Hepcidin and Anemia in Trauma

Anemia is common in trauma patients and is associated with a high rate of blood transfusion.
The pathophysiology of this anemia is "anemia of inflammation" and develops via 3
mechanisms: impaired iron regulation, shortened red blood cell life span, and reduced rate
of erythropoiesis. Once iron enters cells (enterocytes and macrophages), the iron export
protein ferroportin controls egress. Hepcidin, a peptide made in the liver, is the key
regulator of iron homeostasis. Hepcidin binds to ferroportin, leading to its ultimate
degradation. Hepcidin reduces iron availability via 2 mechanisms: decreased absorption of
iron across the GI tract and decreased release of iron from the reticuloendothelial system.
It therefore induces a functional iron deficiency by shuttling iron into the macrophages and
making it unavailable for erythropoiesis. Hepcidin is decreased by iron deficiency, most
anemias, and tissue hypoxia. Hepcidin is upregulated by iron excess and inflammation.
Hepcidin likely plays an important role in the acute inflammatory response that occurs with
trauma. However, no studies have measured hepcidin in critically ill trauma patients. If
serum hepcidin levels are elevated in trauma, this will confirm that inability to use
existing iron stores is part of, if not key to, the anemia of trauma and critical illness.
This has important implications since the use of blood transfusion for anemia treatment may
further induce an inflammatory response with resultant suppression of native erythropoiesis.

The investigators hypothesize that hepcidin will be increased and erythropoietin decreased
early after trauma and that resolution of anemia will not occur until late (28-31 days). By
measuring time-dependent changes in hemoglobin, hepcidin, cytokine, and erythropoietin
concentrations in trauma patients, the investigators can critically examine the
inter-relationships to target potential therapeutic strategies for the treatment and
amelioration of anemia in trauma and critical care.

Inclusion Criteria:

1. Trauma patient

2. Age 18 years or older

3. Admitted to ICU

4. Anemic (Hct < 34.5%)

Exclusion Criteria:

1. Pre-existing hematological disorder

2. Pre-existing diagnosis of anemia or other known iron disorder

3. Chronic renal failure

4. Use of recombinant erythropoietin

5. Treatment with systemic immunosuppressant or cytotoxic drugs

6. Pregnancy

7. Patients not expected to survive