The hematologic and plasma iron responses to severe fetal hemorrhage in the ovine fetus.
OBJECTIVE
We previously reported that the ovine fetus does not significantly increase its red blood cell production rate after a 40% loss of blood in spite of a transient elevation in plasma erythropoietin concentration. In this study we hypothesized that, in response to a more severe loss of blood, the ovine fetus would undergo a sustained rise in plasma erythropoietin concentration and an augmentation in its red blood cell mass expansion rate.


METHODS
Twelve chronically catheterized fetal sheep (six control and six hemorrhaged) were studied beginning at 126 +/- 1 (SE) days' gestation. Fetal blood volume, plasma volume, red blood cell mass, reticulocyte count, plasma erythropoietin level, and plasma iron level were measured for 10 consecutive days. On days 1, 2, and 3 the hemorrhaged fetuses had an average of 102 +/- 4 ml per day of blood removed at a rate of 1 ml/min for a total of 305 +/- 10 ml of blood removed. Statistical analysis was by one- and three-factor analysis of variance.


RESULTS
Control animals had a progressive increase in blood volume, plasma volume, and red blood cell mass throughout the 10-day protocol. Reticulocyte counts and plasma iron and erythropoietin levels did not change. In fetuses at 24 hours after the third hemorrhage blood volume averaged 9.3% below (p = 0.03) and plasma volume averaged 16.4% above (p = 0.04) that in the control animals. Thereafter blood and plasma volumes expanded at rates similar to controls. Erythropoietin increased (p < 0.001) but returned to prehemorrhage values by day 7. Posthemorrhage expansion of the red blood cell mass in the hemorrhaged animals was 1.9 times controls (6.8% +/- 0.9%/day vs 3.5% +/- 0.5%/day, p = 0.003). Fetal reticulocyte counts remained elevated throughout the posthemorrhage observation period (p < 0.001). The fetal plasma iron concentration decreased (p < 0.0001) and remained depressed. The recovery of red blood cell mass and the 10-day mean plasma iron concentration were highly correlated (p = 0.01, r = 0.91).


CONCLUSIONS
The ovine fetus significantly increases its release of red blood cells in response to a severe hemorrhage. Further, the ability of the fetus to restore its red blood cell mass appears to be dependent on the plasma iron concentration.
Shields
L E
LE
Department of Reproductive Medicine, University of California, San Diego, La Jolla 92093-0802, USA.
Widness
J A
JA
Brace
R A
RA
D000818:Animals; D001810:Blood Volume; D004921:Erythropoietin / Q000097:blood; D005260:Female; D005312:Fetal Blood / Q000378:metabolism*; D005333:Fetus / Q000502:physiology*; D005865:Gestational Age; D006400:Hematocrit; D006470:Hemorrhage / Q000097:blood / Q000196:embryology*; D007501:Iron / Q000097:blood*; D010953:Plasma Volume; D011247:Pregnancy; D017701:Reticulocyte Count; D012756:Sheep / Q000196:embryology*
D004921:Erythropoietin; D007501:Iron