The hematologic and plasma iron responses to severe fetal hemorrhage in the ovine fetus

Abstract

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.

Study design: 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).

Conclusion: 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.