TRANSFUSION I983-Vol. 23. No. 4 CORRESPONDENCE 363

References 1. Heaton DC. McLoughlin K. Jk(a-b-) red blood cells resist urea

lysis. Transfusion 1982;2270-1. 2. Mitui M. Uchiyama E, Kikuchi M, etal. First Japaneseexample

of rare blood phenotype Jk(a-b-) and incidence of the pheno- type in Japanese population. Abstract of papers presented at the 27th congress Japanese Society for Human Genetics 198251 (in Japanese).

Pamive mti-D from Intravenous immune serum globulin To the Edltor:

i n 1971 we reported red cell sensitization resulting from administration of intramuscular immune serum globulin.' The presence of high-titer anti-D in such preparations may cause difficulty in serologic assessment of patients, and may result in undue expenditure of laboratory resources to clarify problems. An Rh positive patient may present with a positive direct antiglobulin test and eluate, and a n Rh negative patient may have a positive serum antibody screening test due to the passively acquired antibody. The only requirement for licensure of immune serum globulin relates to the content of globulin. There are no standards concerning the maximum amount of other materials, such as blood group antibodies in such preparations.

We recently encountered a relevant problem related to administration of intravenous immune serum globulin: A 30-year-old man, hospitalized for refractory idiopathic thrombocytopenia, was treated with intravenous immune serum globulin, 24 g per day for 4 days. On the third day the patient's red cells manifested a positive direct antiglobulin test and anti-D was demonstrated in a n ether eluate.

Subsequent investigation revealed that the patient was Rh positive and that the source of this antibody was the intravenous immune serum globulin. No free antibody was present in the patient's serum, and the hemoglobin remained unchanged during the 4days following administration of the material.

The titer of anti-D in the immune serum globulin preparation, by saline-antiglobulin technic, was 128. The patient did not appear to have any adverse clinical sequelae from this material.

As noted in our previous report, as well as in a Letter to the Editor of the New England Journol of Medicine published in the same year: these antibodies in immune serum globulin may confuse and complicate serologic testing of transfusion candidates.

ELIZABETH A. STEINER, MT(ASCP)SBB SUZANNE H. BUTCH, MT(ASCP)SBB

JOHN L. CAREY, M D HAROLD A. OBERMAN, M D

Blood Bonk, Deportment of Pathology University of Michigon Hospitols

Ann Arbor, MI 48109

References I . Oberman HA, Beck ML. Red blood cell sensitization due to

unexpected Rh antibodies in immune serum globulin. Transfu- sion 1971;l 1:3824.

2. Niosi P, Lundberg J. McCullough J, Park BH, Biggar DW. Blood group antibodies in human immune serum globulin. New Engl J Med 1971;285:1435-6.

S u c c d d cardiac bypass surgery in the presence of 8 potent cold agglutinin without plunu cxchnge

To the Editor: Systemic hypothermia and cold cardioplegia are com-

monly used in cardiac surgery employing extracorporeal circulation of the blood.' The use of cold cardioplegia to preserve the heart uniformly is believed critical for preven- tion of ischemic myocardial damage during prolonged cardiac bypass. Temperatures in both the extracorporeal and coronary circulations may reach 15°C or below. This has led to concern over normally inconsequential, high-titer, broad-thermal-range cold autoagglutinins. Some have ad- vocated intensive preoperative plasma exchange to reduce the theoretical risks of in vivo agglutination and/or hemolysis.' We report here an alternative procedure.

Our patient, a 61-year-old man requiring triple coronary artery bypass, had a cold autoagglutinin with anti-i specificity. In two different laboratories, titers of up to 8 a t 37"C, 4 a t 30". 64 a t room temperature, and 2048 at 4" were observed. No laboratory or clinical signs of cold agglutinin disease or cold autoimmune hemolytic anemia were present. In a n impromptu, but controlled, test of the potential for spontaneous in vivo agglutination, his heparinized whole blood at 37°C was mixed 1:2 with 4°C saline on a slide. Macroscopic agglutination (4+) occurred within 30 seconds. This suggested the possibility that a similar phenomenon might occur in the coronary circulation when the 4°C cardioplegic solution was injected. Plasma exchange to lower the cold agglutinin titer was not feasible, and surgery was considered urgent.

To avoid potential agglutination in the general circula- tion, systemic hypothermia was not employed. However it was necessary to employ cold cardioplegia in the coronary circulation. A clear, potassiumcontaining cardioplegic solution was used. Before introduction of 4°C cardioplegic solution into the aortic root, 37OC solution was used as a flush. Cardioplegia was then maintained by infusion of 4" C solution for the 1.6 hours of cardiopulmonary bypass. Before reintroduction of blood into the chilled heart after bypass, a 37°C cardioplegic solution flush was administered. The patient required one unit of red cells intraoperatively and made an uneventful recovery. No evidence of in vivo agglutination or hemolysis was found.

The need for plasma exchange prior to cardiac surgery in patients with potent cold agglutinins remains unproven. However, the procedure described here, when surgically feasible, requires n o delay in surgery, no risk of hemostatic imbalance or hepatitis, and is minimal in expense compared with plasma exchange. A similar patient, whose cold agglutinin was nonreactive at 32OC, recently was treated successfully by Dr. Berreklouw and colleagues.' Our findings suggest that even patients with antibodies reactive a t 37°C can be managed in this manner.

NEIL BLUMBERG, M D GEORGE HICKS, M D JUDITH WOLL, M D

JACOB NUSBACHER, M D MARY T. Cox, MT(ASCP)SBB

DONNA SCHWEDFEGER, MT(ASCP) ANN MCMICAN, MT(ASCP)SBB

University of Rochester Medico1 Center Rochester, N Y 14642

American Red Cross Blood Services Rochester, N Y 14607

DAVID WILBUR, M D

364 CORRESPONDENCE TRANSFUSION Vol. 23, No. 4-1983

References 1. Papper S, Williams GR. eds. Manual of medical care of the

surgical patient. 2nd ed. Boston: Little, Brown, 1981:21-3. 2. Klein HG. Kaltz LL, Mclntosh CL, Appelbaum FR, Deis-

seroth AB, Holland PV. Surgical hypothermia in a patient with a cold agglutinin - management by plasma exchange. Transfu- sion 1980;20354-7.

3. Berreklouw E. Moulijn AC, Pegels JG, Meijne NG. Myocardial protection with cold cardioplegia in a patient with cold autoag- glutinins and hemolysins. Ann Thorac Surg 1982;33:521-2.

Heterogeneity of U antibodies To the Editor:

In a letter to the editor of a recent issue of TRANSFUSION, Beattie et al.' emphasize the importance of identifying U"' donors by adsorption-elution techniques before transfusing blood to patients with sickle cell anemia having anti-U. The purpose of taking these added precautions was to prevent broadening of the anti-U specificity that will become evident by subsequent sensitization of crossmatch-compatible trans- fused red cells.

Heterogeneity of U antibodies has been reported on the basis of different percentages of nonreactive samples obtained with individual examples of anti-U when testing red cells of black populations. Possible "mosaicism" similar to Rh, has been postulated.* We report a n additional case, similar to the one described by Beattie, of a n all0 anti-U causing in vivo sensitization of apparently U-negative trans- fused red cells.

A previously transfused, 58-year-old, gravida 0, woman was admitted with a diagnosis of chronic lymphocytic leukemia and anemia. Pretransfusion tests showed a negative direct antiglobulin test (DAT), positive antibody screen, and reactivity with all ABO compatible donors a t the antiglobulin test phase. Anti-U was identified in the patient's serum reacting with 20 U-positive red cell samples and nonreactive with five U negatives. The patient's pretransfu- sion red cells did not react with four examples of anti-U and were S-negative and s-negative.

The patient was transfused with 10 units of red cells from 2-1-81 through 4-24-8 1 (Table I). The presence ofanti-U and the absence of additional antibody specificities was con-

firmed with each sample received for pretransfusion testing until 4-22-81. when allo anti-E was detected in addition to the anti-U. Only two of the 19 units transfused (given 2-3-81 and 3-21-81) were from donors known t o be E-positive. All units transfused subsequently were E-negative and U-nega- tive. Each time compatibility testing was performed prior to 4-29-81, the auto control and the DAT were negative. All 10 units were found to be U-negative by the blood supplier, and were crossmatch-compatible with the patient's serum prior to transfusion. Pretransfusion testing for subsequent units showed a weakly positive mixed field D A T due to IgG persisting for 5 weeks after initial observation. Ether eluates from these cells contained only anti-U.

We postulate that this patient had a delayed hemolytic transfusion reaction. Our assumption is based on the mixed- field positive DAT, anti-U recovered in the eluate, and a twofold increase in the transfusion requirement as compared to the initial phases of therapy. The patient's reaction was the result of a sensitizing antibody different from the initial specificity and formed in response to one o r more of the apparently U-negative units transfused prior to 4-29-81. The unit (or units) of red cells was probably what Beattie refers to as the U"' phenotype, causing an immune response and showing heterogeneity of U blood group antigens and antibodies based on in vivo sensitization. Unfortunately, we were unable to support our serologic findings by adsorption- elution or by reacting postsensitization serum samples with donor red cells due to our inability to procure additional blood samples from the donors transfused to the patient. The patient died on 6-13-81 due to multiple complications resulting from the leukemia.

CATHERINE MICELI, MT(ASCP)SBB ULRlCH DIEKAMP, M D

STEVEN D. SOSLER, MS, SBB(ASCP) University of Illinois at Chicago

Health Sciences Center, Chicago, IL

References I . Beattie KM, Sigmund KE, McGraw J. Shurafa M. U-variant

2. lssitt PD, lssitt CH. Applied blood group serology. 2nd ed. Ox- blood in sickle cell patients. Transfusion 1982;22257.

nard, CA: Spectra Biologicals, 1975; 187.

Table 1. Transfusion and serologic history of patient

Patient Patient Patient Number of anti body anti body anti body RBC units Date screen specificity Pati en t specificity transfused transfused (AGT) (serum) t (eluate)

Preantibody 2 2

Postantibody 1 2 3 2 2

Postsensitization 2 3

9-1 2-80 9-1 4-80 2-1-81 2-2-81 3-21-81 3-30-81 4-24-81

4-29-81 5-21-81

0 0

4+ 4+ 4+ 4+ 4+

4+ 4+

0 0

Anti-U 0 Anti-U 0 Ant i4 0 Anti-U 0 Anti-U and anti-E 0 Anti-U and anti-E +w m.f. * Anti-U Anti-U and anti-E +w m.f.$ Anti-U

= Antiglobulin test phase t = Direct antiglobulin test $ = Mixed-field agglutination