epoetin-alfa and Acute-Disease

Erythropoietin and its receptor function as primary mediators of the normal physiological response to hypoxia. Erythropoietin is recognized for its central role in erythropoiesis, but studies in which recombinant human erythropoietin (epoetin alfa) is injected directly into ischaemic rodent brain show that erythropoietin also mediates neuroprotection. Abundant expression of the erythropoietin receptor has been observed at brain capillaries, which could provide a route for circulating erythropoietin to enter the brain. In confirmation of this hypothesis, systemic administration of epoetin alfa before or up to 6 h after focal brain ischaemia reduced injury by 50-75%. Epoetin alfa also limited the extent of concussive brain injury, the immune damage in experimental autoimmune encephalomyelitis and excitotoxicity induced by kainate. Thus, systemically administered epoetin alfa in animal models has neuroprotective effects, demonstrating its potential use after brain injury, trauma and multiple sclerosis. It is evident that erythropoietin has biological activities in addition to increasing red cell mass. Given the excellent safety profile of epoetin alfa, clinical trials evaluating systemically administered epoetin alfa as a general neuroprotective treatment are warranted.

Topics: Acute Disease; Animals; Autoimmune Diseases; Brain; Brain Ischemia; Cerebral Cortex; Encephalitis; Epoetin Alfa; Erythropoietin; Humans; Kainic Acid; Neuroprotective Agents; Recombinant Proteins; Stroke; Wounds, Nonpenetrating

This study was performed to evaluate whether increasing hemoglobin before ascent by prophylactic erythropoietin injections prevents acute mountain sickness (AMS). This open-label, randomized, controlled trial involved 39 healthy volunteers with hemoglobin ≤ 15.5 g/dL who were divided randomly into erythropoietin (n=20) and control (n=19) groups. Epoetin alpha 10,000 IU injections were given weekly for four consecutive weeks. On day 1, and 7 days after the last injection (day 29), oxygen saturation (SaO2), and hemoglobin were measured. The subjects departed Seoul on day 30 and arrived at Annapurna base camp (ABC, 4,130 m) on day 34. AMS was diagnosed when headache and Lake Louise score (LLS) of ≥ 3 were present. Immediate descent criteria followed US Army recommendations. Two groups differ in hemoglobin levels on day 29 (15.4 ± 1.1 vs 14.2 ± 1.0 g/dL, P=0.001). At ABC, erythropoietin group had a significantly lower mean LLS, AMS incidence, and number of subjects who met immediate descent criteria. Multiple logistic regression analysis showed that SaO2<87% and control group, but not hemoglobin<15.0 g/dL, independently predicted satisfaction of immediate descent criteria. Erythropoietin-related adverse effects were not observed. In conclusion, erythropoietin may be an effective prophylaxis for AMS.(Clinical Trial Registry Number; NCT 01665781).

Topics: Acute Disease; Adult; Altitude Sickness; Blood Pressure; Drug Administration Schedule; Epoetin Alfa; Erythropoietin; Female; Headache; Hemoglobins; Humans; Incidence; Logistic Models; Male; Middle Aged; Odds Ratio; Oxygen; Recombinant Proteins; Surveys and Questionnaires

Recent studies in animal models indicate that recombinant human erythropoietin (rhEPO) is very effective in enhancing neurological recovery after spinal cord injury (SCI). We aimed to evaluate the effect of rhEPO plus methylprednisolone sodium succinate (MPSS) compared to MPSS alone to improve neurological function of patients after SCI in a randomized clinical trial. During a 15-month period 30 patients presenting to emergency departments of two university affiliated hospitals within less than 6 hours after acute SCI were randomized to two groups. Both groups received MPSS 30 mg/kg initially and 5.4 mg/kg every hour till 23 hours if admitted within 3 hours and till 47 hours if recruited within 3-6 hours after injury. Group EPO also received 500 unit/kg rhEPO on admission and another 500 unit/kg 24 hours later instead of placebo in group MPSS. Neurologic evaluation was performed on admission, 24, 48, 72 hours and one and 6 months later. Range of patients' age was 18-65 years. There was no significant difference between patients receiving two types of treatment in neurological exam on admission (P=0.125), 24 hours after admission (P=0.108) and 48 hours after admission (P=0.085). However, one week (P=0.046), one month (P=0.021) and six months (P=0.018) after admission these differences were significant. MPSS plus rhEPO started within 6 hours after acute spinal injury may be more effective than MPSS plus placebo in improvement of neurologic dysfunction. More studies with larger sample sizes are warranted.

Topics: Acute Disease; Adolescent; Adult; Aged; Epoetin Alfa; Erythropoietin; Female; Hematinics; Humans; Male; Methylprednisolone; Middle Aged; Neuroprotective Agents; Recombinant Proteins; Spinal Cord Injuries; Treatment Outcome