Hemoglobin loss from erythrocytes in vivo results from spleen-facilitated vesiculation

Utrecht University, Utrecht, Utrecht, Netherlands
Blood (Impact Factor: 10.45). 02/2003; 101(2):747-51. DOI: 10.1182/blood-2002-02-0500
Source: PubMed


Previous studies have shown that approximately 20% of hemoglobin is lost from circulating red blood cells (RBCs), mainly during the second half of the cells' life span. Because hemoglobin-containing vesicles are known to circulate in plasma, these vesicles were isolated. Flow cytometry studies showed that most RBC-derived vesicles contain hemoglobin with all hemoglobin components present. The hemoglobin composition of the vesicles resembled that of old RBCs. RBC cohort studies using isotope-labeled glycine have been described, which showed a continuous presence of this label in hemoglobin degradation products. The label concentration of these products increased during the second half of the RBC life span, accompanied by a decrease within the RBC. It is concluded that the hemoglobin loss from circulating RBCs of all ages can be explained by shedding hemoglobin-containing vesicles. This loss occurs predominantly in older RBCs. Apparently the spleen facilitates this process since asplenia vesicle retention within RBCs of all ages has been described, accompanied by an increase in the percentage of total HbA(1). The present study shows that in old RBCs of asplenic individuals, the decrease of hemoglobin content per cell such as seen in old RBCs of control individuals is absent due to an increase in the absolute amount of HbA(1c) and HbA(1e2). It is concluded that hemoglobin-containing vesicles within old RBCs are "pitted" by the spleen.

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Available from: Giel J C G M Bosman,
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    • "In the mean-time all inclusion bodies are also being removed. In splenectomized patients or in patients with a non-functional spleen, phagocytosis of the inclusion bodies fails and results in a retention of a variety of intracellular inclusions within the RBC, such as Howell-jolly bodies (inclusions of nuclear chromatin remnants) (Wilkins and Wright, 2000), Heinz bodies (inclusions of denatured hemoglobin caused by oxidative damage) (Wilkins and Wright, 2000) siderocytes (RBC containing granules of iron that are not part of the cell's hemoglobin) (Wilkins and Wright, 2000) and Pappenheimer bodies inclusion bodies formed by phagosomes that have been engulfing excessive amounts of iron (Wilkins and Wright, 2000). Back in 1957 Crosby already showed that when siderocytes, tagged with radioactive chromium, were injected into a healthy patient with a functional spleen, there was a decline in siderocyte count without the loss of chromium labeled RBC. "
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    • "The striking resemblance between the hemoglobin composition of blood-borne vesicles and that of old erythrocytes, supports the conclusion that there is a continuous loss of hemoglobin in vesicles, which accelerates during the second half of the erythrocyte lifespan (Willekens et al., 2003). In the oldest erythrocytes of asplenic individuals , the decrease in hemoglobin is absent, concomitant with an increase in the absolute amounts of glycated and otherwise modified hemoglobin species (Willekens et al., 2003). Together with the previous observations that erythrocytes of patients without a functional spleen have an increased number of hemoglobincontaining vacuoles (Reinhart and Chien, 1988), and that there is a positive relation between the vacuole-containing erythrocytes and the percentage HbA1c (De Haan et al., 1988), these data suggest that hemoglobin-containing vesicles within old erythrocytes are removed from the erythrocytes in the spleen. "
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