T3 L2&L3: Anaemia

• What is the definition of anaemia?

  when the haemoglobin (Hb) concentration falls below defined level (outside normal range)
• What are the clinical consequences and causes of anaemia?

  Clinical consequence of anaemia: insufficient delivery of oxygen to the tissues

  Causes:

  • decreased Hb content of red cells
  • decreased RBC numbers
  • altered Hb that does not carry sufficient O2
• What are some red cell indices?

  • Haematocrit / PCV: % of red cells after centrifugation
  • RBC: no of red cells per litre
  • MCV: mean cell volume
  • MCH: mean cell Hb
  • MCHC: mean cell Hb concentration

  
• Why is a blood film useful?

  easy and quick, can detect:

  • Haematinic deficiency:
  • Microcytic (small) / macrocytic (large); Hypochromic (pale); Anisopoikilocytosis (atypical size and shape)
  • Haemoglobinopathy:
  • sickled / target cells
  • Haemolysis:
  • Polychromasia (high reticulocytes)

  
• How does erythropoiesis work?

  hypoxia → kidneys → EPO → bone marrow → erythropoiesis → increased O2
• What is Bone marrow trephine?

  bone marrow biopsy

  
• What is Bone marrow aspirate?

  bone marrow biopsy

  
• What is the history like when anaemia is suspected?

  GI Symptoms: dyspepsia / reflux, change in bowel habit, weight loss

  Bowel history: Coeliac, Crohn's

  Menstrual history: menorrhagia (heavy bleeding)

  Any haematuria in urine (blood)
• What are the symptoms of anaemia?

  • lethargy, fatigue
  • exertional breathlessness
  • palpitations
  • headache
  • worse symptoms if acute onset
• What are the signs of anaemia?

  • skin pallor
  • pale conunctivae
  • tachypnoea
  • tachycardia
  • koilonychia (iron deficiency)

  
• What are the two main causes of anaemia?

  • Problems of red cell synthesis
  • Blood loss / over-consumption
• How can problems of inadequate red cell synthesis arise and cause anaemia?

  deficiency in haematinics (key component required for RBC formation)

  • Iron (iron-deficient anaemia)
  • B12 and folic acid (megaloblastic anaemia)

  Haemoglobinopathies: problems of Hb production (eg thalassemia)

  Bone marrow dysfunction / failure
• How can problems of excess destruction / loss of red cells arise and cause anaemia?

  Haemolysis / increased red cell destruction causing shortened RBC lifespan (haemolytic anaemias)

  Haemorrhage / blood sequestration
• How are anaemias classified?

  • Acute / Chronic: rapid fall / slow decline in Hb
  • Underlying aetiology: production / consumption problem
  • Size of red cell:
  • Microcytic (small)
  • Normocytic (normal)
  • Macrocytic (large)
• What are the causes of Microcytic red cells?

  iron deficiency

  inherited disorders of Hb (beta-thalassemia)
• What are the causes of Macrocytic red cells?

  B12 and folate deficiency

  Myelodysplasia (cancer)
• What are the two main causes of problems of red cell synthesis?

  Haematinic deficiency

  Inadequate red cell production - bone marrow failure
• What is iron deficiency?

  Most common cause of anaemia

  Causes:

  • chronic bleeding
  • nutritional deficiency
  • increased iron requirements

  Confirm with iron studies:

  • Ferritin (iron stores)
  • Serum iron (Fe)
  • Transferrin
  • Transferrin saturation %
• What is Serum Ferritin as a diagnostic test?

  storage form of iron

  low ferritin = iron deficiency

  high ferritin = iron overload (haemochromatosis - XS Fe gut absorption)
• What is Serum Iron as a diagnostic test?

  labile in blood

  reflects recent dietary intake of iron

  (hence unreliable)
• What is Serum Transferrin as a diagnostic test?

  protein that carries iron from gut to body stores

  iron deficiency → increased transferrin levels (homeostasis)

  sometimes measured as TIBC (total iron binding capacity)
• What is Transferrin Saturation % as a diagnostic test?

  sensitive measure of iron status

  reflects proportion of transferrin bound with iron

  low transferrin % = iron deficiency
• What are the causes of iron deficiency in the UK?

  Bleeding; GI, menstrual, renal tract

  Inadequate intake; dietary/malabsorption

  Increased requirements; pregnancy
• What are the investigation findings of Iron deficiency anaemia?

  Serum Iron: Low

  Transferrin / TIBC: high

  % Transferring saturation: Low

  Ferritin: low
• What are the investigation findings of Anaemia of Chronic Disease?

  Serum iron: Low / normal

  Transferrin / TIBC: Low / normal

  % Transferrin saturation: normal

  Ferritin: normal / high
• How is iron deficiency managed?

  1. Investigate and address underlying cause
  2. Treat with iron replacement (oral / IV)
• What is 'Anaemia of Chronic Disease'?

  caused by chronic inflammation

  often seen in hospitalised patients

  conditions such as malignancy, connective tissue disease, chronic infections

  Management: treat underlying cause
• What is microcytic hypochromic anaemia?

  pale small cells

  cause: iron deficiency

  blood film shows:

  • Pencil cells (elongated)
  • Target cells (bullseye appearance)

  
• What does this blood film show?

  Microcytic hypochromic anaemia in iron deficiency

  
• What are the causes of microcytic anaemia?

  Acquired: Iron deficiency

  • chronic bleeding (GI, menstrual)
  • Low ferritin
  • Low Fe, high transferrin, low tranferrin sat

  Inherited: Thalassaemia

  • haemoglobinopathy
  • usually beta-thalassaemia (causes alpha/beta globin imbalance)
  • normal ferritin, abnormal Hb electrophoresis
• What is beta thalassaemia?

  Haemoglobinopathy

  causes alpha/beta globin imbalance

  • β-thal trait = heterozygous carrier
  • β-thal major = homozygous disease

  causes microcytic anaemia

  • normal ferritin, abnormal Hb electrophoresis
• What is megaloblastic (macrocytic) anaemia?

  large red blood cells

  caused by:

  • Vitamin B12 deficiency
  • Folate deficiency
• What are megaloblastic features in bone marrow?

  oval macrocytes in peripheral blood

  hyperlobated neutrophils indicate myeloid right shift

  
• What does this blood film show?

  megaloblastic anaemia

  with macrocytic red cells

  and right-shifted hyperlobated neutrophils (more than 4 lobes)

  
• What are the causes of B12 deficiency?

  • Pernicious anaemia
  • Malabsorptive states: Crohn's, Coeliac
  • Surgical operations
  • Dietary

  Symptoms: beefy red tongue

  
• What is Pernicious Anaemia?

  autoimmune destruction of gastric parietal cells

  deficiency of IF required for B12 absorption

  cannot absorb B12 in terminal ileum

  Investigations:

  • IF antibodies
  • gastric parietal cell antibodies

  Treatment:

  • B12 injections
• What are the causes of Folate deficiency?

  • Dietary
  • Malabsorption
  • Excess utilisation
  • Alcohol
  • Anti-folate drugs

  Symptoms: aphthous ulcers
• What are some other causes of macrocytosis?

  • Alcohol
  • Liver disease
  • Pregnancy
  • Myelodysplasia
  • Cytotoxic drugs
  • Hypothyroidism
  • Reticulocytosis (polychromasia)
• What are the causes of normocytic anaemia?

  Anaemia of chronic disease

  Anaemia due to renal failure
• How can Anaemia of chronic disease cause normocytic anaemia?

  normal-sized cells

  iron trapped inside macrophages

  cancer, inflammation, rheumatoid arthritis

  normal/raised ferritin

  normal/low transferrin

  raised hepcidin (inflammatory protein)