs e.g. methotrexate (folate antagonist), phenytoin (also acts like folate antagonist)
