First Things First

• Essentially an anemia of acute, pro-inflammatory illness not related to hemorrhage, but associated with infection/inflammation
• Distinguishing the anemia of acute inflammation in critical illness (AAICI) from iron deficiency anemia (IDA) can be difficult because of the resultant physiology of iron metabolism in illness.
  • They often coincide.
  • Pts who present with IDA as the diagnosis by default have lost physiologic reserve and have decompensated. This decompensation leads to a mixed picture of anemia and to the complexity of a straightforward diagnosis or prognosis.
• The human body attempts to protect itself by sequestering substrates from pathogenic organisms.
• The illness itself can cause low-level hemolysis, DIC.
• Try to tease out the difference so that underlying disease states do not remain elusive, ultimately worsening outcome.
• Rule out acute blood loss anemia, which may not be associated with a low-iron state initially.
• Key features are anemia similar to chronic illness and IDA combined, with elevated fibrinogen levels, low to low-normal iron, high ferritin, low TIBC.
• Hepcidin and pro-inflammatory cytokine related (macrophage, IL-1, IL-6)
• Sepsis and other inflammatory disorders induce TNF-α, which stimulates macrophages responsible for IL-6.
• IL-6 induces production of hepcidin, an iron-regulatory hormone responsible for the aspects of this disorder:
  • Inflammation leads to macrophage elaboration of IL-6, which acts on hepatocytes to induce hepcidin production.
  • Hepcidin inhibits macrophage iron release and intestinal iron absorption.
  • Inadequate RBC production secondary to poor substrate metabolism, poor iron delivery to marrow, and utilization
  • Reduced erythropoietin and RBC life span
• Look for occult sources of blood loss (see Anemia).
• Patients who have IDA usually have a continuous occult bleed, malignancy or myeloaffective disorder rendering them more susceptible to illness.
• Blood loss, SIRS/sepsis, and medications are the most common cause of AAICI.
• Hemolysis, as a component of blood loss and inflammation, often accompanies both.
  • Doesn’t have to be blood loss itself—anything that reduces blood counts, increases demands or affects iron metabolism can lead to IDA, AAICI or both.
• Iron-deficient RBC production is evident in up to 35% of critically ill patients at admission.
• Prolongs LOS in ICU, but treatment options often cause risks that increase LOS
• Dramatic reticulocytosis—often in the 20% range in IDA, less so in AAICI
• Blood loss can also be iatrogenic in combination with low-level hemolysis, DIC and reduced RBC life span in the ICU.