Interpretation of Lab Tests Anaemia

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Interpretation of Lab TestsAnaemia
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Case One

• 18 year female
• Medical history unremarkable
• Nil regular medications
• Smokes 25 cigs/day
• Etoh binge drinking 2-3 / week

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Social background

• Lives with family
• partner
• no children
• unemployed

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Presenting complaint

• Syncopal episode after shower
• 6/12 lethargy
• 2/52 dyspnoea
• 6/12 LOW 6 kg

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• No night sweats/fevers
• no change bowel habit
• no haematuria /haemoptysis
• menorrhagia
• 3/52 cycle
• menstruating 7-14 days
• heavy

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Examination

• pale conjunctiva
• P100
• BP100/60
• PSM LSE
• rest unremarkable

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Blood Results
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Management

• Transfusion 4 units PC slowly
• Iron supplementation
• Gynaecological review
• Regular outpatient review

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Microcytic anaemia

• Iron deficiency
• Chronic disease
• Thalassaemia trait
• Sideroblastic anaemia

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Diagnosis

• RBC indices
• Haematinics
• Blood film
• Bone marrow

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Anaemia

• Reduction in O2 transport capacity of blood
• Reduction in red cell mass
• volume of packed red cells- Haematocrit
• Reduction in Hb concentration of blood
• Hb concentration blood lt13.5 g /dl males
• lt11.5 g/dl females

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Indices

• HCT- volume of packed red cells
• MCV -mean cell volume, average volume of a rbc
• MCH- mean cell Hb, average mass of Hb per red
  cell
• MCHC - average conc of Hb in a given volume of
  packed red cells

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• Ferritin- primary iron storage protein
• plasma ferritin indicator of body iron stores
• Transferrin- glycoprotein, transports iron
• normal 33 saturation with iron
• Immature red cells have high affinity receptors
  for transferrin

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Microcytic /Hypochromic

• MCV lt80 fl femtoliters, cubic micrometer
• MCH lt 27 pg picogram
• fall prior to development of anaemia

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Iron studies

• Ferritin 15 - 300 ug/l
• hepatic and macrophage iron stores
• lt15 ug/l specific for storage iron depletion
• normal value does not exclude depletion
• Why?
• Acute phase reactant, synth incr inflammation
• Released with damage to ferritin rich tissue

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Deficient iron supply to tissues

• Low serum iron
• Low serum transferrin saturation
• lt 15 unable to support erythropoeisis
• Rise in TIBC (reflecting transferrin
  concentration)

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Serum transferrin receptors

• Impaired iron supply,leads to increased cellular
  expression of transferrin receptors
• increased cell bound receptors and soluble forms,
  circulating in blood
• Level of soluble transferrin receptor inversely
  related to available serum iron

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Sequence of events

• 1 Depletion of iron stores
• low ferritin
• 2 Iron deficient erythropoiesis
• low iron, low transferrin saturation, rise in
  transferrin, increased serum transferrin Rc
• MCV and MCH may be normal
• 3 Iron deficiency anaemia
• MCV and MCH reduced,TIBC rises
• low reticulocyte count

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Blood Film- Iron deficiency

• Hypochromic (paler)
• microcytic (smaller)
• occasional targets
• poikilocytosis, pencil, tear drop
• anisocytosis

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Bone marrow Iron stain
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Cause of Iron deficiency MUST be investigated
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Case 2

• 80 years old man
• Chronic renal failure
• pneumonia

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Anaemia of Chronic disorders

• Reduced erythroid proliferation
• impaired utilization of iron in macrophage stores
• reduced tissue iron supply
• normal or raised ferritin
• reduced TIBC
• normal serum transferrin receptor

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Thalasaemia

• Microcytosis gtgt hypochromasia
• MCHC usually normal
• RBC size more uniform
• Target cells and basophilic stippling more
  prominent
• serum iron increased or normal

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Case 3

• 33 years old lady
• Italian
• Family history of Thalasaemia, requiring blood
  transfusion

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Case 4

• 50 years old man
• Paediatrician
• No regular medications

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Presenting complaint

• 9/12 lethargy
• 10 kg weight loss
• Depressed
• Difficulty coping at work

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Examination

• Flat affect
• Pale

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Blood tests
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Diagnosis

• Vitamin B12 deficiency

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Treatment

• Vitamin B12 supplementation

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Megaloblastic Anaemia

• MCV gt 95 fl
• Causes
• Vitamin B12 deficiency
• Folic acid deficiency
• alcohol
• liver disease
• myelodysplasia / aplastic anaemia
• Hydroxyurea /antifolate drugs

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Impaired DNA synthesis

• B12 /folic acid, coenzymes in DNA synth
• defective nuclear maturation
• asynchrony between nuclear and cytoplasmic
  maturation
• ineffective granulopoiesis, and thrombopoiesis
  gtgtpancytopenia

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Blood film

• Anisocytosis - macro ovalocytes
• normochromic
• neutrophils larger than nomal and hypersegmented
• leukopenia / thrombocytopenia

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Megaloblastic anaemia

• Investigation - family history, general medical
  history, dietary history and history of current
  drug intake.
• Laboratory tests - assays of serum vitamin B12
  and red cell folate.

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Red cell folate

• more informative than serum folate.
• Red cell folate reflects the body's stores of
  folate when the red cells were produced whereas
  serum folate reflects only recent folate intake
  and absorption

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Schilling Test

• Pernicious Anaemia- ST shows reduced absorption
  of oral vitamin B12 that is corrected if the
  test is repeated with the addition of oral
  intrinsic factor.
• small bowel B12 malabsorption there is no
  correction.

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Antibodies

• Testing for antibodies to gastric parietal cells
  is a sensitive (90) test for pernicious anaemia
  but is lacking in specificity.
• Intrinsic factor antibodies has much better
  specificity although sensitivity (50) is
  considerably less.

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Case 5

• 30 year female
• 1/12 weakness, lethargy
• 2/52 progressive icterus
• 2/52 dyspnoea on exertion
• Otherwise well
• No regular medications

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• No history recent viral infections
• No fevers/ night sweats
• No new medications/antibiotics
• No horticultural pursuits or industrial exposures
• Family history not significant

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Examination

• Afebrile
• P 110
• Jaundiced
• No sign infection
• Abdominal exam, mild splenomegaly

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Blood Tests
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Treatment

• Prednisone 1mg/kg
• Folic acid 5 mg /day
• Gradual tapering of prednisone over coming weeks

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Haemolysis

• Shortened survival of RBCs lt100 days
• Causes
• Intracorpuscular
• Extracorpuscular
• Sites
• Intravascular
• Extravascular

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Abnormal RBC

• Intracorpuscular
• unstable Hb to oxidative challenge
• RBC membrane abnormalities
• Thalassaemia
• Congenital Spherocytosis
• RBC enzyme abnormality
• Pyruvate Kinase deficiency
• G6PD deficiency

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Normal RBC

• Extracorpuscular
• Ab against RBC membrane,
• Autoimmune HA, cold and warm
• Trapping of RBC, splenomegaly
• Trauma ,high flow jets or fibrin strands
• cardiac valves, DIC
• exposure to oxidative stress
• Invasion of RBCs, malaria

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Sites of Destruction

• Intravascular
• severe RBC destruction
• immediate lysis in intravascular space
• Extravascular
• less severe RBC damage
• cells destroyed in monocyte /macrophage RE
  system, spleen,liver, bone marrow and lymph nodes

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Diagnosis of Haemolysis

• Two major tests
• Serum Lactate Dehydrogenase - high
• released from haemolyzed RBCs
• Haptoglobin - low
• protein capable of binding Hb
• binds free Hb in intravascular haemolysis
• incomplete phagocytosis during extravascular
  haemolysis

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Reticulocyte count

• Normal is 0.5 to 1.5
• anaemia causes increased erythropoietin,
  stimulates erythropoiesis
• increased retic count and percent
• ( gt4 to 5 )

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Other tests

• Increased serum indirect bilirubin - due to
  catabolism of Hb, production of biliverdin
• Increased MCHC - due to prescence of spherocytes
• Coombs test, positive direct antiglobulin test in
  autoimmune HA
• monoclonal Ab against IgG and C3d

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• If symptoms related to cold
• cold agglutinins
• Donath-Landsteiner Ab

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Additional tests for Intravascular Haemolysis

• Haemoglobinaemia- plasma Hb conc (haptoglobin
  saturated by released free Hb)
• Haemoglobinuria (free Hb saturates renal tubular
  resorptive capacity)
• Testing for Haemosiderin in shed tubular cells, 7
  days later

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Acute intravascular haemolysis

• Urine sample compared with a normal urine sample.
  Haemolysis of this severity is seen in
  'blackwater fever' associated with malaria.

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Other tests, cont

• Methaemalbuminaemia - Schumms test
• Free Hb, removed by hepatic macrophages
• is oxidized to metHb and released from cell
• binds to plasma albumin forming methaemalbumin
• Detected spectrophotometrically

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Blood film in Haemolysis

• Damaged red cells
• spherocytes, microsperocytes, elliptocytes
• Reticulocytes
• large polychromatic cells
• Fragmented RBCs- microangiopathic HA
• schistocytes, helmet cells
• Blister /bite cells of oxidative haemolysis

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Blood Film HA