Erythropoietin responses to progressive blood loss over 10 days in the ovine fetus

Long-term loss of fetal blood can occur with fetomaternal hemorrhage, vasop revia, or placental previa. Our objective was to determine the effects of p rogressive fetal blood loss over 10 days on fetal plasma erythropoietin (EP O) concentration and its relationship to arterial PO2, hematocrit, and the volume of blood loss. Late-gestation fetal sheep (n = 8) were hemorrhaged d aily at a rate of 1 ml/min over 10 days. The extent of hemorrhage differed in each fetus and ranged from 30 to 80 ml/day, with the cumulative volume r emoved ranging from 78 to 236 ml/kg estimated fetal weight. Four fetuses se rved as time controls. EPO concentration measurements were by radioimmunoas say. Statistical analyses included regression, correlation, and analysis of variance. We found that EPO and arterial PO2 were unchanged until the cumu lative hemorrhage volume exceeded 20-40 ml/kg. Once this threshold was exce eded, plasma EPO concentration increased progressively throughout the study and averaged 14.3 +/- 3.2 times basal values on day 10. EPO concentration, arterial PO2, and hematocrit changes were related curvilinearly to cumulat ive hemorrhage volume (P< 0.01), whereas the relationship between plasma EP O and arterial PO2 was log linear (P< 0.001). We conclude that 1) fetal pla sma EPO concentration and arterial PO2 are insensitive to a slow, mild-to-m oderate blood loss over several days; 2) unlike the rapid return of EPO to normal within 48 h after acute hemorrhage, fetal EPO concentration undergoe s a progressive increase with moderate-to-severe blood loss over several da ys; 3) the long-term hemorrhage-induced changes in EPO are best correlated with arterial PO2; and 4) the fetal EPO response to hemorrhage does not app ear to be limited by the fetus's ability to produce EPO.