IN VIVO SURVIVAL IN THE HUMAN SUBJECT OF TRANSFUSED ERYTHROCYTES AFTER STORAGE IN VARIOUS PRESERVATIVE SOLUTIONS
Authors: Mollison P. L. , Young I. M. 
Published: December 2014

The results of the commonly accepted in vitro tests, made upon samples of stored blood, are fallacious indicators of the state of preservation of biological activity, as judged by the subsequent in vivo survival of the erythrocytes. In the selection of preservative solutions, however, in vitro tests may have a negative value. For instance, if blood hæmolyses rapidly in a given solution, that solution may safely be rejected. If, however, a solution is found to be successful in inhibiting hæmolysis, it will not necessarily succeed in prolonging in vivo survival.

The degree to which stored erythrocytes resist vigorous shaking in the presence of glass beads is not correlated with their survival time in vivo.

Although the osmotic fragility of stored erythrocytes, as usually measured, has led to many fallacious conclusions as to the value of different blood preservatives, a revised test in which the erythrocytes are first treated with fresh plasma may be found more useful.

The in vivo survival of blood stored without carbohydrate is almost as good as that of fresh blood when the period of storage is 6 days or less. I. H. T., sodium citrate, and heparin all seem to have a similar effect upon subsequent survival; defibrinated blood seems to survive slightly better. In the treatment of anæmia it is suggested that the limit of 6 days is not exceeded when using blood stored in one of these solutions. Blood stored for 14 days without carbohydrate is almost useless to the recipient as a source of biologically active erythrocytes, although it usually does not contain sufficient free hæmoglobin at this time to be actually a source of danger.

Dextrin and sucrose, although they delay the onset of hæmolysis in vitro almost as well as glucose, have very little effect in prolonging the in vivo survival of blood.

The effect of glucose in prolonging the survival of erythrocytes is very definite, and varies with alterations in the amount and concentration of glucose that is added. When approximately one volume of citrate‐glucose solution is added to four volumes of blood, variation of the concentration of glucose in the final mixture from 0·6 to 2·2 per cent, makes little difference to subsequent survival. If a larger volume of citrate‐glucose solution is added, however, and a final concentration of 2·7 per cent. in the final mixture is attained, survival is very definitely prolonged. Thus, whereas blood stored in the standard citrate‐glucose solution (VI) for periods of 11‐15 days already shows some falling off in survival, blood stored with the Rous‐Turner solution (X) for periods up to 21 days has a survival which is very little inferior to that of fresh blood. Although the Rous‐Turner solution is thus a better preservative than the citrate‐glucose solution in general use, the advantage is not obvious with blood stored for less than 10 days at least. Moreover, the large relative volume of diluent in the Rous‐Turner solution is a definite disadvantage both from the administrative and transfusion points of view. Thus for blood banks in which the turnover of blood is completed in 10 days or less there is no advantage in changing to the Rous‐Turner solution. Further, the use of a small volume standard citrate‐glucose solution leads to the production of plasma with a relatively high protein content, and this is important when blood that is not required for transfusion is to be used for plasma production.

It may be emphasised that of the very many solutions that have been recommended for the preservation of blood, almost all up to now have been selected on the basis of in vitro tests. Such solutions are accordingly only by chance the best for preserving the biological value of stored erythrocytes.

In the selection of new preservative solutions, and particularly in devising new citrate‐glucose mixtures, it is recommended that the effect of the solutions upon the survival of the erythrocytes after transfusion be used as the main criterion of value, in preference to the commonly accepted in vitro tests.

We should like to thank Dr. J. F. Loutit for permission to carry out this work; Dr. M. Maizels for helpful criticisms; Dr. G. L. Taylor of the Galton Laboratories Serum Unit, for very kindly supplying M and N test sera once more, and Dr. L. F. Hewitt for carrying out the pH determination.