Original article
Red blood cell survival and kinetics during pregnancy

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Abstract

Profound changes occur during pregnancy in the maternal hematopoietic system in order to meet the needs of the developing fetus and of the mother. By presenting the available data in one review, this review links all known hematopoietic events that occur during normal and certain abnormal pregnancies. Erythropoietin and erythrocyte production are increased during normal pregnancy while erythrocyte mass per unit of body weight remains constant throughout the entire pregnancy, and hemoglobin and hematocrit continuously decrease into the third trimester. Erythrocyte life span is decreased during normal pregnancy due to ‘emergency hemopoiesis’ in response to elevated erythropoietin levels. In preeclampsia, maternal erythrocytes are of similar to non-pregnant state age distribution, while fetal erythrocytes are of younger age distribution than in normal pregnancy. In gestational diabetes, maternal erythrocyte age distribution is similar to that of normal pregnancy. In multifetal pregnancy, maternal erythrocyte age distribution is younger than that of normal pregnancy.

Introduction

The erythrocyte is a unique cell that delivers oxygen and has a finite life span. During the process of its maturation in the bone marrow, the cell loses its nucleus, intracellular organelles, ribosomes, RNA and mitochondria [1]. The mature mammalian erythrocyte is a bidiscoidal cell composed of a cell membrane, hemoglobin and a variety of enzymes. During its life span in the circulation, various changes in structure, composition, biochemical, biophysical and immunological characteristics occur [1]. The erythrocyte becomes smaller in size and its specific gravity (i.e. density) increases [2], [3]. Studies of most enzymes (G6PD, catalase, glutathione reductase, glutathione peroxidase, aldolase A, pyruvate kinase, acethylcholine esterase and others), particularly those involved in protection against oxidative damage, have shown reduced activity as a function of age [4], [5]. Surface sialic acid is lost from the erythrocyte membrane with aging resulting in decreased electronic mobility and lower negative charge density of older erythrocytes [2], [6]. Alterations in the erythrocyte submembrane skeletal network with subsequent changes of surface charge topography accompany the normal process of aging in the erythrocyte [2].

The fact that pregnancy is associated with a specific hematologic changes was recognized as early as 1857 [7]. Profound changes occur during pregnancy in the maternal hematopoietic system in order to meet the needs of the developing fetus and of the mother [8]. The first recognized and probably most prominent hematologic change during pregnancy is hypervolemia [9], [10], [11]. The hypervolemia protects the mother from hypotension in the second half of pregnancy when sequestration of blood in low extremities occurs upon standing, sitting or lying supine and from hemorrhage at the time of delivery [8]. It also prevents hypovolemia after high peripheral blood loses. Moreover, the hypervolemia is needed to satisfy the increased circulatory requirement in order to sustain the fetal-placental unit [12].

The purpose of this review is to summarize the recent data on the red blood cell alterations and kinetics during pregnancy.

Section snippets

Normal pregnancy

The circulating blood is composed of cells of all ages. Reticulocytes just released from bone marrow, ‘young’ cells that matured recently and ‘old’ cells, that will be removed from the circulation in the next few hours or days are present. Therefore, the analysis of the red cell population cannot be looked at as an absolutely homogeneous entity but rather in terms of population dynamics and statistics [13]. Determination of age distribution of the red cell population reflects the process

Puerperium

An increased erythropoietic activity is present in the early puerperium [46]. During immediate and early puerperium the hemoglobin and hemotocrit remain fairly stable in spite of an acute reduction in the blood volume that occurs during delivery [46]. This is in contrast to the situation in non-pregnant individuals who usually respond with a volume expansion and a subsequent marked decrease in hematocrit. There is no evidence of sequestration of erythrocytes during parturition [47].

We speculate

Preeclampsia

Erythrocyte composition is altered in preeclampsia [52]. The levels of intracellular calcium [52], potasium chloride and total osmoles were greater in preeclampsia compared to normal pregnancy [53]. These changes could be detected as early as 14 weeks gestation [53]. The changes are probably compensatory reflecting the plasma osmolality homeostasis [53]. The total blood volume is reduced in preeclampsia [54], while colloid osmotic pressure is lower [55].

Erythrocyte morphology is altered in

Gestational diabetes

Erythrocytes aggregation increases progressively throughout pregnancy in diabetic patients compared to non-diabetics [63], [64]. Otherwise, blood rheology is unalterred in diabetic pregnant women as compared to non-diabetic pregnant women [64]. The average MCV of erythrocytes in pregnant diabetic women [Class A2 (insulin requiring) gestational diabetes] is similar to that in pregnant non-diabetic women [65]. Women with pregnancy complicated by Class A2 gestational diabetes have a higher

Multiple pregnancy

A higher reticulocytes count [67] and average MCV of erythrocytes [67], [68] were noticed in twin as compared to normal singleton pregnancies. The hemoglobin levels in twin pregnancy are lower than the levels in singleton pregnancy in the first and the second trimesters of pregnancy and similar in the third trimester [69]. The lower hemoglobin levels are associated with multiparity [69].

The erythrocyte population of women with twin gestation shortly before delivery has a larger proportion of

Fetal red blood cell

Fetal erythrocytes during normal pregnancy are of higher MCV as compared to adult erythrocytes [71]. The cumulative DDC curve of fetal erythrocytes during normal pregnancy represents erythrocytes of a lower specific density as compared to erythrocytes of pregnant women (Fig. 4) [59], [71]. This shift in age population of erythrocytes reflects a shorter life span of fetal erythrocytes in comparison to maternal erythrocytes because a shift to the right in the DDC curve is associated with a

Conclusion

In general, the pattern of erythrocytes’ aging during pregnancy follows a lucid model as illustrated by the curves in Fig. 4. It relies on two interdependent factors: the life span of erythrocytes and the erythropoietin level. As erythrocyte life span becomes shorter and/or erythropoietin level becomes higher, the age distribution of erythrocytes shifts further towards a younger population.

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