TRANSFUSION
REACTIONS
DUE TO
LEUKOCYTE
AGGLUTININS
Robert D. Gens, M.D.
Department of Pediatrics, University of Pennsylvania, and the Children’s Hospital of Philadelphia
PRESENT ADDRESS: (Office) Mid-Hudson Medical Group, Fishkill, New York.
370
PEDIATRICS, March 1961
p
ECENT advances in immunohematology have included the recognition thathuman leukocytes contain antigens that can
induce the formation of isoantibodies’’ in recipients of blood transfusions and
proba-bly also in nontransfused mothers in
associ-ation with multiple pregnancies. While
there is no doubt8 that some of the
leuko-cyte antigens are the same as those of the
erythrocytes, it appears that leukocytes pos-sess antigens that erythrocytes lack.’’#{176}
It is not surprising, therefore, that Brit-tingham4 and Killmann’ have noted that chills and fever may occur during
transfu-sions of erythrocyte-compatible whole blood to patients whose serum contains leukocyte agglutinins, and that cilills and fever do not occur when the same patients received
leukocyte-poor blood.
During a study of leukocyte agglutinins in patients with various hematologic
dis-orders it was noted that several children who had received many blood transfusions had leukocyte agglutinins. Detailed studies
on one of these patients is the subject of this report.
PATIENT MATERIAL
The patient was a 14-year-old white male, of
Italian descent, with thalassemia major. He received his first blood transfusion when 11 months old, underwent a splenectomv 3 weeks later, and received 108 blood transfusions
during subsequent years. At 14 months of age a fever was noted during his fourteenth trans-fusion.
Since 5 years of age, chills, fever and leth-argy accompanied at least one-half of the trans-fusions, and nausea, vomiting and headache oc-casionally were noted. During many of the transfusions, regrettably, the recording of temperature and symptoms was inadequate for
retrospective evaluation. Had adequate records
been available it is possible that the recorded incidence of transfusion reactions would have
been higher. The febrile rise during transfusion typicalls.’ begins about 1 hour after the trans-fusion is started, reaches from 101.4 to 104.2#{176}F (38.6 to 40.1#{176}C), and lasts about 3 hours.
The blood given to this patient has always been compatible by the indirect Coombs cross-matching technique, has usually been onl’ 1 to 2 days old, and has been collected in acid-citrate-dextrose solution in glass bottles.
METHODS
Studies for Leukocyte Agglutinins
The technique of Dausset’#{176} was used to de-tect the presence of leukocyte agglutinins. This technique involves the mixing of a leu-kocvte suspension collected from normal donors with the serum of the patient under ex-amination. After incubation the mixture is
examined microscopically for evidence of
ag-glutination. Two controls, one using leukocyte suspensions without the patient’s serum and the other using erythrocyte suspensions (pre-pared from the specimen used for the leuko-cyte suspension) with the patient’s serum, were always employed. The leukocyte suspensions were prepared in silicone-treated equipment.
Transfusion Experiments
To examine the possibility that leukocyte agglutinins were responsible for this patient’s transfusion reactions, leukocyte-rich and leu-kocyte-poor fractions of blood were prepared according to the technique of Brittingham.4 These fractions were infused as follows: The
leukocvte-rich fraction of blood was infused until symptoms of a transfusion reaction ap-peared. A slow infusion of dextrose in water was then substituted and continued until the transfusion reaction appeared to abate. At this point the leukocvte-poor fraction of blood was substituted for the dextrose and water
in-fusion.
LI-LI’
4
LI’
I-SO 20 ISO 240 300 340
TIME (MINUTES)
INFUSIONS [R’cO. %GuCoSE siooo,AcT,u
FIG. 1.
ARTICLES 371
the recording of the subjective ol)servations was done by the author.
An alternate method of preparing
leukocyte-1oor blood has been devised in this hospital alld was used to prepare blood for this patient for subsequent transfusions. With this method 440 ml of whole blood, less than 6 days
old, is collected ill a glass bottle with 1 10 ml
ACD solution (NIH solution B). This blood,
after i)eing mixed by inversion, is centrifuged
at al)ont 1,000 rev/mm at 4 to 6#{176}Cin an JIlter-national PR-2 centrifuge for 20 minutes. A
1)l1snla aspirating needle#{176} is then inserted into the bottle and the tip of the needle directed
to the bottom of the bottle; 200 ml is then withdrawn into IlIl empty plasma container*
mcl used for a leukocyte-poor transfusion.
RESULTS
This patient’s serum agglutinated the leu-kocytes of 16 of 16 normal donors. No
autoagglu tmation of the patient’s
leuko-cytes was noted nor did the patient’s serum agglutinate the leukocytes of his motiler or
his father. The patient’s serum agglutinated
the leukocytes of the five donors used in the
transfusion portion of this study.
Figure 1 illustrates tile patient’s reaction
to a transfusion study. Approximately 1
hour after the start of a transfusion of
len-kocyte-rich blood (20,250/mm’) the patient
experienced a severe shaking chill. The transfusion was then stopped (205 ml had been given) and a slow infusion of 5 dex-trose in water substituted. Within 35
min-utes the patient developed fever and cx-ilibited lethargy. At this time he stated
that these symptoms were the same as those which ile had usually experienced during
previous transfusions. After tile patient’s temperature had ceased to rise and he said that he “felt better,” a leukocyte-poor
trans-fusion was substituted for the dextrose and water infusion. The patient’s temperature
then returned to a normal range and his
sation of this transfusion experiment still cx-hibited leukocyte agglutination activity.
Four subsequent transfusions of
leuko-cyte-poor blood, prepared by the alternate
method described above, have been given without inducing chills, fever or lethargy.
About
200 ml of leukocyte-poor blood wasused for each of these transfusions; the leukocyte content of the blood given ranged from 700/mm to 2,100/mm’ and the
hema-tocrit
from
58% to 61%.
DISCUSSION
Tile reactions to transfusions of routine
blood bank blood in patients who have de-veloped leukocyte agglutinins are
surpris-ingly
uniform.”
A
shaking
chill
begins
about 1 hour after the infusion is started, followed quickly by an elevation in body
temperature.
The
duration
of the
tempera-ture
elevation
depends
upon
the
length
of
transfusion, but usually the temperature has returned to normal within 3 hours after ces-sation of transfusion. Occasionally a slight
decrease in blood pressure has been re-ported. Chest pain, nausea, vomiting and
headache have been noted.
ag-372 TRANSFUSION REACTIONS
thalassemia major are receiving blood transfusions regularly. Only two of these
children have been found to have de-veloped leukocyte agglutinins.
The
elucidation
of
leukocyte
antigens
will probably clarify wily leukocyte
agglu-tinins develop infrequently in patients wll()
have received multipe blood transfusions
and, further, why patients who ilave
die-veloped leukocyte agglutinins are asymp-tornatic during the course of some blood
transfusions.
Because technical considerations make the
employment of a “leukocyte cross-match test” unsatisfactory for routine blood bank use, the preparation of letikocyte-poor blood by the alternate method just describedi seems to be an adequate technique to pro-vide blood for patients who exhibit a leu-kocyte agglutinin.
CONCLUSION
A patient who had received multiple
blood transfusions and whose serum ex-hibited a leukocyte agglutinin is reported.
This patient developed transfusion reac-tions characterized by chills, fever and
lethargy
when administered routineblood-bank and leukocyte-rich blood. No
trans-fusion
reaction
wasnoted
when
the
patient
received leukocyte-poor blood.
Acknowledgment
The author acknowledges with gratitude
the assistance of Dr. Irving
J.
Wolman inmak-ing available patients for this study and in making suggestions for the preparation of the
manuscript.
The General Analine and Film Company, New York, (lonated the polyvin’slpyrrolidone used for the preparation of the leukocvte sus-pensions.
REFERENCES
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leukocyte incompatibility.
J.
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hu-man sera. Arch. Intern. Med., 99:587,
1957.
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14:302, 1955.
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