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 |
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) What abnormality is demonstrated in this patient? Give your reasoning. (20% marks)
b) What is the pathogenesis of these changes? (20% marks)
c) What are the principles of management? (10% marks)
This question is essentially identical to Question 18.1 from the first paper of 2015, except in the older SAQ question (c) reads "what specific treatment strategy would correct the demonstrated abnormality" instead of "what are the principles of management". These two alternative wordings must surely mean the exact same thing, because the college answer was identical for both versions of the question.
Anyway: a generic iron studies interpretation rubrik looks like this:
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The college answer refers to "Anaemia of Inflammation", a nomenclature which has superseded "anaemia of chronic disease" as the description of the anaemia which has low serum iron in spite of normal body iron stores (i.e. normal ferritin).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.
The erythropoietin level is a weird thing to add because it is expensive and not usually a part of the normal panel. The RPCA Manual lists it as one of the tests "occasionally indicated" to discriminate primary from secondary erythrocytosis. It is not essential to the diagnosis of anaemia.
The mechanism of anaemia of inflammation can be summarised as follows:
Routine management of such an anaemia is therefore somewhat unexciting:
But let's say that for some reason you've lost interest in treating causes of things. Can we cosmetically make the iron study numbers look better? Turns out that yes, we can. There are several possible treatments for this sort of anaemia which specifically target the mechanism of its pathogenesis:
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.
Nemeth, Elizabeta, and Tomas Ganz. "Anemia of inflammation." Hematology/Oncology Clinics 28.4 (2014): 671-681.