The following data refer to a 65-year-old male admitted to ICU with septic shock on a background of active rheumatoid arthritis.

Parameter Patient Value Normal Adult 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) What abnormality is demonstrated in this patient? Give your reasoning. (20% marks)

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

c)  What specific treatment strategy would correct the demonstrated abnormality? (10% marks)

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College Answer

a)

Anaemia of Inflammation demonstrated by:

  • decreased haemoglobin
  • decreased iron
  • normal to high ferritin
  • suppressed erythropoietin
  • elevated CRP
 
 

b)

Inflammation -> cytokines (IL6) -> increased hepcidin -> decreased iron release from bone marrow, decreased iron release from macrophages, decreased absorption of iron -> suppressed erythopoeisis

c)

Control inflammation, no value to iron replacement, no value to the use of erythropoietin.

Discussion

Local resources to help with such questions include the following chapters:

In the above, there is a table of typical findings which is reproduced below:

Interpretation of Abnormal Iron Studies
Condition MCV MCHC Serum iron Ferritin Transferrin Transferrin
saturation
TIBC
Iron deficiency anaemia low low low low high <20% high
Anaemia of inflammation (chronic disease) low low low normal low normal low or normal
Acute phase response normal normal low high low low low
Iron overload normal normal high high normal high high

The college answer refers to "Anaemia of Inflammation", a nomenclature which has superseded "anaemia of chronic disease" as  the description of the anaemia which has low serum iron in spite of normal body iron stores (i.e. normal ferritin). This "inflammation" could actually be anything proinflammatory, and so it would be difficult to comment whether the rheumatoid arthritis is more responsible then the sepsis, or vice versa. In either case, the biochemical picture would be more or less the same.

Alternative explanations for these laboratory results could also include the anaemia of decreased erythropoietin release associated with renal failure; but the college specifically gave us RA, sepsis and a raised CRP, clearly aiming the candidates at something inflammatory. Iron studies in anaemia of chronic renal failure tend to demonstrate iron deficiency, i.e. the ferritin is also low, but there is a group in whom there is a "functional" iron deficiency with normal ferritin levels and a failure of iron release from body stores (Babitt & Lyn, 2012). If the inflammatory elements were omitted from the story, this would be a legitimate alternative explanation

References

References

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

Gross, I. "Laboratory Studies in the Diagnosis of Iron Deficiency, Latent Iron Deficiency and Iron Deficient Erythropoiesis". from http://iron.sabm.org

Pieracci, Fredric M., et al. "A Multicenter, Randomized Clinical Trial of IV Iron Supplementation for Anemia of Traumatic Critical Illness*." Critical care medicine 42.9 (2014): 2048-2057.

Litton, Edward, et al. "The IRONMAN trial: a protocol for a multicentre randomised placebo-controlled trial of intravenous iron in intensive care unit patients with anaemia." Crit Care Resusc 16 (2014): 285-290.

Corwin, Howard L., et al. "Efficacy of recombinant human erythropoietin in critically ill patients: a randomized controlled trial." Jama 288.22 (2002): 2827-2835.

Mesgarpour, Bita, et al. "Safety of off-label erythropoiesis stimulating agents in critically ill patients: a meta-analysis." Intensive care medicine 39.11 (2013): 1896-1908.

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

Babitt, Jodie L., and Herbert Y. Lin. "Mechanisms of anemia in CKD." Journal of the American Society of Nephrology (2012): ASN-2011111078.