List the potential  causes of anaemia  in critically ill patients,  and outline how you would determine which factors were contributory.

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College Answer

Common problems encountered related to the lack of an organised approach (eg. to history, examination and investigation). Blood loss can be occult!

Anaemia in critically ill patients is usually multifactorial. Potential causes can be categorised into decreased production (as a small proportion [approx 1%] of circulating RBCs are destroyed each day), increased destruction, loss of RBCs and haemodilution. Decreased production includes problems with nutrients (eg. iron, folate, B12), disease involving bone marrow (eg. infiltration, myelodysplasia), depressant effects of drugs (eg. chemotherapy) or irradiation, and low levels of stimulatory hormones (eg. EPO in renal failure, thyroid hormones). Increased destruction can occur in haemolytic anaemias: either congenital (eg. thalassaemia major, sickle cell) or acquired (eg. Coomb’s positive auto-immune, TTP-HUS, infection with malaria or clostridiae etc). Increased RBC loss can occur via injuries, bleeds into viscera or organs (eg. GI tract, GU tract, lungs) and iatrogenic (procedures, blood samples for testing). Dilutional anaemia usually occurs in the context of rapid or extensive non-blood fluid resuscitation.

Evaluation of cause includes obvious but essential role of history (trauma, drugs and therapies, nutrition, chronic disease, infection, review of blood tests and procedures etc) and examination (trauma, sites of potential blood loss [including PR], jaundice, hepato-splenomegaly etc.). Simple investigations include morphological assessment of blood (eg. MCV, blood film: red and white cell mophology), reticulocyte count, electrolytes and renal and liver function tests. More specific tests
as indicated include assays for folate/B12/ferritin, indicators of haemolysis (eg. haptoglobin, Coomb’s test), Hb electropheresis, cultures for infection (±thick/thin film) etc.

Important causes in ICU, which the candidate should emphasise, include:
a)  blood samples for testing
b)  EPO suppression and lack of marrow responsiveness in sepsis c)  trauma
d)  stress ulcer bleeds
e)  extracorporeal circuits blood loss

f)      hemodilution from resuscitation

g)  chemo/oncology patient groups


This question is best approached systematically. For this purpose, anaemia can be divided into groups by function (rather than the conventional classification, by RBC morphology - into normocytic, microcytic and macrocytic).

The conventional approach is by far the better approach, because with the low haemoglobin result one usually also gets a whole panel of RBC volume and Hb content indices, which immediately allows one to classify the anaemia into groups. The Mayo Clinic Proceedings have an excellent article from 2003 which does this topic justice.

Dilution of RBC concentration

  • dilutuonal anaemia with fluid replacement
  • Artifactual anaemia due to sampling of a vessel with diluted content (i.e. the vein that has the fluids running through it).

Increased loss of RBCs

  • Extravascular loss
    • Bleeding:
      • Traumatic blood loss
      • Upper or lower GI blood loss, eg. gastric erosion/ulceration
      • Iatrogenic loss through samling and surgery
  • Intravascular loss
    • Intravascular haemolysis, eg. autoimmune hemolytic anaemia
    • DIC
    • Mechanical haemolysis, eg. due to extravascular perfusion circuits, dialysis filters, or mechanical heart valves
    • Appropriate reticuloendothelial sequestration of abnormal haemoglobin
      • Thalassaemias
      • Methaemoglobinaemia
      • Sickle cell anaemia

Decreased production of RBCs

  • Decreased hematinics
    • B12/folate deficiency
    • Drugs which interfere with B12/folate metabolism
    • Iron deficiency
  • Decreased proliferation signals
    • Decreased EPO in renal failure
    • Anaemia of chronic inflammatory states

Thus, a panel of investigations which might differentiate between the abovementioned differentials should include the following:

  • History of fluid resusictation or trauma
  • Resampling to confirm the diagnosis
  • Imaging to look for obvious blood loss
  • Faecal occult blood test and/or endoscopy to exclude GI blood loss
  • Direct Coombs test, formal blood film, conjugated/unconjugated bilirubin, LDH, haptoglobin and reticulocyte count to investigate haemolysis
  • RBC folate and B12 levels
  • Iron studies
  • Coagulation screen (looking for DIC and MAHA)
  • Renal function tests and/or EPO levels


Walsh, T. S. "Anaemia during critical illness." British journal of anaesthesia97.3 (2006): 278-291.


Vincent, Jean Louis, et al. "Anemia and blood transfusion in critically ill patients." Jama 288.12 (2002): 1499-1507.


Tefferi, Ayalew. "Anemia in adults: a contemporary approach to diagnosis."Mayo Clinic Proceedings. Vol. 78. No. 10. Elsevier, 2003.