Titers of ABO antibodies

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250 Rev Bras Hematol Hemoter. 2011;33(4):250-8
Scientific Comments
Titers of ABO antibodies in group O blood donors: patient safety and blood
product supply remain a challenge
Conflict-of-interest disclosure:
The authors declare no competing
financial interest
Submitted: 7/28/2011
Accepted: 7/29/2011
Corresponding author:
Gregory Denomme
Immunohematology Reference Laboratory,
Blood Center of Wisconsin,
638 18th Street, Milwaukee,
WI 53201-2178, United States
gregory.denomme@bcw.edu
www.rbhh.org or www.scielo.br/rbhh
DOI: 10.5581/1516-8484.20110067
Immunohematology Reference
Laboratory, Blood Center of
Wisconsin, Milwaukee, WI,
United States
Gregory Denomme Overt hemolysis from the transfusion of ABO incompatible plasma containing high
titer anti-A or anti-B is a rare event. Plasma from group O donors and the transfusion of
single donor platelets are most often associated with these reactions when transfused to
group A or AB recipients. Several studies over the years have evaluated donor ABO
antibody class, titer, and subclass in an effort to understand the breadth of the problem and
reduce or eliminate this potentially serious immune complication of transfusion. In this
regard, de França et al.(1) in this issue of the Revista Brasileira de Hematologia e
Hemoterapia underscore the lack of a national standard of practice to guide the transfusion
of incompatible ABO plasma transfusions. They point out that seminal work, started more
than 2 decades ago, has yet to set policy and safety guidelines with the use of plasma that
potentially contain life-threatening levels of anti-A or anti-B.(2) de França et al. examined
over 5% of their blood donors included males and females across all age groups in an effort
to understand which donors pose the biggest risk for the transfusion of high-titer anti-A or
anti-B. Not surprising they found that ABO antibody titers decrease with age, with older
males having the lowest titers by age 50. Cumulatively, nearly 1 in 10 plasma contain anti-
A titers ≥ 128. Their work suggests that targeting ABO incompatible plasma and platelets
from older males would lower the risk, if one assumes titers over 64 by the doubling-
dilution method (generally titers > 100 are regarded as critical) pose significant risk of
hemolysis. However, there is still a 1:20 (5.3%) chance that plasma from males over 50 will
contain a titer ≥ 128. Thus, targeting sex and specific age groups as surrogate markers for
the transfusion of ABO incompatible platelets could hardly be considered safe practice,
although it would be a step in the right direction.
The lack of a standardized test and the impact on blood product availability is
having an effect on the ability to drive policy and develop meaningful guidelines.
Methodology appears to be a major issue. de França et al. used direct agglutination,
however, other studies have used a test tube indirect antiglobulin test (IAT), gel micro-
column agglutination in an IAT, and flow cytometry to measure the amount of anti-A,B,
anti-A and anti-B. The measurement of anti-A,B does not appear to provide any additional
information on titers when compared to anti-A (de França et al.(1) Table 1). One problem
with defining a standard may be the lack of studies necessary to correlation these methods
and thus an agreement on the critical titer for which non-ABO matched platelet
transfusions should be avoided. European blood centers have addressed the issue of
titers and have identified low-risk titers for ABO incompatible plasma transfusions. It is
important to establish critical ABO antibody titers by population (national), using the
most clinically relevant method, since it appears that diet and ethnicity may result in
significant differences in titers.(3,4) Performing population estimates for anti-A and anti-B
levels across blood donors determines the frequency of high titers and help estimate the
cost of implementing a nationalized testing policy. de França et al. have made a significant
contribution in this regard. However, the challenge remains to quantify the impact that
such a policy will have on the provision of plasma containing platelet products to
recipients.(5)
References
1. de França ND, Poli MC, Ramos PG, Borsoi CS, Colella R. Titers of ABO antibodies in group O blood
donors. Rev Bras Hematol Hemoter. 2011;33(4):259-62.
2. Rieben R, Buchs JP, Flückiger E, Nydegger UE. Antibodies to histo-blood group substances A
and B: agglutination titers, Ig class, and IgG subclasses in healthy persons of different age
categories. Transfusion. 1991;31(7):607-15.Comment in: Transfusion.1991;31(7): 577-
80 .
3. Mazda T, Yabe R, NaThalang O, Thammavong T, Tadokoro K. Differences in ABO antibody levels
among blood donors: a comparison between past and present Japanese, Laotian, and Thai
populations. Immunohematology. 2007;23(1):38-41. Erratum in: Immunohematology. 2008;24
(1):28.
Rev Bras Hematol Hemoter. 2011;33(4):250-8 251
4. Daniel-Johnson J, Leitman S, Klein H, Alter H, Lee-Stroka A,
Scheinberg P, et al. Probiotic-associated high-titer anti-B in a
group A platelet donor as a cause of severe hemolytic transfusion
reactions. Transfusion. 2009;49(9):1845-9.
5. Josephson CD, Castillejo MI, Grima K, Hillyer CD. ABO-mismatched
platelet transfusions: strategies to mitigate patient exposure to
naturally occurring hemolytic antibodies. Transfus Apher Sci.
2010;42(1):83-8. Review.
xxx
Scientific Comments
Confidential donation confirmation as a alternative exclusion
Conflict-of-interest disclosure:
The authors declare no competing
financial interest
Submitted: 7/12/2011
Accepted: 7/13/2011
Corresponding author:
Thelma T Gonçalez
Blood Systems Research Institute
270, Masonic Avenue
94118 San Francisco, CA, USA
ttgon@uol.com.br
www.rbhh.org or www.scielo.br/rbhh
DOI: 10.5581/1516-8484.20110068
Blood Systems Research Institute,
San Francisco, CA, United States
Thelma T Gonçalez In this issue of the Revista Brasileira de Hematologia e Hemoterapia, Loureiro et al.
present their evaluation of the use of confidential donation confirmation (CDC), i.e., release
of blood units from donors who have confirmed that their blood may be used for transfusion
by choosing the "yes" option.(1)
The conclusion of this case-control study is that CDC did not reduce the residual risk
of transfusion-transmitted infections (TTIs) nor did it deter at-risk donors from donation.
In brief, no real benefit was associated with the use of CDC.
The safety of the blood supply has been improved over the years by the progressive
implementation of measures aimed at reducing the risk of TTIs. The use of voluntary non-
remunerated donors, the implementation of donor education programs, the careful selection
of donors interviewed before their donation using donor questionnaires and the
development of sensitive laboratory screening assays have all contributed tremendously
to the improvement in blood safety. Over the last decade, the use of nucleic acid amplification
technology (NAT) has improved blood safety by reducing the window period and the
residual risk of human immunodeficiency virus (HIV) transmission around the world.(2,3)
Nowadays, a lower prevalence of infectious diseases is observed among blood donors and
the immunological window periods for these infections have been shortened remarkably.(3)
However, global and regional differences persist due to higher or lower incidences of
diseases and, because of the window period, there will always be a residual risk for TTIs.
The improvement in blood safety therefore requires ongoing effort within a wide rangeof
contexts.
In 1986, the U.S. FDA recommended the use of confidential unit exclusion (CUE).(4)
This approach allows at-risk donors to confidentially exclude their blood from being used
for transfusion. However, the use of CUE is controversial as many authors have reported
that CUE has low sensitivity, a low positive predictive value(5-7) and no proven benefit in
terms of improving blood safety. Furthermore, CUE has even been associated with a small
but constant loss of apparently safe donations.(7) For this reason, the CUE is no longer in
use in most U.S. blood banks(8) However, CUE is still used or recommended in other countries,
such as in the United Kingdom,(9) Switzerland,(9) Iran,(10) Brazil(11,12) and Germany.(9)
The use of CUE has been evaluated in countries where NAT screening is performed
and where the residual risk of HIV transfusion-transmission is lower, such as in Germany
and Canada and results have shown that the sensitivity and positive predictive values of
CUE are very low and it has minimal impact on transfusion safety.(9,13) Also, the researchers
concluded that the efficacy and usage rate of CUE depend very much on the demographic
characteristics of donors as well as the design of the CUE form and procedures.
In Brazil, NAT screening for HIV is not performed routinely by most blood banks.
This results in a longer infectious window period and substantially greater residual risk of
transfusion-associated transmission of HIV than in the U.S.(2,3) and Europe.(14,15) In Brazil,
estimates of HIV incidence are approximately 10-fold higher in first-time donors than in the
U.S.(3) and Europe.(15) A recent study by Dr. Sabino et al.(16) showed that even with the
implementation of NAT, the risk of residual HIV in Brazil will remain higher than it was in the
U.S. prior to NAT screening.(3,17) In this case, the use of CUE could potentially help exclusion
of units donated during the HIV window period.(18)
The CUE or CDC approaches have been used in several Brazilian blood banks in
compliance with local regulations or recommendation.(12) Mendrone et al.(19) found that, in