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.
Recent in vitro studies have shown that di-2-ethylhexyl-phthalate (DEHP) inhibits the deterioration of RBCs during refrigerated storage in containers that use this compound as a plasticizer. The experiments described in this report were designed to assess whether this in vitro protective effect of DEHP would result in a prolonged in vivo survival of RBCs infused into normal human recipients. Whole blood collected from ten normal donors was stored for 35 days in citrate-phosphate- dextrose-adenine (CPDA-1) anticoagulant contained in polyvinylchloride (PVC) bags plasticized with DEHP or a trimellitate compound that is known to have low leachability. Aliquots of RBCs from each container were then labeled with chromium-51 and were reinfused into the original donors. For blood stored in DEHP-plasticized PVC bags, 24% more red cells survived in vivo 24 hours after reinfusion than was observed when the blood had been stored in trimellitate-plasticized bags (P less than .001). Whole blood stored in glass bottles showed a similar improvement in in vivo survival when DEHP was added in weekly increments to mimic the accumulation of this plasticizer seen during storage in plastic containers. Survival of packed red cells stored in the presence of DEHP increased by 14% compared with storage in trimellitate-plasticized bags (P less than .05). In agreement with previous studies, hemolysis and microvesicle formation were also reduced in the presence of DEHP. These results suggest that proposed new storage systems lacking DEHP should be carefully evaluated to determine whether adequate post-transfusion survival of RBCs may be achieved.
he American blood supply is marginal. The requirements for blood are increasing as the population ages and new and aggressive surgical and oncologic procedures are introduced. These demands require a steadily increasing supply of specialized blood products. Nevertheless, the blood supply has remained static. Every year in the US approximately 12.6 million units of whole blood are collected from approximately 8 million volunteer donors. Approximately 3 percent of the population donate an average of 1.6 times per year. Thirty years ago the donor history questions were brief and screening tests were limited. However, we now have a highly complex and heavily regulated process of qualifying blood donors and screening blood products. The donation process has become very complex, resulting in significant donor loss through deferral and disqualification.The blood supply is now extraordinarily safe, but at a high price in blood availability. Blood shortages are common, with special appeals now routine in summer months and over the winter holidays. These appeals are becoming less effective as the donating public hears repeated blood appeal messages. Also, the appeals seem to energize regular donors instead of attracting new donors. These regular donors may respond to an appeal but are then lost for the ensuing 8 weeks. The net effect is a negligible increase in donations and a "burnout" of regular donors. Donor recruiting specialists are very effective in organizing and conducting blood drives. New approaches, however, for engaging, qualifying, and retaining donors are required.I suggest that we consider the following changes in the way we approach and qualify donors. These suggestions are not new, but the time is right for a comprehensive approach to this issue.
Eighteen patients with sickle-cell disease underwent partial exchange transfusion. Three developed delayed hemolytic reactions, with selective disappearance of transfused cells. All reactions occurred within 6 days of transfusion, and patients presented with the clinical features of painful crises. The two most severe reactions were associated with antibodies to Jka. These patients developed fever, arthritis, and a clinical course suggesting serum sickness. In both patients, other alloantibodies had previously been seen. A fourth patient developed multiple alloantibodies, accelerated destruction of tranfused cells, but milder illness. Such reactions may be commoner than in appreciated and should be suspected when patients have recurrent or severe sickle crises after transfusion. Blood that is nonimmunogenic in antigen systems frequently associated with delayed hemolytic reactions (Rh, Kell, Duffy, and Kidd) is preferred for sickle-cell patients who lack these antigens, especially if these patients have previously demonstrated capability to form erythrocyte alloantibodies.
Tension recording and the patch-clamp technique were used to determine the mechanism underlying vasodilation produced by lemakalim in the rabbit pulmonary artery. Lemakalim produced relaxation of precontracted muscle strips that was inhibited by glibenclamide and tetrapentylammonium ions but not by 2 mM tetraethylammonium (TEA) ions. In single cells dialyzed with 1 mM ATP, lemakalim (10 microM) hyperpolarized cells by approximately 13 mV and activated a time-independent K+ current, averaging only 6.5 pA at -50 mV. Glibenclamide reversed both of these membrane effects of lemakalim but not the lemakalim-induced block of an outward current seen above -20 mV. ATP depletion hyperpolarized cells and selectively unmasked a background K+ current, which was sensitive to glibenclamide but not to TEA, with properties similar to the current activated by lemakalim during membrane hyperpolarization. Furthermore, when intracellular ATP concentrations were varied, a clear correlation was revealed between ATP levels and the magnitude of the depolarization or hyperpolarization seen with either glibenclamide or lemakalim, respectively. These results provide direct evidence that the background current is carried by ATP-sensitive K+ channels rather than by large-conductance Ca(2+)-activated K+ channels and that it underlies the hyperpolarization and relaxation to lemakalim.
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