EPO has a long history: EPO-2 EPO-3 may reduce mortality in trauma but concerns about thromboembolic events and efficacy have limited application.

EPO is a pleiotropic cytokine and receptors exist in the blood-brain barrier. In response to hypoxia EPO is produced within the brain. Hence worthy of investigation:

Double-blind, placebo-controlled multi-centre trial

  • GCS < 13
  • Non-penetrating TBI
  • Hb < = normal
  • < 24 h since traumatic injury
  • Valid consent


  • EPO 40 000 IU or placebo SC
    • First dose was administered within 24 h of the estimated time of traumatic brain injury
    • Then weekly for a maximum of three dose
  • Baseline screening USS < = 7 of lower limbs for DVT

Main outcome GOS-E at 6 months

  • GOS-E of 1–4 (death, vegetative state, and severe disability)
  • GOS-E of 5–8 (moderate disability and good recovery)

606 randomised after inclusion / exclusion

Populations well matched

  • Mean age 35
  • Majority male
  • Mainly RTC
  • Most had severe TBI (GCS 3-8)

No effect on proportion with severe disability at 6/12

No increase in thrombotic events (including VTE and MI)

May reduce mortality – 5% ARR at 6/12 but does not achieve statistical significance


Becomes significant after sensitivity testing but this is exploratory

Rates of proximal DVT in TBI 17%

Conclusion: Following moderate or severe traumatic brain injury, erythropoietin did not reduce the number of patients with severe neurological dysfunction (GOS-E level 1–4) or increase the incidence of deep venous thrombosis of the lower limbs. The effect of erythropoietin on mortality remains uncertain.

Erythropoietin in traumatic brain injury (EPO-TBI): a double-blind randomised controlled trial