Experimental Induction of Caprylatedependent Albumin Antibodies ALI A. HOSSAINI, P H . D . , ALBERT J. WASSERMAN, M.D.,
AND GEORGE P. VENNART, M.D.
From the Department of Pathology and Department of Pharmacology, Medical College of Virginia, Virginia Commonwealth University, Richmond, Virginia
ABSTRACT
IN 1956, Weiner and associates4 reported the finding of three sera each of which strongly agglutinated all human cells ineluding their own only when the cells were suspended in an albumin medium, Over the years that followed, many examples of this serologic idiosyncrasy were re-
ported. Attempts were made to determine the nature of these agglutinins and the mechanism by which they agglutinated erythrocytes. Studies by Lovett and colleagues 3 and by Golde and co-workers' suggested that the phenomenon was immune in nature. T h e studies of Lovett and Moore 3 led to the postulate that the agglutinating factor was an antibody
; Received March 31, 1975; received revised manu-
••
•
•
,
•
c
script June 30, 1975; accepted for publication June 30, 1975.
directed against a minor determinant of some bovine serum albumins that formed
Presentedatthe27thAnnualMeeting0ftheAmencan Association or Blood Banks, November 9 - 1 4 ,
s o
1974, Anaheim, California.
Address reprint requests to Dr. Hossaini: Director of the School of Blood Banking, Medical College of Virginia, 1200 East Broad Street, Richmond, Virginia
23298.
,uble
ant
j g e r ) - a n t i b o d y complexes. Be° / r
cause of steric configuration, these cornp l e x e s n o n s p e c i f i c a l l y a d s o r b o n t o t h e SU1, . , , r of erythrocytes, causing them to dump1
r f a c e
in vitro. Golde, McGinnis and Holland
513
Downloaded from http://ajcp.oxfordjournals.org/ by guest on June 7, 2016
Hossaini, Ali A., Wasserman, Albert J., and Vennart, George P.: Experimental induction of caprylate-dependent albumin antibodies. Am J Clin Pathol 65: 513-517, 1976. A normal donor with the caprylate-dependent albumin agglutinins volunteered to receive 50 ml. of 25% caprylate-stabilized human albumin to determine the clinical significance of the antibodies. The donor manifested no clinical sign of a reaction. Samples of blood and urine collected before, during and after administration of albumin were subjected to extensive laboratory investigation. Biochemical, immunologic, hematologic, hemostatic and immunohematologic variables investigated showed only insignificant variations in all blood and urine samples. Results indicated that the infusion of albumin was safe, for the donor showed no sign of a hemolytic, febrile, allergic or anaphylactic transfusion reaction. However, since this is the first and only reported experiment of its kind, it is deemed advisable to exercise caution when administering albumin to patients who have caprylate-dependent albumin agglutinins until sufficient supportive data attesting to the complete safety of this procedure have accumulated. (Key words: Transfusion; Albumin; Antibodies; Transfusion reaction; Sodium caprylate; Caprylatestabilized albumin; Caprylate-dependent albumin agglutinins; Albumin autoagglutinins.)
514
HOSSAINI, WASSERMAN, AND VENNART
T h e suggestion that these antibodies are immune in nature made an in-vivo experiment to determine the clinical significance of the CDAA necessary, for it is conceivable that a situation in which a patient having such antibodies might urgently require albumin therapy might arise. Since all commercially prepared human albumin contains caprylate, administration of this blood derivative would be tantamount to transfusion of an incompatible antigen. The question then was how safe or how dangerous the interaction in vivo of the CDAA with its specific antigen, the caprylate-stabilized human albumin (CSHA), would be. Encouraged by the fact that some molecular antigen-antibody interactions result in no harmful effect, we decided to take advantage of the availability of a normal donor who had CDAA to conduct an ex-
65
periment to answer this question. Other considerations included the fact that the answer to this question could be a matter of life or death for certain patients, including the donor himself should he in the future need albumin therapy. Furthermore, there is no report in the literature on the clinical significance of these antibodies vis-a-vis administration of CSHA. Materials and Methods A normal donor whose serum contained CDAA kindly gave consent for an experimental protocol including the administration to him of 50 ml. of 25% CSHA. Before it was administered, the CSHA was tested to insure that it was active in vitro. The test consisted of two drops of the donor's serum, one drop of 4% saline-suspended cells, and three drops of the 25% CSHA in lieu of 22% bovine albumin. T h e tests were run using cell suspensions from four randomly selected donors as well as that of the subject donor. These cell-serum-albumin mixtures were prepared in duplicate, and all were incubated for 30 minutes at 37 C. One set of tubes was centrifuged and read microscopically for agglutination. After incubation, the second set of tubes was subjected to Coombs' testing. All cells, including those of the subject donor, were agglutinated directly by the albumin test and by the indirect Coombs' technic. Samples of urine and blood were collected prior to administration of CSHA to determine basal hematologic, immunohematologic, hemostatic, immunologic and biochemical values. Similarly, the basal pulse rate, blood pressure, respiratory rate and temperature were recorded. T h e latter were measured twice, with the last measurements made just before the start of the albumin administration. Intravenous administration of albumin was started at the slow rate of 1.0 ml. per min. After 15 minutes, albumin administration was temporarily halted and new blood samples were
Downloaded from http://ajcp.oxfordjournals.org/ by guest on June 7, 2016
reported, shortly thereafter, a more precise mechanism of antibody production. Their studies led to the conclusion that the albumin-agglutinating phenomenon was an immunologic reaction due to an antibody directed at a conformational determinant of commercial albumin and imparted to it by treatment with caprylate or acetyltryptophan. The resultant antigen-antibody complexes cause agglutination of erythrocytes by nonspecific adsorption onto their surfaces. They further speculated that individuals who have the serum agglutinins develop them through the ingestion of food containing sodium caprylate. The ingested caprylate binds to native albumin, resulting in the formation of a new antigenic determinant, namely, caprylate-bound albumin. In susceptible individuals, the caprylate-bound albumin results in the formation of specific antibodies, which for obvious reasons have been termed "caprylate-dependent albumin antibodies" (CDAA). Findings in vitro have strongly supported this theory. However, experimental studies to prove that the proposed mechanism is correct are still lacking.
A.J.C.P.—Vol.
April 1976
515
INDUCTION OF CAPRYLATF7ALBUMIN ANTIBODIES
Results T h e subject expressed no complaint and felt well during the entire observation period. During the infusion period, he demonstrated no apprehension, was relaxed, and conversed normally, indicating complete absence of physical findings of a transfusion reaction. Furthermore, during albumin administration, systolic and diastolic blood pressures, radial pulse, respiratory rate, and temperature, as indicated in Figure 1, showed only minor variations from the corresponding basal levels. On subsequent weekly visits, the subject denied feeling any ill effect as a result of the experiment. Biochemical findings, using the Technicon SMA-12/60 and SMA-6/60, showed only insignificant differences between laboratory values before and after infusion. The levels of serum proteins and of immunoglobulins G, M and A varied only slightly, reflecting minimal changes throughout the experimental period. Hematologic indices, including plasma hemoglobin and all cellular elements, remained almost stationary. Pre- and post-
160 150 h er
140
r
130
e
100
E
90 80
1
70 60
albumin infusion rate infusion increase to started 2 dl/min. rate IdVmln.
•
•
• •
•
• •
SYSTOLIC DIASTOLIC
• • • • J
• •
i_
• •
50 25 20 15
0 15 30 45 60 TIME OF RECORDING IN MINUTES FIG. 1. Blood pressure, radial pulse and respiratory rate 15 minutes before and during albumin infusion.
infusion levels of coagulation factors I, V, VII, VIII, and X, as well as prothrombin time and activated partial thromboplastin time, showed insignificant differences. Routine urinalysis and tests for hemoglobin in the pre- and postinfusion samples disclosed no abnormality. Titers of CDAA in pre- and postinfusion serum samples were determined by serial doubledilution titer using saline solution as diluent. Titers were determined by both albumin and albumin converted to Coombs methods. Identical titers were obtained using the two methods. The results are given in Table 1. Two results were expected, but neither materialized. First, CDAA were expected to decline in titer in the 15-ml.-CSHA and 50-ml.-CSHA samples due to neutralization. Second, a rise in titer in either the one-week or the two-week postinfusion sample, or both, due to an anamnestic response was anticipated. It is obvious from Table 1 that no such change
Downloaded from http://ajcp.oxfordjournals.org/ by guest on June 7, 2016
collected. Administration of the remainder of the CSHA was resumed at the rate of 2.0 ml. per min. Five minutes after the last drop of albumin was administered, new blood and urine samples were collected. The subject was under continual surveillance during the entire experimental period and for an additional 90 minutes after albumin administration was completed. Pulse rate, blood pressure, respiratory rate, and temperature were measured periodically during albumin administration and recorded. Furthermore, the subject was periodically questioned and asked to report any emotional change, ache or pain. Before being discharged, he was asked to report weekly for the next two weeks for questioning and for collection of blood samples.
516
A.J.C.P.—Vol.
HOSSAINI, WASSERMAN, AND VENNART
65
Table 1. Titration Results of Donor's Serum Serum dilution Serum Sample
Undiluted
1:2
1:4
Before albumin infusion After infusion of 15 ml. After infusion of 50 ml. 1 week after infusion 2 weeks after infusion
+++ +++ +++ +++ +++
+++ +++ ++ +++ +++
++ ++ ++ ++ ++
occurred, since the titers remained constant throughout.
1:32
1:64
1:128
body reactions, in-vivo reactions between the CDAA and CSHA would turn out to be harmless. This hope was realized, since administration of 25% CSHA produced no ill effect in the volunteer either during or for a long time after the experiment. At no time did he complain of any ache or pain. In fact, he remained alert and cheerful throughout the experiment. There was no increase in temperature, chill, hypotension, or the appearance of hives or urticaria. There was no hemoglobinemia, hematuria, bilirubinemia, or any sign of coagulopathy. These laboratory findings, together with the physical findings, indicated that the volunteer did not experience any type of transfusion reaction: allergic, febrile, hemolytic or anaphylactoid. Thus, this experiment strongly suggests that CDAA are innocuous, and that administration of albumin to patients who have these antibodies is likely to be devoid of danger.
Following publication of a report on 11 patients with the autoagglutinating phenomenon, 2 we studied the charts of those patients, at the suggestion of Doctor B. P. L. Moore, of the Canadian National Red Cross. This retrospective study revealed that two of the 11 patients had each received several units of CSHA without untoward reaction attributable to the administration of albumin. Thus, it may be assumed that over the years many patients with undetected CDAA have received albumin therapy. Nevertheless, the lack of definite evidence for the innocuous nature of these antibodies made experimental support of its safety mandatory. It must also be realized that the rarity of the phenomenon and the nature of the experiment severely limit the opportunities to carry out It is appropriate to mention that clinical such a detailed experiment. Thus, al- experience has provided ample evidence though the conclusions presented here are for the safety of administering whole blood those based on the results of a single to such patients despite strong incompatiexperiment, they should not be taken bility in the albumin phase of the crosslightly. That the donor's serum contained match. The safety of administering whole two forms (direct-reacting and indirect- blood could be easily explained. Golde, reacting) of the antibody, both of which McGinnis and Holland 1 brilliantly demonreacted only at body temperature, en- strated that an essential ingredient of cell hances the significance of this experiment, clumping by CDAA is the presence of since antibodies that react at 37 C. are con- sodium caprylate. Since no such compound sidered more dangerous than those that is added to blood before it is transfused, react at lower temperatures. Nevertheless, no clumping of the cells should occur. the experiment was conducted with the Therefore, once the agglutination of crosshope that, like some other antigen-anti- matched donor erythrocytes in the pres-
Downloaded from http://ajcp.oxfordjournals.org/ by guest on June 7, 2016
Discussion
1:16
April 1976
INDUCTION OF CAPRYLATE/ALBUMIN ANTIBODIES
In conclusion, a normal donor who had the caprylate-dependent albumin agglutinins volunteered to receive 50 ml. of 25% caprylate-stabilized human albumin to determine the clinical significance of the antibodies. T h e subject manifested no clinical sign of a reaction. Samples of blood and urine collected before, during, and after administration of albumin were subjected to extensive laboratory investigation. All biochemical, immunologic, hematologic, hemostatic and immunohematologic values investigated showed only insignificant variations. These results indicate that infusion of albumin was safe, for there was no hemolytic, febrile, allergic, or anaphylactic transfusion reaction. This experiment is the only one of its kind, so caution is needed when administering albumin to a patient who has CDAA until sufficient experiments confirm the complete safety of such a transfusion. References 1. Golde DW, McGinnis MH, Holland PV: Mechanism of the albumin agglutination phenomenon. Vox Sang 16:465-469, 1969 2. Hossaini AA: Effects of albumin concentration on compatibility tests for blood transfusion. Am J Clin Pathol 36:348-351, 1966 3. Lovett CA, Moore BPL: Pan and autoagglutination in albumin: A serological and immunochemical study of five cases. J Immunol 14: 3 5 7 - 3 6 5 , 1968 4. Weinei- VV, Tovey GH, Gillespie HBM, et al: Albumin autoagglutinating property in three sera. A pitfall for the unwary. Vox Sang 1: 279-288, 1956
Downloaded from http://ajcp.oxfordjournals.org/ by guest on June 7, 2016
ence of albumin has been established to be solely due to the presence of CDAA in the patient's serum, the cells could be released to the patient without hesitation. In contrast, in the case of albumin therapy for a patient having CDAA, one is confronted with a decision that involves the advisability of transfusing CSHA which, in fact, amounts to administering an incompatible antigen. In our view, if a patient badly needs albumin, it should be administered. Caution must be exercised, however, since experience with the safety of this procedure is meager. T h e results of this experiment and our retrospective studies leading to the discovery of two patients who had inadvertantly received albumin lead us to suggest that initially the rate of administration should be slow, not exceeding 1 ml. per min. for the first 15 minutes. Should a reaction attributable to the infusion occur, the infusion should be halted immediately and appropriate therapy instituted. In the absence of a reaction, the rate of administration could be increased, provided again the patient is kept under surveillance for late signs of a reaction. Since additional clinical data are essential to establish the safety of this practice on a more firm basis, it is essential that these experiences be made available in the literature. An accumulation of such data will, we hope, confirm that administering albumin to patients with CDAA is safe, and that it could be administered as fast as needed.
517
AND GEORGE P. VENNART, M.D.
From the Department of Pathology and Department of Pharmacology, Medical College of Virginia, Virginia Commonwealth University, Richmond, Virginia
ABSTRACT
IN 1956, Weiner and associates4 reported the finding of three sera each of which strongly agglutinated all human cells ineluding their own only when the cells were suspended in an albumin medium, Over the years that followed, many examples of this serologic idiosyncrasy were re-
ported. Attempts were made to determine the nature of these agglutinins and the mechanism by which they agglutinated erythrocytes. Studies by Lovett and colleagues 3 and by Golde and co-workers' suggested that the phenomenon was immune in nature. T h e studies of Lovett and Moore 3 led to the postulate that the agglutinating factor was an antibody
; Received March 31, 1975; received revised manu-
••
•
•
,
•
c
script June 30, 1975; accepted for publication June 30, 1975.
directed against a minor determinant of some bovine serum albumins that formed
Presentedatthe27thAnnualMeeting0ftheAmencan Association or Blood Banks, November 9 - 1 4 ,
s o
1974, Anaheim, California.
Address reprint requests to Dr. Hossaini: Director of the School of Blood Banking, Medical College of Virginia, 1200 East Broad Street, Richmond, Virginia
23298.
,uble
ant
j g e r ) - a n t i b o d y complexes. Be° / r
cause of steric configuration, these cornp l e x e s n o n s p e c i f i c a l l y a d s o r b o n t o t h e SU1, . , , r of erythrocytes, causing them to dump1
r f a c e
in vitro. Golde, McGinnis and Holland
513
Downloaded from http://ajcp.oxfordjournals.org/ by guest on June 7, 2016
Hossaini, Ali A., Wasserman, Albert J., and Vennart, George P.: Experimental induction of caprylate-dependent albumin antibodies. Am J Clin Pathol 65: 513-517, 1976. A normal donor with the caprylate-dependent albumin agglutinins volunteered to receive 50 ml. of 25% caprylate-stabilized human albumin to determine the clinical significance of the antibodies. The donor manifested no clinical sign of a reaction. Samples of blood and urine collected before, during and after administration of albumin were subjected to extensive laboratory investigation. Biochemical, immunologic, hematologic, hemostatic and immunohematologic variables investigated showed only insignificant variations in all blood and urine samples. Results indicated that the infusion of albumin was safe, for the donor showed no sign of a hemolytic, febrile, allergic or anaphylactic transfusion reaction. However, since this is the first and only reported experiment of its kind, it is deemed advisable to exercise caution when administering albumin to patients who have caprylate-dependent albumin agglutinins until sufficient supportive data attesting to the complete safety of this procedure have accumulated. (Key words: Transfusion; Albumin; Antibodies; Transfusion reaction; Sodium caprylate; Caprylatestabilized albumin; Caprylate-dependent albumin agglutinins; Albumin autoagglutinins.)
514
HOSSAINI, WASSERMAN, AND VENNART
T h e suggestion that these antibodies are immune in nature made an in-vivo experiment to determine the clinical significance of the CDAA necessary, for it is conceivable that a situation in which a patient having such antibodies might urgently require albumin therapy might arise. Since all commercially prepared human albumin contains caprylate, administration of this blood derivative would be tantamount to transfusion of an incompatible antigen. The question then was how safe or how dangerous the interaction in vivo of the CDAA with its specific antigen, the caprylate-stabilized human albumin (CSHA), would be. Encouraged by the fact that some molecular antigen-antibody interactions result in no harmful effect, we decided to take advantage of the availability of a normal donor who had CDAA to conduct an ex-
65
periment to answer this question. Other considerations included the fact that the answer to this question could be a matter of life or death for certain patients, including the donor himself should he in the future need albumin therapy. Furthermore, there is no report in the literature on the clinical significance of these antibodies vis-a-vis administration of CSHA. Materials and Methods A normal donor whose serum contained CDAA kindly gave consent for an experimental protocol including the administration to him of 50 ml. of 25% CSHA. Before it was administered, the CSHA was tested to insure that it was active in vitro. The test consisted of two drops of the donor's serum, one drop of 4% saline-suspended cells, and three drops of the 25% CSHA in lieu of 22% bovine albumin. T h e tests were run using cell suspensions from four randomly selected donors as well as that of the subject donor. These cell-serum-albumin mixtures were prepared in duplicate, and all were incubated for 30 minutes at 37 C. One set of tubes was centrifuged and read microscopically for agglutination. After incubation, the second set of tubes was subjected to Coombs' testing. All cells, including those of the subject donor, were agglutinated directly by the albumin test and by the indirect Coombs' technic. Samples of urine and blood were collected prior to administration of CSHA to determine basal hematologic, immunohematologic, hemostatic, immunologic and biochemical values. Similarly, the basal pulse rate, blood pressure, respiratory rate and temperature were recorded. T h e latter were measured twice, with the last measurements made just before the start of the albumin administration. Intravenous administration of albumin was started at the slow rate of 1.0 ml. per min. After 15 minutes, albumin administration was temporarily halted and new blood samples were
Downloaded from http://ajcp.oxfordjournals.org/ by guest on June 7, 2016
reported, shortly thereafter, a more precise mechanism of antibody production. Their studies led to the conclusion that the albumin-agglutinating phenomenon was an immunologic reaction due to an antibody directed at a conformational determinant of commercial albumin and imparted to it by treatment with caprylate or acetyltryptophan. The resultant antigen-antibody complexes cause agglutination of erythrocytes by nonspecific adsorption onto their surfaces. They further speculated that individuals who have the serum agglutinins develop them through the ingestion of food containing sodium caprylate. The ingested caprylate binds to native albumin, resulting in the formation of a new antigenic determinant, namely, caprylate-bound albumin. In susceptible individuals, the caprylate-bound albumin results in the formation of specific antibodies, which for obvious reasons have been termed "caprylate-dependent albumin antibodies" (CDAA). Findings in vitro have strongly supported this theory. However, experimental studies to prove that the proposed mechanism is correct are still lacking.
A.J.C.P.—Vol.
April 1976
515
INDUCTION OF CAPRYLATF7ALBUMIN ANTIBODIES
Results T h e subject expressed no complaint and felt well during the entire observation period. During the infusion period, he demonstrated no apprehension, was relaxed, and conversed normally, indicating complete absence of physical findings of a transfusion reaction. Furthermore, during albumin administration, systolic and diastolic blood pressures, radial pulse, respiratory rate, and temperature, as indicated in Figure 1, showed only minor variations from the corresponding basal levels. On subsequent weekly visits, the subject denied feeling any ill effect as a result of the experiment. Biochemical findings, using the Technicon SMA-12/60 and SMA-6/60, showed only insignificant differences between laboratory values before and after infusion. The levels of serum proteins and of immunoglobulins G, M and A varied only slightly, reflecting minimal changes throughout the experimental period. Hematologic indices, including plasma hemoglobin and all cellular elements, remained almost stationary. Pre- and post-
160 150 h er
140
r
130
e
100
E
90 80
1
70 60
albumin infusion rate infusion increase to started 2 dl/min. rate IdVmln.
•
•
• •
•
• •
SYSTOLIC DIASTOLIC
• • • • J
• •
i_
• •
50 25 20 15
0 15 30 45 60 TIME OF RECORDING IN MINUTES FIG. 1. Blood pressure, radial pulse and respiratory rate 15 minutes before and during albumin infusion.
infusion levels of coagulation factors I, V, VII, VIII, and X, as well as prothrombin time and activated partial thromboplastin time, showed insignificant differences. Routine urinalysis and tests for hemoglobin in the pre- and postinfusion samples disclosed no abnormality. Titers of CDAA in pre- and postinfusion serum samples were determined by serial doubledilution titer using saline solution as diluent. Titers were determined by both albumin and albumin converted to Coombs methods. Identical titers were obtained using the two methods. The results are given in Table 1. Two results were expected, but neither materialized. First, CDAA were expected to decline in titer in the 15-ml.-CSHA and 50-ml.-CSHA samples due to neutralization. Second, a rise in titer in either the one-week or the two-week postinfusion sample, or both, due to an anamnestic response was anticipated. It is obvious from Table 1 that no such change
Downloaded from http://ajcp.oxfordjournals.org/ by guest on June 7, 2016
collected. Administration of the remainder of the CSHA was resumed at the rate of 2.0 ml. per min. Five minutes after the last drop of albumin was administered, new blood and urine samples were collected. The subject was under continual surveillance during the entire experimental period and for an additional 90 minutes after albumin administration was completed. Pulse rate, blood pressure, respiratory rate, and temperature were measured periodically during albumin administration and recorded. Furthermore, the subject was periodically questioned and asked to report any emotional change, ache or pain. Before being discharged, he was asked to report weekly for the next two weeks for questioning and for collection of blood samples.
516
A.J.C.P.—Vol.
HOSSAINI, WASSERMAN, AND VENNART
65
Table 1. Titration Results of Donor's Serum Serum dilution Serum Sample
Undiluted
1:2
1:4
Before albumin infusion After infusion of 15 ml. After infusion of 50 ml. 1 week after infusion 2 weeks after infusion
+++ +++ +++ +++ +++
+++ +++ ++ +++ +++
++ ++ ++ ++ ++
occurred, since the titers remained constant throughout.
1:32
1:64
1:128
body reactions, in-vivo reactions between the CDAA and CSHA would turn out to be harmless. This hope was realized, since administration of 25% CSHA produced no ill effect in the volunteer either during or for a long time after the experiment. At no time did he complain of any ache or pain. In fact, he remained alert and cheerful throughout the experiment. There was no increase in temperature, chill, hypotension, or the appearance of hives or urticaria. There was no hemoglobinemia, hematuria, bilirubinemia, or any sign of coagulopathy. These laboratory findings, together with the physical findings, indicated that the volunteer did not experience any type of transfusion reaction: allergic, febrile, hemolytic or anaphylactoid. Thus, this experiment strongly suggests that CDAA are innocuous, and that administration of albumin to patients who have these antibodies is likely to be devoid of danger.
Following publication of a report on 11 patients with the autoagglutinating phenomenon, 2 we studied the charts of those patients, at the suggestion of Doctor B. P. L. Moore, of the Canadian National Red Cross. This retrospective study revealed that two of the 11 patients had each received several units of CSHA without untoward reaction attributable to the administration of albumin. Thus, it may be assumed that over the years many patients with undetected CDAA have received albumin therapy. Nevertheless, the lack of definite evidence for the innocuous nature of these antibodies made experimental support of its safety mandatory. It must also be realized that the rarity of the phenomenon and the nature of the experiment severely limit the opportunities to carry out It is appropriate to mention that clinical such a detailed experiment. Thus, al- experience has provided ample evidence though the conclusions presented here are for the safety of administering whole blood those based on the results of a single to such patients despite strong incompatiexperiment, they should not be taken bility in the albumin phase of the crosslightly. That the donor's serum contained match. The safety of administering whole two forms (direct-reacting and indirect- blood could be easily explained. Golde, reacting) of the antibody, both of which McGinnis and Holland 1 brilliantly demonreacted only at body temperature, en- strated that an essential ingredient of cell hances the significance of this experiment, clumping by CDAA is the presence of since antibodies that react at 37 C. are con- sodium caprylate. Since no such compound sidered more dangerous than those that is added to blood before it is transfused, react at lower temperatures. Nevertheless, no clumping of the cells should occur. the experiment was conducted with the Therefore, once the agglutination of crosshope that, like some other antigen-anti- matched donor erythrocytes in the pres-
Downloaded from http://ajcp.oxfordjournals.org/ by guest on June 7, 2016
Discussion
1:16
April 1976
INDUCTION OF CAPRYLATE/ALBUMIN ANTIBODIES
In conclusion, a normal donor who had the caprylate-dependent albumin agglutinins volunteered to receive 50 ml. of 25% caprylate-stabilized human albumin to determine the clinical significance of the antibodies. T h e subject manifested no clinical sign of a reaction. Samples of blood and urine collected before, during, and after administration of albumin were subjected to extensive laboratory investigation. All biochemical, immunologic, hematologic, hemostatic and immunohematologic values investigated showed only insignificant variations. These results indicate that infusion of albumin was safe, for there was no hemolytic, febrile, allergic, or anaphylactic transfusion reaction. This experiment is the only one of its kind, so caution is needed when administering albumin to a patient who has CDAA until sufficient experiments confirm the complete safety of such a transfusion. References 1. Golde DW, McGinnis MH, Holland PV: Mechanism of the albumin agglutination phenomenon. Vox Sang 16:465-469, 1969 2. Hossaini AA: Effects of albumin concentration on compatibility tests for blood transfusion. Am J Clin Pathol 36:348-351, 1966 3. Lovett CA, Moore BPL: Pan and autoagglutination in albumin: A serological and immunochemical study of five cases. J Immunol 14: 3 5 7 - 3 6 5 , 1968 4. Weinei- VV, Tovey GH, Gillespie HBM, et al: Albumin autoagglutinating property in three sera. A pitfall for the unwary. Vox Sang 1: 279-288, 1956
Downloaded from http://ajcp.oxfordjournals.org/ by guest on June 7, 2016
ence of albumin has been established to be solely due to the presence of CDAA in the patient's serum, the cells could be released to the patient without hesitation. In contrast, in the case of albumin therapy for a patient having CDAA, one is confronted with a decision that involves the advisability of transfusing CSHA which, in fact, amounts to administering an incompatible antigen. In our view, if a patient badly needs albumin, it should be administered. Caution must be exercised, however, since experience with the safety of this procedure is meager. T h e results of this experiment and our retrospective studies leading to the discovery of two patients who had inadvertantly received albumin lead us to suggest that initially the rate of administration should be slow, not exceeding 1 ml. per min. for the first 15 minutes. Should a reaction attributable to the infusion occur, the infusion should be halted immediately and appropriate therapy instituted. In the absence of a reaction, the rate of administration could be increased, provided again the patient is kept under surveillance for late signs of a reaction. Since additional clinical data are essential to establish the safety of this practice on a more firm basis, it is essential that these experiences be made available in the literature. An accumulation of such data will, we hope, confirm that administering albumin to patients with CDAA is safe, and that it could be administered as fast as needed.
517
