Anaemia: Approach to Diagnosis Flashcards
(27 cards)
Definition of anaemia?
There are 2
Reduction in Hb conc. to the point that it is below the optimum for that individual
Reduction in Hb conc. to the point that it is below the 95% range for the population
Thresholds of Hb (g/L) for anaemia?
Children:
• 6 months to 6 years - 110 g/L
• 6-14 years - 120 g/L
Adults:
• Males - 130 g/L
• Females (non-pregnant) - 120 g/L
• Females (pregnant) - 110 g/L
NOTE - Hb tends to be fairly constant throughout life
Broad classifications of anaemia?
Decreased production:
• Hypoproliferative - reduced AMOUNT of erythropoiesis
• Maturation abnormality - erythropoiesis is present bur ineffective; this occurs with cytoplasmic defects (impaired haemoglobinisation) and nuclear defects (impaired cell division)
Increased loss or destruction of red cells:
• Bleeding
• Haemolysis
How will the reticulocyte count vary with the broad classifications of anaemia?
Decreased production -
e.g: hypoproliferative, maturation abnormalities; reduced reticulocyte count (inappropriate response)
Increased loss of destruction of red cells- e.g: haemolysis, blood loss - increased reticulocyte count (appropriate response)
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NOTE - unless there is an issue with the bone marrow, the reticulocyte count will increase in response to anaemia
What is the reticulocyte count a marker of?
Red cell production
Sign of haemolysis?
Reticulocytosis (an appropriate response to anaemia)
Anaemia
Increased products of red cell destruction (JAUNDICE):
• Increased unconjugated serum bilirubin
• Increased urinary urobilinogen
‘Work hypertrophy’ of macrophage-rich tissue, i.e: potentially a splenomegaly
NOTE - if a haemolytic anaemia is suspected, check for evidence of red cell breakdown products and a reticulocytosis; then consider a cause (blood film and history can help)
Products of red cell breakdown?
Globin - breakdown products are amino acids
Haem - breakdown products are:
• Porphyrin - degradation leads to bilirubin formation
• Iron - stored as ferritin or bound to transferrin for transport to marrow erythroblasts
Types of bilirubin?
Unconjugated (albumin-bound) - must go to the liver to be conjugated
Conjugated (glucoronides) - excreted as part of bile, into the gut; it is converted into either:
• Urobilinogen - excreted into the urine, via the kidneys
• Stercobilinogen - excreted into the faeces
NOTE - bilirubin is what provides colour to the urine and faeces
NOTE - in a conjugated hyperbilirubinaemia, the Hx may include dark urine and pale stools; as the cause is post-hepatic (obstructive), bilirubin does not enter the gut to be excreted into the faeces (become pale) and more is excreted as urobilinogen, into the urine (becomes dark)
Why does reduced reticulocyte count occur?
Anaemia with a lesser reticulocyte response is at least partly due to impaired red cell production
Classifications of anaemia based on MCV results?
Microcytic
Macrocytic
Normocytic
Classifications of anaemia based on blood film or MCH (surrogate marker for blood film results)?
Hypochromic
Normochromic
Most common cause of hypochromic microcytic anaemia?
Iron deficiency anaemia - consider the cause in each patient
NOTE - hypochromic and microcytic due to impaired Hb production
Other less common cause of microcytic anaemia?
Thalassaemia
Anaemia of chronic disease, e.g: chronic inflammation, malignancy
Lead poisoning
Pyridoxine responsive anaemias
Sideroblastic anaemia
Nutritional causes of a macrocytic anaemia?
Megaloblastic anaemia:
• Vitamin B12 deficiency
• Folate deficiency
NOTE - these patients often have a degree of pancytopaenia, as all cell division is affected
Other causes of macrocytic anaemia?
Myelodysplasia
Myeloma
Aplastic anaemia
Reticulocytosis
Cold agglutinins
Causes of a macrocytosis, often without anaemia?
Alcohol
Liver disease
Hypothyroidism
Causes of a normochronic normocytic anaemia?
Acute blood loss
Early iron deficiency (MCH may not fall until iron stores are exhausted)
Hypoproliferative (low reticulocyte count):
• ANAEMIA OF CHRONIC DISEASE, e.g: inflammatory, infective, malignant disorders
• Anaemia of renal failure
• Hypometabolic disorders, e.g: hypothyroidism
• Marrow failure, e.g: asplasia or infiltration
Why does anaemia occur with renal failure?
AKA renal anaemia (a type of anaemia of chronic disease)
Epo production decreases in most cases of renal failure
Why does Epo production not decrease in polycystic kidney disease?
Epo production is unaffected
What is anaemia of chronic disease?
Common cause of anaemia, second to iron deficiency
It has a multifactorial pathophysiology, with inflammation as the central process
NOTE - not all pathophysiological mechanisms occur in all cases
Most common cause of anaemia of chronic disease?
Inflammation - can cause anaemia via a no. of mechanisms:
- Inhibits Epo release
- Inhibits erythroid proliferation
- Augments haemophagocytosis
- Increases hepatic synthesis of hepcidin, which impairs iron availability to erythroid
This is driven by inflammatory cytokines
Function of hepcidin?
Inhibits iron release from the RES:
• Iron becomes trapped in macrophages and in hepatocytes
• Decreased intestinal iron absorption
Why do most chronic anaemias occur?
> 90% are primarily due to impaired red cell production (low reticulocyte count)
A few are due to haemolysis or acute bleeding (high reticulocyte count)
NOTE - >1 causative factor may occur, e.g: RA anaemia of chronic disease with NSAID-related GI blood loss; in this case, the iron deficiency limits erythroid marrow response to blood loss
How to use results to differentiate iron deficiency anaemia and anaemia of chronic disease?
Iron deficiency: • Serum iron - reduced • Transferrin - normal / increased • % transferrin saturation - reduced • Ferritin - reduced • MCV - reduced (can be normal)
Anaemia of chronic disease: • Serum iron - reduced • Transferrin - normal / reduced • % transferrin saturation - reduced • Ferritin - normal / increased • MCV - normal (can be reduced)
