Random Blood Transfusions Research Articles

The Current Role of Pre-Transplant Blood Transfusions and Tissue Typing in Cadaveric Renal Transplantation

In a retrospective analysis of 74 consecutive cadaveric renal transplants performed at our center during a 38-month period we assessed the influence of random blood transfusions and tissue matching on graft and patient survival. All patients received cyclosporine and low dose prednisone with or without azathioprine as immunosuppressive therapy. Actual patient survival was 100 per cent at 1 year and actuarial 1-year graft survival was 82 per cent. Random blood transfusions and histocompatibility matching at the HLA-DR locus did not influence graft survival. Matching at 2 or more HLA-A and B loci was associated with a significant detrimental influence (p less than 0.05) on graft survival. We conclude that the use of cyclosporine-based immunosuppression overcomes much of the adverse effect of poor tissue matching and may obviate the need for random blood transfusions in cadaveric renal transplantation during the first year of engraftment.

The beneficial effect of pretransplant blood transfusions in cyclosporine-treated cadaver renal allograft recipients.

212 cyclosporine-treated recipients of mismatched first cadaveric renal allografts are evaluated with respect to the effect of pretransplant random blood transfusions. It is determined that transfusions do not effect patient survival or morbidity. Pretransplant random blood transfusions correlate with significantly improved allograft success. There is also a trend, although not statistically significant, for further improvement of allograft survival with increasing numbers of transfusions. The transfusion effect is not related to the time at which the transfusions are given up to 2 years prior to transplantation. Transfused patients have a higher percent reactive antibody (PRA) than untransfused patients, but this does not cause them to wait for a cadaveric allograft significantly longer than the untransfused patients. Rejections are less severe in transfused patients. It is concluded that cyclosporine-treated recipients of first cadaveric renal allografts benefit from pretransplant blood transfusions.

The outcome of 304 primary renal transplants in children (1968-1985).

Of 304 children who received primary renal transplants at the University of Minnesota between January 1, 1968, and December 31, 1985, 48 (16%) were under the age of 24 months, 60 (20%) were 2-5 years old, and 196 (64%) were 6-17 years old at transplantation. Currently, 254 (84%) are alive at 2 months to 18 years following their first transplants, 77% with functioning grafts (188 first, 45 retransplants) and 7% on dialysis. Overall, patient and graft survival were not significantly different from the primary graft outcome of nondiabetic adults. The actuarial primary graft function rates at 1, 5, and 10 years were 100, 100, and 90% in 16 HLA-identical sibling kidneys; 84, 64, and 52% in 210 mismatched related kidneys; and 72, 54, and 47% in 78 cadaver kidneys (p less than 0.002). The 1-year patient survival and primary graft function rates in 44 mismatched related recipients under the age of 24 months were 92 and 88%. The use of deliberate, pretransplant random blood transfusion since 1979 has been associated with a decreased rejection rate. Primary graft function of mismatched related kidneys in children receiving standard immunosuppression has significantly improved from 78% at 1 year in the pretransfusion era to 91% (p less than 0.01) in the transfusion era. The overall primary cadaver graft function rate, however, did not improve in the transfusion era. Whether cyclosporine use will improve the cadaver renal allograft function in very young recipients remains to be established. However, with the use of related donors, even very young children can be transplanted safely and with excellent results.

Improved Allograft Survival in Nonidentical Living Related Donor Transplants using Donor-Specific Blood Transfusions

A total of 78 consecutive HLA nonidentical living related donor transplant recipients with moderate to high stimulating mixed lymphocyte culture indexes underwent a deliberate donor-specific blood transfusion protocol. Of the patients 67 were first and 11 were second allograft recipients.Patients were monitored for immunological responses by cytotoxic B-cold, B-warm and T-warm antibody responses to a random panel of 30 donors, and by serial crossmatches to their donor subset B and T lymphocytes at 5C and 37C before beginning the protocol and after each donor-specific blood transfusion. Patients were followed from 3 months to 2½ years, with allograft survival rates reported by the actuarial method. Survival rates of first allograft recipients were 96.0 plus or minus 2.77, 93.97 plus or minus 3.37, 93.97 plus or minus 3.37 and 90.68 plus or minus 4.50 per cent at 3 and 6 months, and 1 and 2 years, respectively.Of the patients entering the protocol for a primary transplant 20.18 per cent had persistently positive crossmatches. With increasing numbers of previous random blood transfusions a statistically significant sensitization rate was noted. Patient sensitization showed a general pattern of initial development of B-warm lymphocytotoxins resulting in positive B-warm crossmatches, which progressed to T-warm lymphocytotoxins and positive T-warm crossmatches if donor-specific blood transfusions continued. However, on development of B-warm positive crossmatches reversion to a negative crossmatch with successful transplantation was possible upon cessation of transfusions. No patient in the study was rendered nontransplantable due to donor-specific blood transfusions. All 5 patients who were completely disparate suffered amnestic type rejection episodes but following control of the rejection the course mimicked that of mixed lymphocyte culture identical living related donor transplants. Donor-specific blood transfusion is highly successful among first allograft recipients and success in extending the procedure to more disparate relatives is noted.

Planned random donor blood transfusion in preparation for transplantation. Sensitization and graft survival.

Random donor blood transfusions were used to prepare 183 prospective recipients for one-haplotype living-related donor (LRD) grafts or cadaver donor (CD) grafts. Five units of packed red blood cells were administered over a 7-10 day period, and weekly sera were monitored for six weeks. Sensitization was uncommon in men and nulliparous women (8/153), was of low reactivity, and was not a barrier to transplantation. Multiparous women had a 44% frequency of sensitization on presentation and 11/24 initially lacking cytotoxicity developed reactive serum following transfusion. Single-haplotype LRD recipients had 96% one-year graft survival. CD recipients had one-year graft survival of 72%. The rate of transplantation in surviving candidates exceeded 90%, and supports the hypothesis of a protective immune response.

PREDICTIVE FACTORS AFFECTING FIRST PEDIATRIC CADAVERIC TRANSPLANT SURVIVAL

Transplantation remains the optimal replacement therapy for children with end stage renal disease. Cadaveric allograft survival (surv)has improved over the past decade. We reviewed our experience with 61 first cadaveric transplants performed from 1972 through 1982. Twenty-three recipients(38%)were female and 38(62%) were male;the mean age was 11.2 yrs.(range 2-19). Forty-two (69%) were white,18(29%)black,and 1(2%)hispanic. Thirty-five(57%)had received at least 5 random donor blood transfusions(trans). Thirty (50%)were matched for a minimum of 2 HLA A and B antigens (Ag). Proportional hazards analysis(Cox's model)was used to examine 5 explanatory variables:sex,age,race, ≥5 trans,and number(no.)of Ag matches. Sex,age,and race did not affect graft surv. In this population,trans alone did not improve transplant surv(p>0.2).The no. of Ag matches was positively correlated with graft surv.(B=-0.3, p<0.02).The combination of trans and Ag matching provided excellent allograft surv(94% at 1 yr.67% 5 yrs).This prompted an examination of the data including a variable termed AgTrans, a first-order interaction of no. of Ag matches and trans status. AgTrans was the strongest factor associated with prolonged surv.(B=-0.47, p<0.001).Use of the model predicts that at the time at which graft surv.would be 50% with <5 trans and no Ag matches, it would increase to 68% with a 2 Ag match,and increase further to 85% with both a 2 Ag match and ≥5 trans.In summary,Ag matching acts as an initiator in pediatric cadaveric transplantation and ≥5 trans act as a promotor of graft function.

New approaches to donor crossmatching and successful transplantation of highly sensitized patients.

A class I HLA molecule may bear not only a private or unique determinant, but a shared, yet discrete, public epitope. These public determinants occur with a much higher frequency in the random donor population than the associated private determinants--and thus, are encountered more often in random donor blood transfusions and in renal transplantation. Sera from highly sensitized dialysis patients have been reported to contain a restricted number of antibodies to public determinants rather than a diverse array of antibodies directed against the private HLA-AB epitopes. As detailed in this report, comprehensive serum analysis of the public antibodies in highly sensitized transplant candidates has optimized identification of potential crossmatch-compatible donors and has avoided needless crossmatches. During the past two years, the incidence of renal transplantation from cadaveric donors to highly sensitized recipients has doubled at this institution. At 10-25 months following transplantation, 70% of these allografts are functioning. Private HLA class I antigen incompatibility was not a barometer for exclusion in the final donor crossmatch of these highly sensitized recipients. Furthermore, positive donor T cell crossmatches with sera obtained more than six months prior to transplantation may not represent an impediment to successful transplantation. We conclude that the approach of detailed antibody analysis can result in an improved outlook for successful transplantation of more dialysis patients who are highly sensitized to the class I HLA alloantigens.

Transfusion therapy for renal transplant candidates

Improved graft survival was observed in cadaver-kidney recipients prepared with random donor blood transfusions and in selected living-related-kidney recipients primed with transfusions from the kidney donor. This seems to justify a purposeful transfusion policy in these patients.

Influence of pre- and perioperative blood transfusions on renal allograft survival.

One hundred and seventy-nine patients who received transplants between January 1975 and May 1980 have been studied retrospectively in order to elucidate the effect of pre- and perioperative random third-party blood transfusions on first cadaveric renal allograft survival. The 179 patients were approximately evenly divided into four groups; those who received blood transfusions preoperatively only (group 1, n = 45), received blood both pre- and perioperatively (group 2, n = 48), received blood perioperatively only (group 3, n = 37), or were never transfused before transplantation or perioperatively (group 4, n = 49). Actuarial graft survival for group 1 was 73% at 1 to 4 years, which was significantly better (P less than or equal to 0.02) than each of the other three groups at all four intervals. Groups 2, 3, and 4 were statistically identical to each other and had graft survivals of 52% or less at 1 to 4 years. From our study we conclude that: (1) Preoperative transfusions confer significant benefit on recipients of first cadaveric renal allografts. (2) Perioperative blood transfusions are without significant benefit in previously untransfused patients, and significantly lower allograft survival in previously transfused patients. A rational blood transfusion policy based on these results would be to transfuse renal allograft recipients preoperatively and avoid perioperative blood transfusions as much as possible.

Effect of Deliberate Blood Transfusions in Cadaveric Kidney Allografts at a Single Center

The effectiveness of deliberate pre-transplant blood transfusions was compared in randomly transfused and nontransfused patients who acted as controls at a single transplant center. The patients in the pre-transplant transfusion group who had never been transfused had better graft survival than all other groups. Next, were those patients who had previous random transfusions and were then placed in the deliberately transfused group. Those who had received random blood transfusions but were not in the protocol and those patients who never had transfusions did the poorest.Those patients never transfused previously who received the scheduled transfusions had far lower levels of antibodies than those who had had previous transfusions and those with previous transfusions who were then entered into the prospective transfusion protocol. The patients who had B cold cytotoxic antibodies had the highest graft survival rates. Timing was important, with the group receiving the last transfusions 3 to 6 weeks before transplantation doing significantly better than any other group. Histocompatibility locus-A and B antigen distribution among the groups did not bias the data.

Aplastic Anemia Treated by Allogeneic Bone Marrow Transplantation: A Report on 49 New Cases from Seattle

AbstractForty-nine patients with severe aplastic anemia, 33 due to unknown cause, 11 drug or chemical related, 2 associated with hepatitis, 1 with paroxysmal nocturnal hemoglobinuria, and 2 possibly associated with Fanconi syndrome did not show recovery after 0.5–96 (median 2) mo of conventional therapy. Twenty-two were infected and 21 were refractory to random platelet transfusions at the time of admission. All were given marrow grafts from HLA-identical siblings. Forty-five were conditioned for grafting by cyclophosphamide (CY), 50 mg/kg on each of 4 successive days, and four by 1000 rad total body irradiation. All were given intermittent methotrexate therapy within the first 100 days of grafting to modify graft-versus-host disease (GVHD). Three patients died from infection too early to evaluate (days 1–8). Forty-six had marrow engraftment. Of these, 20 are surviving with good peripheral blood counts between 186 and 999 days, and 18 have returned to normal activities. Chronic GVHD is a problem in five. Twelve patients died of infection following rejection of the marrow graft. Twelve patients died with bacterial or fungal infections or interstitial pneumonia and active GVHD or soon following resolution of GVHD. Two patients died with marrow engraftment and no GVHD, one with an interstitial, and the other with a bacterial pneumonia. Thirty-six patients who had received random donor blood transfusions were randomly assigned to receive either CY or procarbazine-antithymocyte globulin-CY as conditioning regimens to test whether the incidence of graft rejection could be decreased. There was no difference in the incidence of graft rejection between the two regimens. In 13 patients with rejection, second transplants were attempted either with the original marrow donor (9 patients) or another HLA-identical sibling (4 patients). Three of these transplants were not evaluable, seven were unsuccessful and three were successful with only one of the three surviving for more than 468 days. In conclusion, the long-term survivial of 41% of the patients in the present study is similar to that achieved in our first 24 patients, and confirms the importance of marrow transplantation for the treatment of severe aplastic anemia. Marrow graft rejection, GVHD, and infections continue to be the major causes of failure.

Aplastic anemia treated by allogeneic bone marrow transplantation: a report on 49 new cases from Seattle

Forty-nine patients with severe aplastic anemia, 33 due to unknown cause, 11 drug or chemical related, 2 associated with hepatitis, 1 with paroxysmal nocturnal hemoglobinuria, and 2 possibly associated with Fanconi syndrome did not show recovery after 0.5–96 (median 2) mo of conventional therapy. Twenty-two were infected and 21 were refractory to random platelet transfusions at the time of admission. All were given marrow grafts from HLA-identical siblings. Forty-five were conditioned for grafting by cyclophosphamide (CY), 50 mg/kg on each of 4 successive days, and four by 1000 rad total body irradiation. All were given intermittent methotrexate therapy within the first 100 days of grafting to modify graft-versus-host disease (GVHD). Three patients died from infection too early to evaluate (days 1–8). Forty-six had marrow engraftment. Of these, 20 are surviving with good peripheral blood counts between 186 and 999 days, and 18 have returned to normal activities. Chronic GCHD is a problem in five. Twelve patients died of infection following rejection of the marrow graft. Twelve patients died with bacterial or fungal infections or interstitial pneumonia and active GVHD or soon following resolution of GVHD. Two patients died with marrow engraftment and no GVHD, one with an interstitial, and the other with a bacterial pneumonia. Thirty-six patients who had received random donor blood transfusions were randomly assigned to receive either CY or procarbazine-antithymocyte globulin-CY as conditioning regimens to test whether the incidence of graft rejection could be decreased. There was no difference in the incidence of graft rejection between the two regimens. In 13 patients with rejection, second transplants were attempted either with the original marrow donor (9 patients) or another HLA-identical sibling (4 patients). Three of these transplants were not evaluable, seven were unsuccessful and three were successful with only one of the three surviving for more than 468 days. In conclusion, the long-term survival of 41% of the patients in the present study is similar to that achieved in our first 24 patients, and confirms the importance of marrow transplantation for the treatment of severe aplastic anemia. Marrow graft rejection, GVHD, and infections continue to be the major causes of failure.

Probability-theoretic investigations on Inheritance, VI. Rate of danger in random blood transfusion

Probability-theoretic investigations on Inheritance, VI. Rate of danger in random blood transfusion