Cold Agglutinins. I. Occurrence of Cold Isohemagglutinins in Various Conditions

Finland, Maxwell; Peterson, Osler L.; Allen, Howard E.; Samper, Bernardo A.; Barnes, Mildred W.; Stone, Muriel B.

doi:10.1172/jci101623

Cited by 63 publications

(13 citation statements)

References 14 publications

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“…A few sera which were obtained from 3 of the patients with acute hemolytic anemia (5) are also included.…”

Section: Methodsmentioning

confidence: 99%

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Cold Agglutinins. V. Deterioration of Cold Isohemagglutinins on Storage

Finland¹,

Barnes²

1945

J. Clin. Invest.

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When the first instances of marked cold hemagglutination were noted in this laboratory in cases of primary atypical pneumonia of unknown etiology (1), a number of sera were available from other similar cases which had been studied during the preceding months. Most of these sera had been obtained from cases in this hospital but many were from other hospitals. The large majority of them gave negative results when tested for cold agglutinins. On the other hand, sera from characteristic cases obtained at the proper time in the course of the disease from patients who were being currently observed gave positive results.Several possible explanations for this discrepancy were considered. In the first place, it was possible that the earlier cases differed from the current ones with respect to the occurrence of cold agglutinins. This explanation seemed unlikely in view of the similarity of the clinical course in both groups of cases. It seemed possible, however, that variations in severity of the cases might have accounted for the differences. The earliest cases in which the cold agglutinins were observed were very severe ones and many of the others that were being encountered at that time seemed to be of greater severity than those which had been described from schools and from military hospitals. Many of the sera which had been stored were from mild cases in young adults and some of them were from military hospitals. Interestingly enough, most of the few positive results among the stored sera were from very severe cases in which there was extensive pulmonary involvement (2).Another possible explanation depended on the likelihood that most of the sera that were stored had been improperly prepared and preserved. It is usually more convenient to collect a number of specimens of blood, store them in a refrigerator over night, and take off the serum on the following day. The possibility must, therefore, be considered that, without special precautions having been taken to warm the bloods, some at least of the cold agglutinins might have been adsorbed on the red blood cells of the clot and left behind in the process of taking off the serum. Such a loss can readily be demonstrated, particularly if the blood remains cold while the serum is rapidly removed. For the most part, however, the bloods were kept at room temperature for some time before the sera were separated. Subsequent observations have indicated that under the latter circumstances very little drop in the titer of cold agglutinins occurs.Finally, the possibility was considered that the cold agglutinins had deteriorated on storage. This was suggested by other workers (3) to explain the low titers of some of the stored sera from characteristic cases of atypical pneumonia in their series. In another study (4), more than onethird of the sera had been stored for several months although it is not stated what proportion of the negative sera in cases of atypical pneumonia were among those which had been stored. Alternative explanations were given by the latter authors for mos...

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“…A few sera which were obtained from 3 of the patients with acute hemolytic anemia (5) are also included.…”

Section: Methodsmentioning

confidence: 99%

“…The method used for determining the titer of cold agglutinins was described in a previous paper (5 were 486 repeat test of the 248 sera and these formed the basis of the analysis which follows.…”

Section: Methodsmentioning

confidence: 99%

Cold Agglutinins. V. Deterioration of Cold Isohemagglutinins on Storage

Finland¹,

Barnes²

1945

J. Clin. Invest.

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“…The method used in the tests for cold agglutins was given in detail in the preceding paper (1). For the present study, the specimens of venous blood were all collected under sterile precautions and the serum was separated from the clotted blood, either at room tempera-1 Hereafter referred to for brevity as "atypical pneumonia."…”

Section: Patients Materials and Methodsmentioning

confidence: 99%

Cold Agglutinins. Ii. Cold Isohemagglutinins in Primary Atypical Pneumonia of Unknown Etiology With a Note on the Occurrence of Hemolytic Anemia in These Cases

Finland¹,

Peterson²,

Allen³

et al. 1945

J. Clin. Invest.

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In the preceding paper ( 1), there was presented a summary of the maximum titers of cold agglutinins found in 1069 cases of a variety of conditions, including the various infections of the respiratory tract that are commonly encountered in this vicinity. Significant titers (in dilutions greater than 20) were Methods. The method used in the tests for cold agglutins was given in detail in the preceding paper (1). For the present study, the specimens of venous blood were all collected under sterile precautions and the serum was separated from the clotted blood, either at room tempera-1 Hereafter referred to for brevity as "atypical pneumonia." ture or, more often, after the blood had been kept at 370 C. for a short while. The cleared sera were stored in rubber stoppered tubes at 5 to 100 C. Specimens, averaging 3 per patient, were obtained at suitable intervals. The tests were carried out either on the day when the blood was obtained or within a few days. Equal volumes of serum and 2 per cent saline suspensions of 2-to 4-day-old red blood cells from individual group 0 donors were used. The titers are recorded as the reciprocals of the highest final dilutions of serum giving 1 + agglutination at 0 to 50 C. and complete dispersion at 370 C. RESULTSThe conditions under which the present cases were studied unfortunately did not permit frequent observations throughout the entire course of the acute illness and prolonged observations during convalescence in every instance. Data concerning certain of the features to be considered are, therefore, based on limited numbers of cases. In the analysis which follows, the time relationships are referred to the day of onset of symptoms. In most of the cases, this could be ascertained quite accurately, but, in a few instances, it was only approximated. Time of appearance, decline, and disappearanceThe first postitive tests ( Figure 1A) were observed between the seventh and twenty-seventh days, but mostly during the second or third week. The last negative tests in the same cases were obtained before the end of the second week in all but 2 of them. The maximum titers (Figure 2) occurred mostly between the eleventh and twentyfourth days. There were a number of cases, however, in which the maximum titers were not attained until the fifth week or later, and in 4 cases, maximum titers of 40 to 160 were observed between the fourth and eighth days and lower titers obtained later. There was no definite correlation between the maximum titers and the time 458

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“…The principal technical aspects of cold agglutinin titration were considered in the classical papers by Finland and his colleagues 25 years ago [1][2][3][4]. All investigators have emphasized the dependence of absolute titra tion values on technical variables (e.g.…”

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confidence: 99%

“…with hypogamma globulinemia who developed severe, acute, autoimmune hemolytic anemia with a strongly positive antiglobulin reaction due to the presence of C'3 and C'4 on her red blood cells. Cold agglutinin titra tion by conventional methods yielded a modest value of 128; the titer in 22% bovine serum 1 Supported by Grant CA 02918 from the National Cancer Institute, NIH. albumin (BSA) was 131,000.…”

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An Enhancing Effect of Albumin on the Determination of Cold Hemagglutinins

Hayes¹,

Chaplin²

1971

Vox Sanguinis

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Serum from a patient with hypogammaglobulinemia was found to have a cold agglutinin titer of 128 when diluted in saline and 131,000 when diluted in 22% bovine serum albumin. Human serum albumin and a non-protein-containing commercial agglutination potentiator had similar enhancing properties. A degree of albumin enhancement of cold agglutination was observed in approximately 25% of normal and patient sera examined. The mechanism of enhancement and the possible clinical significance of the phenomenon are not yet known.

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Cold Agglutinins. I. Occurrence of Cold Isohemagglutinins in Various Conditions

Cited by 63 publications

References 14 publications

Cold Agglutinins. V. Deterioration of Cold Isohemagglutinins on Storage

Cold Agglutinins. V. Deterioration of Cold Isohemagglutinins on Storage

Cold Agglutinins. Ii. Cold Isohemagglutinins in Primary Atypical Pneumonia of Unknown Etiology With a Note on the Occurrence of Hemolytic Anemia in These Cases

An Enhancing Effect of Albumin on the Determination of Cold Hemagglutinins

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