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Prepublished online as a Blood First Edition Paper on August 1, 2002; DOI 10.1182/blood-2002-02-0500.
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Blood, 15 January 2003, Vol. 101, No. 2, pp. 747-751
RED CELLS
Hemoglobin loss from erythrocytes in vivo results from
spleen-facilitated vesiculation
Frans L. A. Willekens,
Bregt Roerdinkholder-Stoelwinder,
Yvonne A. M. Groenen-Döpp,
Harry J. Bos,
Giel J. C. G. M. Bosman,
Annegeet G. van den
Bos,
Arie J. Verkleij, and
Jan M. Werre
From the Department of Clinical Chemistry, Rijnstate
Hospital, Arnhem; Sanquin Blood Bank Zuid Oost Nederland; the
Department for Bloodtransfusion and Transplantation Immunology and the
Department of Biochemistry, University Medical Center, Nijmegen; and
the Department of Molecular Cellbiology, University of Utrecht, The
Netherlands.
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 HbA1.
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 HbA1c and HbA1e2. It is concluded that
hemoglobin-containing vesicles within old RBCs are "pitted" by the spleen.

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