The survival of red cells in the circulation can
be measured in a variety of ways: (1) by labeling with isotopes,
particularly 51Cr, and assessing the disappearance of the
tag from the circulation over time; (2) by labeling the erythrocytes
with biotin or fluorescent dye and measuring this marker over time;
(3) by determining the disappearance of transfused allogeneic erythrocytes
using immunologic markers; and (4) by measuring the excretion of
carbon monoxide (CO), a product of heme catabolism.
Such studies show that normal human red cells have a
finite life span averaging 120 days, with very little random destruction.
During maturation of the reticulocyte, cell density increases, but
after a few days of intravascular life span there is little further
increase in density or other changes in the physical property of the
red cells. Thus cell density is not a good marker for aged red cells.
This has made the senescent changes in the red cell that mark it
for destruction difficult to study. Candidates for such changes
include changes in membrane band 3 and exposure of phosphatidylserine
on the membrane, which may be of major importance.
Acronyms and Abbreviations
Acronyms and abbreviations that appear in this chapter
include: ADP, adenosine diphosphate; AMP, adenosine monophosphate;
C3, third component of complement; 14C, radioactive
carbon; CO, carbon monoxide; 51Cr, chromium-51; 50Cr,
chromium-50; DFP, diisopropylfluorophosphate; 55Fe or 59Fe,
radioactive iron; G-6-PD, glucose-6-phosphate dehydrogenase; Ig, immunoglobulin; 111In, indium-111; 15N, nitrogen;
PK, pyruvate kinase; 99mTc, technetium-99m.
Measurement of Red Cell Destruction
The original method for the measurement of the red cell life
span consisted in the transfusion of cells that were compatible
but identifiable immunologically—the Ashby technique; type
O red cells were infused into individuals with type A or B cells
and the recipients’ own cells were removed using anti-A
or anti-B serum.1 During World War II and shortly
after, this method was used extensively, but in recent years, because
of the hazards associated with the administration of allogeneic
erythrocytes, it has been completely replaced by techniques based
on labeling of autologous blood.
In 1946, Shemin and Rittenberg demonstrated that the incorporation
of nitrogen (15N)-labeled glycine into heme could be used
to measure the life span of the red cells.2 Since
then a number of other isotopic methods have been developed. These
can be divided into three groups: (1) those that label a cohort
of cells, (2) those that label cells randomly, and (3) those that
use indirect measurements such as the rate of production of red
cells or the rate of heme breakdown. The first two classes yield
information about the nature of the shortening of the red cell life
span, age-dependent or random. The last group yields only mean life