Posttransfusion Survival Of Red Cells Research Articles

Measurement of posttransfusion red cell survival with the biotin label.

The goal of this review is to summarize and critically assess information concerning the biotin method to label red blood cells (RBC) for use in studies of RBC and transfusion biology-information that will prove useful to a broad audience of clinicians and scientists. A review of RBC biology, with emphasis on RBC senescence and in vivo survival, is included, followed by an analysis of the advantages and disadvantages of biotin-labeled RBC (BioRBC) for measuring circulating RBC volume, posttransfusion RBC recovery, RBC life span, and RBC age-dependent properties. The advantages of BioRBC over (51)Cr RBC labeling, the current reference method, are discussed. Because the biotin method is straightforward and robust, including the ability to follow the entire life spans of multiple RBC populations concurrently in the same subject, BioRBC offers distinct advantages for studying RBC biology and physiology, particularly RBC survival. The method for biotin labeling, validation of the method, and application of BioRBCs to studies of sickle cell disease, diabetes, and anemia of prematurity are reviewed. Studies documenting the safe use of BioRBC are reviewed; unanswered questions requiring future studies, remaining concerns, and regulatory barriers to broader application of BioRBC including adoption as a new reference method are also presented.

Investigating Direct Non-Age Metrics of Stored Blood Quality Loss

Long storage times for blood products are often unavoidable. Product age is essentially the only indicator used today for Red Blood Cell (RBC) quality loss during storage. Much controversy persists over the impact of RBC age on transfusion outcomes, as studies on this remain inconclusive. Such inconsistency may arise from unit-to-unit variability, which likely introduces some age-independence to RBC state. Thus, quality metrics other than storage time could aid with inventory management and/or treatment decisions. RBC membrane mechanical fragility is proposed here as one such candidate in vitro metric: it aggregately reflects a range of biochemical and biomechanical changes associated with storage lesion, and can provide a more comprehensive characterization of particular units than other properties. Preliminary data suggest this property can vary substantially among units of equal age, and further work now in progress is investigating its correlation to post-transfusion red cell survival in vivo.

The effect of prestorage irradiation on posttransfusion red cell survival.

Transfusion-associated graft-versus-host disease (TA-GVHD) may occur whenever immunologically competent allogeneic lymphocytes are transfused to an immunocompromised recipient. Irradiation of blood components eliminates the risk of TA-GVHD but may damage the cellular elements in the transfused component, particularly if the cells are stored for prolonged periods in the irradiated state. To study the effect of irradiation on long-term storage of red cells, AS-1 red cells from eight normal subjects were prepared on two occasions. On one occasion, the units were stored as standard AS-1 red cells for 42 days at 4 degrees C; on the other, they were exposed to 3000 cGy radiation within 4 hours of collection and then were stored as AS-1 red cells for 42 days at 4 degrees C. The donations were at least 12 weeks apart. Irradiated units demonstrated significant elevations in poststorage plasma hemoglobin (Hb) (623 +/- 206 vs. 429 +/- 194 g/dL [6230 +/- 2060 vs. 4290 +/- 1940 g/L], p less than 0.02) and plasma potassium (78 +/- 4 vs. 43 +/- 9 mEq/L [78 +/- 4 vs. 43 +/- 9 mmol/L], p less than 0.01) and significant decreases in red cell ATP (1.9 +/- 0.2 vs. 2.1 +/- 0.3 microM/g Hb, p less than 0.04) and 24-hour posttransfusion red cell recovery (68.5 vs. 78.4%, p less than 0.02), as compared to nonirradiated units. It can be concluded that irradiation with 3000 cGy damages red cells and that long-term storage in the irradiated state may enhance this damage. Red cells should not be stored for 42 days after irradiation with 3000 cGy.

Posttransfusion survival of red cells frozen for 8 weeks after 42-day liquid storage in AS-3.

Current standards recommend that red cells (RBCs) should be frozen within 6 days of donation. There are situations, however, in which it is desirable to freeze RBCs that are older than 6 days, such as for the salvage of rare or autologous units. To determine the therapeutic efficacy of RBCs frozen after prolonged liquid storage, standard units were drawn from nine normal donors and stored at 4 degrees C for 42 days in a nutrient-additive solution, AS-3. 51CrRBC survival assays were performed (24-hour survival: 78.2 +/- 12.4%; n = 8) and the units were frozen at -80 degrees C in glycerol for 8 weeks. After deglycerolization, the mean RBC recovery was 81.0 +/- 4.1 percent and the mean 24-hour 51Cr survival was 78.0 +/- 9.1 percent. The index of therapeutic effectiveness (ITE) was determined by multiplying the postdeglycerolization 24-hour 51Cr survival by the mean RBC recovery (63.3 +/- 9.2). ITE values greater than 60 percent (75% 51Cr survival x 80% RBC recovery) were considered acceptable. Mean adenosine triphosphate levels declined from an initial 3.81 +/- 0.56 micromol per g of hemoglobin to 2.33 +/- 0.55 micromol per g after frozen storage. These findings show that an acceptable percentage of RBCs survives frozen storage after maximum liquid storage (mean ITE greater than 60%). If necessary, RBCs stored in AS-3 can be frozen at any time before 42 days.

II. Relation between Cellular Morphology and Viability

Red cells collected in CPD, suspended in SAGM solution and stored for 42 days at +4 degrees C, were tested before and after incubation for 1 h at 37 degrees C with respect to autologous 24-hour posttransfusion red cell survival, morphology, fluidity at low shear rate and adenylate content. Warming and to some extent chromium labelling of the cells resulted in improvement of the morphology and fluidity but in no increase in adenosine triphosphate, total adenylate concentration or posttransfusion survival. The conclusion is drawn that short-term improvement of the morphology before transfusion does not result in increased viability.

Studies on the mechanism of human red cell loss of viability during storage at +4 degrees C in vitro. I. Cell shape and total adenylate concentration as determinant factors for posttransfusion survival.

Red cells stored in SAGM medium for 42 days at +4 degrees C were rejuvenated by bicarbonate, pyruvate and adenosine. Autologous 24-hour posttransfusion survival was determined in untreated as well as rejuvenated cells and showed an improvement from 77.4 +/- 4.7 to 89.2 +/- 7.2%. The erythrocyte adenylate energy charge decreased relatively more than the total adenylate concentration during storage, but the latter correlated better with posttransfusion red cell survival. Considerable deteriorations in red cell morphology (expressed as morphology index) and in deformability (measured as red cell fluidity) were observed during storage but were partly reversed by rejuvenation. The morphology index and the posttransfusion survival showed a significant correlation (r = 0.95, p less than 0.005) after, but not before, rejuvenation, indicating that the remaining changes are more permanent and decisive of survival. It is suggested that, in the proportion of stored erythrocytes which respond to rejuvenation, the capacity and time dependence of recovery of normal shape and flexibility are important.

Antioxidant metabolism during blood storage and its relationship to posttransfusion red cell survival.

The status of the erythrocyte antioxidant defense system and its relationship to posttransfusion red cell survival were determined in erythrocytes stored for 35 or 42 days in CPD-A1 anticoagulant with a saline-adenine-glucose additive. As storage progressed, there was a significant increase in incubated Heinz body formation (P less than .001) and a significant decrease in reduced glutathione (GSH) stability (P less than .001). Stimulated pentose phosphate shunt activity also declined during storage (P less than .06), while unstimulated shunt activity remained unchanged. The increase in Heinz body formation was associated with decreased GSH stability (r = -.77, P less than .001), which in turn was associated with the decline in stimulated pentose shunt activity (r = .67, P less than .001). The changes in Heinz body formation (r = -.85), GSH stability (r = .83), and stimulated pentose shunt activity (r = .54) were all significantly (P less than .001) related to the decline in adenosine triphosphate (ATP) content of the erythrocyte. Red cell survival 24 hours after transfusion was significantly related to the GSH stability (r = .80, P less than .001) and to the ATP concentration (r = .76, P less than .005) on the day of transfusion. Thus, dysfunction of the erythrocyte antioxidant defense system occurs during blood storage and appears to be related, in part, to ATP depletion. The ability to maintain a normal reduced glutathione concentration during oxidant stress appears to be an important determinant of red cell survival in the peritransfusion period.

Viability of red cells stored in diminished concentration of citrate.

A comparison was made between the post-transfusion survival of red cells stored in standard ACD-A and in modified ACD-A, containing two-thirds the amount of citrate. Measurements of survival after 28 d storage in both solutions were made in each of six subjects. Mean post-transfusion survival with the two solutions was almost identical. When the results in one subject in whom survival was particularly bad with both solutions were omitted mean values at 24 h were 74.0% for standard ACD-A and 74.9% for modified ACD-A. It is concluded that viability is just as well maintained in modified ACD-A as in standard ACD-A. The results also provide further evidence of large differences between donors with respect to the maintenance of red cell viability during storage.

Transfusion of long stored whole blood or washed red blood cells incubated with adenine and inosine.

Full unit autotransfusions of long stored ACD blood, incubated with adenine and inosine at 37 C., were given to healthy young male volunteers. Red cells of blood stored for 35 days showed, after regeneration, a significant increase in ATP and a 24‐hour posttransfusion survival of 78.8 per cent (70.9–85.9%); red cells of blood stored for 42 days, thus regenerated, showed a similar increase in ATP and a 24‐hour posttransfusion survival of 75.6 per cent (71.5–80.6%). These results were not significantly different from those obtained with 10‐ml token autotransfusions of blood similarly treated, the posttransfusion survival of red cells in token transfusions being 78.8 per cent for blood stored 35 days prior to regeneration with adenineinosine and 74 per cent for blood stored for 42 days prior to regeneration. Available data on toxicity of adenine and inosine have been critically reviewed: Chance of direct toxic effects with the small amounts involved may be dismissed when few transfusions are involved; however, uric acid overload must be considered when multiple transfusions are required within a short period of time. A single washing with saline‐glucose solution reduces by 90 per cent the concentration of un‐metabolized adenine and inosine, and of the product of their metabolism, hypoxanthine. The washing procedure involves a loss of only 0.55 per cent of the total red blood cell population; washing additionally reduces the amount of free hemoglobin. Washing has no effect on the ATP or red blood cell viability, and is recommended when multiple transfusions of cells treated with adenine and inosine are required in a short period of time.

Effect of addition of adenine and inosine on ATP and posttransfusion survival of red cells of stored blood: Strumia, M. M., and P. V. Strumia. Transfusion, 7: 381–382, 1967

Effect of addition of adenine and inosine on ATP and posttransfusion survival of red cells of stored blood: Strumia, M. M., and P. V. Strumia. Transfusion, 7: 381–382, 1967

Effect of lactose, dextran and albumin on recovery and survival of frozen red cells.

We have studied the effect of albumin and dextran, with and without previous modification with lactose, on the recovery and posttransfusion survival of red cells subjected to rapid freezing and thawing.Dextran and albumin have been found to protect red cells during freezing and thawing, with a recovery rate of 98.5 and 98.57%, respectively. A mean survival of 69.14% of red cells was obtained 24 hours posttransfusion when the red cells were treated with lactose, prior to freezing with dextran.A relationship has been found to exist between the mean corpuscular volume of the frozen red cells and the posttransfusion survival; potassium loss, stability, dimensional changes and O2 dissociation of frozen red cells were determined.

In vitro recovery and posttransfusion survival of red cells modified with sugars, frozen, stored in the frozen state and rapidly thawed.

In vitro recovery and posttransfusion survival of red cells modified with sugars, frozen, stored in the frozen state and rapidly thawed.