Question 26.1

The following data refer to a patient admitted to ICU with septic shock on a background of active rheumatoid arthritis.

Parameter

Patient Value

Adult Normal Range

Haemoglobin

86 g/L*

125 – 180

Serum ferritin

298 µg/L

15 – 300

Serum iron

7 µmol/L*

9 – 27

Total Iron Binding Capacity (TIBC)

52 µmol/L

47 – 70

Transferrin Saturation

(Iron / TIBC x 100)

28%

16 – 40

Erythropoietin level

15 U/L

4 – 28

C-reactive protein (CRP)

321 mg/L*

< 8

a)    State the abnormality demonstrated in this patient? Give your reasoning.    (20% marks)

b)    State the pathogenesis of these changes?    (20% marks)

c)    State the principles of management?    (10% marks)
 

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College answer

Very well answered, with most candidates demonstrating the ability to interpret and discuss anaemia. Many candidates omitted EPO and conservative treatment for iron-deficiency anaemia in the management part of the question. Poorer answers did not identify the cause of anaemia correctly.

Discussion

a)

So, this patient has

  • Anaemia
  • Sepsis
  • A raised CRP, suggestive of inflammation
  • Normal (perhaps slightly raised) ferritin, which makes sense because it is also an acute phase reactant
  • Low serum iron
  • Normal TIBC and transferrin saturation
  • Normal erythropoietin level (which is itself abnormal, because it should be raised in anaemia)

So: this is a classical picture seen with anaemia of inflammation. 

b)

The mechanism of this is as follows:

  • Decreased iron availability
    • Cytokine release in inflammation stimulates the synthesis of hepcidin, a regulatory molecule which controls the release of iron into the circulation.
    • A high hepcidin level decreases the availability of iron by promoting "iron trapping" within the bone marrow and macrophages. Thus, the iron stores in this form of anaemia are normal, which renders iron infusion pointless.
    • In the absence of circulating iron, erythropoiesis is restricted.
  • Increased erythrocyte phagocytosis
    • Cytokine-activated macrophages destroy red cells at an increased rate
    • This reduces the lifespan of erythrocytes.
  • Decreased erythropoiesis signals
    • Cytokines act directly on the bone marrow to reduce the rate of erythropoiesis, independent of the levels of circulating erythropoietin
    • Occasionally the level of erythropoietin is also suppressed, which is thought to be a cytokine-related effect acting on its renal secretion.

c)

Management consists of controlling the inflammation and transfusing red cells. Erythropoiesis will usually not respond to iron infusion (and anyway there's plenty of iron stores) and there is usually no added benefit from EPO.

References

Nemeth, Elizabeta, and Tomas Ganz. "Anemia of inflammation." Hematology/Oncology Clinics 28.4 (2014): 671-681.

Hawkins, Stephen F., and Quentin A. Hill. "Diagnostic Approach to Anaemia in Critical Care." Haematology in Critical Care: A Practical Handbook (2014): 1-8.