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H e m a t o lo g y E d u c a t io n - European Hematology Association

H e m a t o lo g y E d u c a t io n - European Hematology Association

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S.R. S<strong>lo</strong>an<br />

Harvard Medical School<br />

& Children’s Hospital, Boston,<br />

Mass., USA<br />

Hemato<strong>lo</strong>gy Educat<strong>io</strong>n:<br />

the educat<strong>io</strong>n program for the<br />

annual congress of the <strong>European</strong><br />

Hemato<strong>lo</strong>gy Associat<strong>io</strong>n<br />

2011;5:381-384<br />

Transfus<strong>io</strong>n<br />

Immuno<strong>lo</strong>gic responders to red b<strong>lo</strong>od cell transfus<strong>io</strong>ns<br />

Risks associated with anti-RBC<br />

antibodies<br />

Al<strong>lo</strong>geneic red b<strong>lo</strong>od cell (RBC) transfus<strong>io</strong>ns<br />

expose patients to dozens to hundreds of foreign<br />

antigens that are exposed on erythrocyte<br />

membranes. Remarkably, RBC transfus<strong>io</strong>ns<br />

do not usually result in a detectable immune<br />

response and transfused RBCs usually have a<br />

normal lifespan. Occas<strong>io</strong>nally, however, an<br />

antibody response to one or more antigens<br />

occurs. Such an immune response can be dangerous<br />

for the patient, risking delayed<br />

hemolytic transfus<strong>io</strong>n react<strong>io</strong>ns, and/or<br />

hemolytic disease of the fetus and newborn.<br />

The severity of a delayed hemolytic transfus<strong>io</strong>n<br />

react<strong>io</strong>n depends in large part on<br />

whether the react<strong>io</strong>n is a primary immune<br />

response or whether it is a secondary<br />

immune response. If the response is a primary<br />

immune response, then the patient can<br />

deve<strong>lo</strong>p a relatively mild delayed hemolytic<br />

transfus<strong>io</strong>n react<strong>io</strong>n. However, secondary<br />

amanestic responses can be relatively rapid,<br />

and strong responses can cause severe<br />

delayed hemolytic transfus<strong>io</strong>n react<strong>io</strong>ns that<br />

in rare cases, can be fatal.<br />

Approaches to prevent risks associated<br />

anti-RBC antibodies<br />

B<strong>lo</strong>od banks have procedures to avoid<br />

severe delayed hemolytic transfus<strong>io</strong>n react<strong>io</strong>ns<br />

associated with secondary immune<br />

responses. These procedures are generally<br />

aimed at detecting and identifying RBC<br />

al<strong>lo</strong>antibodies pr<strong>io</strong>r to RBC transfus<strong>io</strong>ns and<br />

avoiding transfusing RBC units expressing<br />

the corresponding antigens.<br />

Although current b<strong>lo</strong>od bank approaches<br />

prevent the most potential ser<strong>io</strong>us delayed<br />

A B S T R A C T<br />

Al<strong>lo</strong>immunizat<strong>io</strong>n to RBC antigens is a significant risk factor for future transfus<strong>io</strong>ns and pregnancies.<br />

Analysis of patient databases strongly suggests that there is a distinct group of potential<br />

immuno<strong>lo</strong>gic responders to RBC transfus<strong>io</strong>ns. This group, comprising 13–20% of the general patient<br />

populat<strong>io</strong>n, is most likely genetically determined and is not related to disease. However, even potential<br />

immuno<strong>lo</strong>gic responders do not respond to most transfus<strong>io</strong>ns. Though it is unclear what factors determine<br />

which RBC transfus<strong>io</strong>ns will induce an immune response, animal models suggest that inflammatory<br />

signals may contribute to responsiveness to individual transfus<strong>io</strong>ns. When a patient responds to<br />

one antibody, he or she is more likely to make addit<strong>io</strong>nal antibodies, but deve<strong>lo</strong>pment of those addit<strong>io</strong>nal<br />

antibodies is a stochastic process. Youngest patients have the broadest repertoire of antibody<br />

responses. The anti-RBC antibody repertoire gradually declines with age.<br />

hemolytic transfus<strong>io</strong>n react<strong>io</strong>ns, they do not<br />

prevent all such react<strong>io</strong>ns. One deficiency in<br />

the current system concerns the fact that<br />

antibody screens are usually only performed<br />

pr<strong>io</strong>r to the anticipated transfus<strong>io</strong>ns, not in<br />

the weeks fol<strong>lo</strong>wing RBC transfus<strong>io</strong>ns. Tests<br />

performed several weeks after a transfus<strong>io</strong>n<br />

would be the most sensitive in detecting<br />

transfus<strong>io</strong>n induced antibodies. 1 Instead,<br />

however, standard practice usually involves<br />

waiting until a transfus<strong>io</strong>n itns anticipated to<br />

perform an antibody screen. Unfortunately,<br />

this may not detect pr<strong>io</strong>r immune responses<br />

because anti-RBC antibody titers often wane<br />

over time, often to undetectable levels after<br />

several years. 2 Although antibodies can<br />

wane over time, memory lymphocytes can<br />

persist throughout an individual’s life. These<br />

memory lymphocytes can mount a rapid,<br />

vigorous response, resulting in a severe<br />

delayed hemolytic transfus<strong>io</strong>n react<strong>io</strong>n even<br />

when no detectable antibody was present<br />

pr<strong>io</strong>r to a transfus<strong>io</strong>n.<br />

In addit<strong>io</strong>n to failing to prevent severe<br />

delayed hemolytic transfus<strong>io</strong>n react<strong>io</strong>ns,<br />

protocols primarily aimed at avoiding secondary<br />

immune responses to transfused erythrocytes<br />

ignore the risks posed by some<br />

antibodies to women and girls with child<br />

bearing potential. Some IgG antibodies can<br />

be transported across the placenta and react<br />

with fetal erythrocytes, resulting in hemolysis.<br />

The resulting clinical syndrome,<br />

hemolytic disease of the fetus and newborn,<br />

can be severe but rarely occurs during the<br />

first pregnancy of a non-transfused woman.<br />

Recognizing the risks posed by primary<br />

immune responses to erythrocyte antigens,<br />

most modern transfus<strong>io</strong>n services have<br />

adopted protocols to reduce the incidence of<br />

primary immune responses. Most transfus<strong>io</strong>n<br />

services have minimized transfus<strong>io</strong>n of<br />

Hemato<strong>lo</strong>gy Educat<strong>io</strong>n: the educat<strong>io</strong>n programme for the annual congress of the <strong>European</strong> Hemato<strong>lo</strong>gy Associat<strong>io</strong>n | 2011; 5(1) | 381 |

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