Hemolytic anemia after ABO nonidentical living donor kidney transplantation

Introduction  ABO compatible non-identical kidney transplants are used frequently. Acquired hemolytic anemia has been reported after ABO mismatched transplantation. Patients of A, B or AB blood groups may receive organs from ABO-compatible, but non-identical donors, mostly from O blood group donors. It may also occur in patients of the AB blood group who receive a kidney from a donor of the A or B blood groups. Patients and methods  ABO non-identical living donor kidney transplantation was done in 214 cases. All studied patients received kidneys from one haplotype HLA mismatched living donors and had pretransplant non-specific blood transfusions. There were 164 males and 50 females with a mean age of 30 years. Ten patients with cyclosporine (CsA)-based therapy developed hemolysis. CsA was stopped in patients maintained on triple immunosuppression (pred, CsA, AZA) and shifted to azathioprine in patients maintained on pred CsA therapy. In all patients pretransplant antibody screen, direct antiglobulin test (DAT) and cytotoxic cross match were all negative. Results  The prognosis was excellent in nine patients, and one died from severe hemolysis. Hemolytic anemia was more frequent among blood group A recipients (60% of our cases) and more severe among recipient blood group B. Six patients received antigen-negative packed RBCs. Univariate analysis demonstrated significant impact for recipient age, donor sex, number of pretransplant blood transfusions, primary immunosuppression, time to onset of diuresis, recipient and donor blood groups. Multivariate analysis restricted the significance to blood group of donor and recipient, time to onset of diuresis and primary immunosuppression. Conclusions  Post transplant hemolysis is infrequent after renal transplantation; however, it may occur with compatible, non-identical ABO blood group donors. Blood group of donor and recipient, time to onset of diuresis and primary immunosuppression (mainly CsA) were significant risk factors in hemolytic anemia in patients after ABO non-identical living donor kidney transplantation. The condition is usually mild and self limited, and change of immunosuppression (stop CsA) can treat the condition.     

ABO血型基因与移植肾急性排斥反应相关性的研究

目的 探讨ABO血型基因与移植肾急性排斥反应(AR)的相关性.方法 采用引物特异性聚合酶链式反应(PCR-SSP)技术检测2009年5月至2010年2月87例肾移植受者及其对应的48例供者ABO(A1、A2、B、O1、O2)血型基因,分析供受者ABO血型基因相合组与错配组受者AR发生、治疗及转归情况.结果 PCR-SSP测定ABO血型基因推定的表型和血清学方法测定ABO血型表型完全相符.供受者ABO血型基因相合组受者50例,发生AR 6例,经甲泼尼龙(MP)冲击治疗后临床逆转.ABO血型基因错配组受者37例,发生AR 11例,经MP冲击治疗后,临床逆转10例,周期性反复发生AR 1例.错配组与相合组受者AR发生率差异有统计学意义(29.7%与12.0%,P<0.05).错配组1例A2O1血型基因受者接受A1O1血型基因供肾后,受者血清检测发现抗A1抗体,抗体效价IgG 1:64,IgM 1:16,移植术后3～10个月周期性反复发生AR,且周期逐渐变短,激素疗效逐渐降低,术后1年SCr达441μmol/L.结论 检测供受者HLA时同步检测ABO血型基因具有很强的可行性.A2血型基因受者适宜选择O型供肾.供受者ABO血型基因错配是介导肾移植术后AR的危险因素,检测供受者ABO血型基因,降低ABO血型基因错配率对预防AR有一定的临床意义.     

The role of the altruistic unbalanced chain in exchange living donor renal transplantation: single-center experience

Background

The exchange donor program in renal transplantation is an efficient solution for recipients with a blood type or crossmatch-incompatible donor. However, this program has some difficulties to define unacceptable human leukocyte antigen matches, deteriorating clinical potential recipient condition, and withdrawal of donor consent. We analyzed the outcomes of exchange donor renal transplantation through the altruistic unbalanced chain.

Methods

Among 152 cases of exchange donor renal transplantation from 1991 to 2010 in our hospital, we performed 58 procedures through altruistic unbalanced chains. We compared their outcomes with the direct and balanced chain group. We analyzed retrospectively whether this program expanded the donor pool, seeking better immunologic, size, and age matching.

Results

The graft survival and acute rejection rates did not differ significantly in the two groups. Of 152 cases, 58 (38.2%) renal transplantations were performed through an unbalanced chain. Seventeen waiting list recipients were transplanted through an altruistic unbalanced chain. In blood type O recipients (n = 32), the causes of registration in the exchange program were ABO incompatibility (93.3%), and positive crossmatch (6.7%). Nine altruistic blood type O donors and 9 (28.1%) type O recipients underwent transplantations through this chain.

Conclusions

We suggest the altruistic unbalanced chain may expand the donor pool with advantages for difficult-to-match pairs. The disadvantages of type O recipients may be overcome through the use of an unbalanced chain. The altruistic unbalanced exchange transplantation program can help easy-to-match subjects, shortening the waiting periods.     

心脏死亡器官捐献供肾ABO血型不相容肾移植八例临床分析

目的探讨心脏死亡器官捐献(DCD)供肾ABO血型不相合肾移植临床疗效和安全性。 方法回顾性分析中国人民解放军联勤保障部队第九二四医院移植科2016年12月至2018年6月实施的8例DCD供肾ABO血型不相容肾移植受者临床资料,其中男性6例,女性2例,年龄26～54岁,群体反应性抗体(PRA)阳性4例,二次肾移植2例,供受者Rh(D)血型均为阴性。根据受者初始血型抗体效价及术前PRA抗体水平制定个体化预处理方案。术后常规监测受者免疫抑制剂血药浓度,重点监测尿量、肾功能、凝血状态和血型抗体水平,PRA阳性受者注意监测供者特异性抗体水平。 结果8例受者经个体化预处理后肾移植手术当天血型抗体IgG效价水平均≤1∶16。术后2周内7例受者血型抗体无反弹。截至2018年6月,8例受者平均随访时间6～18个月。病例1于术后第2周发生体液性排斥反应,采用蛋白A免疫吸附及大剂量丙种球蛋白冲击治疗后恢复。病例2术后2 h出现膀胱出血,持续膀胱冲洗保守治疗后止血,移植肾功能恢复正常。病例3术后第5个月并发严重肺部真菌感染,抗真菌治疗失败后并发呼吸衰竭死亡。病例6术后出现移植肾功能延迟恢复,予血液透析处理后恢复。病例7术后尿量少,术后第4天出现右下肢深静脉血栓(移植肾侧),行下腔静脉滤网植入及溶栓抗凝治疗,效果欠佳,移植肾失功后恢复血液透析治疗。病例8术后第2个月并发药物性糖尿病,目前血糖控制较好。其余2例受者移植肾功能恢复良好。 结论根据受者初始血型抗体效价及PRA水平进行个体化预处理,可安全、有效地实施DCD供肾ABO血型不相容肾移植。     

腹腔器官移植供受者ABO血型基因型及其随机错配率的研究

目的 探讨腹腔器官移植供、受者的ABO血型基因型的分布频率,分析移植供、受者在ABO血清型相同的基础上的基因型随机错配情况.方法 肾移植受者89例、肝移植受者22例为受者组,同期86名无关随机供者为供者组.两组均采用单克隆抗体检测ABO血清学分型,同时采用聚合酶链反应-序列特异性引物(sequence-specific...     

Severe hemolytic anemia due to passenger lymphocytes after living-related bowel transplant

BACKGROUND: Hemolytic anemia following solid organ transplant may be caused by 'passenger' lymphocytes producing antibodies against erythrocytes. This phenomenon has never been described after intestinal transplant. MATERIALS AND METHODS: We report a case of severe, immune-mediated hemolysis due to symptomatic passenger lymphocyte syndrome (PLS) in a 4-yr-old recipient of living donor small bowel transplant. The Coombs'-positive hemolysis was caused by anti-A,B antibodies derived from donor lymphocytes in an ABO-compatible donor-recipient pair (O into A). RESULTS: This complication was successfully and efficiently treated by the novel combined use of group O RBC transfusion, plasmapheresis and rituximab (anti-CD20). CONCLUSIONS: A severe hemolytic anemia due to PLS can occur in bowel transplantation. This complication should be considered when performing ABO-incompatible bowel transplant with a blood group O donor and an A or B recipient. Treatment with plasmapheresis, blood group O transfusion and rituximab has proved successful in our case.     

The “ABO Cross-transplantation Problem” in Liver Transplantation in Korea

ABO blood group matching policy between donor and recipients is a chief element of organ allocation. However, O blood group donors may donate to all other blood group recipients, and ABO cross-transplantation has led to excessively long delays for blood group O. To investigate the consequence of this problem, we analyzed the recipients/donor rates according to ABO blood groups and cross-transplantation rates among them. Data about deceased donors and liver transplants performed in Korea from January 2008 to September 2012 were reviewed. The proportion of recipient to donor in the O blood group was lower compared to non-O groups (0.61). The percentage of O blood group transplantations in the Korean Network for Organ Sharing (KONOS) status 2B was lower than non-O groups (13.6%). In the status 1 and 2A groups, 44.4% of O blood group donors were allocated to non-O transplantations. Also, 30.7% O blood group donors were allocated to non-O transplantations in the status 2B groups. In conclusion, the ABO cross-transplantation in blood group O donors has led to lower transplantation rates of blood group O in status 1, 2A, and especially, the 2B group. Therefore, the KONOS allocation system should be re-evaluated to address this problem.     

Passenger lymphocyte syndrome in renal transplantation: A systematic review of published case reports

BackgroundPassenger lymphocyte syndrome (PLS) is an immune-mediated hemolysis that occurs after ABO-mismatched kidney transplantation. PLS is caused by donor lymphocytes producing antibodies to recipient red blood cells, resulting in hemolysis. The incidence of PLS has been reported to be approximately 20% in patients with ABO-mismatched groups. Nevertheless, there is no comprehensive review of PLS following renal transplantation. In this review, we systematically summarized the data of patients with PLS after renal transplantation to help clinicians diagnose and treat more effectively.MethodsA systematic review was conducted using PubMed, Embase, and Web of Science. All relevant data were collected, including age, sex, and clinical and immune parameters.ResultsA total of 91 published cases were identified. The age ranged from 9 to 70 years old and 58.2% were male. Eighty-six cases were only kidney transplantations, one was liver-kidney transplantation, three were pancreas-kidney transplantations, and one was intestinal-kidney transplantation. Of these cases, 27 received kidneys from deceased donors, whereas 40 received kidneys from living donors. Most patients showed immune hemolysis dominated by anaemia, which was significantly improved after symptomatic support treatment, such as blood transfusion and erythropoietin injection.ConclusionPLS is an immune-mediated disease that can occur in patients with ABO-mismatched renal transplantation, which commonly causes hemolysis, although death or deformities of the graft can also occur in patients with the disorder. Symptomatic supportive treatment is an effective treatment scheme at present, but more effective treatment and prevention schemes still need to be explored.     

The impact of nonidentical ABO cadaveric renal transplantation on waiting times and graft survival

Blood type O recipients of cadaveric renal transplants have longer pretransplant waiting periods than blood type A, B, and AB recipients. To evaluate reasons for and consequences of this discrepancy, we studied both the frequency of various donor and recipient blood type combinations and their outcomes. Among 37,659 cadaveric renal transplants performed during 1983 through 1989, there were 2,625 transplants (7%) received by patients of compatible but nonidentical blood types. Of 18,575 type O donor organs, 16,784 were received by type O patients for a recipient to donor ratio of 0.9. The corresponding ratios were greater than 1.0 for all other blood types (1.02 for blood type A, 1.14 for type B, and 2.18 for type AB). This causes blood type O patients to have a lower access to transplantation and to have significantly longer waiting times than patients of all other blood types. This inequality of access diminished significantly (P less than 0.001) over the years, but did not resolve by 1989. Analysis of relative risk for first graft loss by multiple regression (Cox) showed that transplantation across compatible blood types had a 9.1% higher risk (P less than 0.1) than that of transplantation among identical blood types. Cadaveric renal transplantation within identical blood types optimizes access to transplantation and avoids further aggravating past disadvantages for blood type O recipients.     

Tailored desensitization strategies in ABO blood group antibody incompatible renal transplantation

ABO blood group incompatible renal transplantation, using desensitization procedures, is an effective strategy. Efforts have been made to reduce desensitization: these are usually applied to all patients indiscriminately. The Guy's Hospital ABO blood group incompatible desensitization regimen uses a tiered approach, tailoring strategy according to initial antibody titres. Sixty‐two ABO blood group incompatible living donor transplant recipients were compared with 167 recipients of blood group compatible living donor renal transplants. There were no statistically significant differences in allograft survival rates at 1 or 3 years post‐transplant, rejection in the first year post‐transplant or renal function in the first 3 years post‐transplant. There was a higher rate of death in ABO blood group incompatible transplant recipients – this could be associated with differences in age and HLA mismatch between the two groups. Four ABO blood group incompatible patients experienced antibody‐mediated rejection (no episode was associated with a rise in ABO blood group antibodies). Of the patients who received no desensitization, or rituximab alone, none has experienced antibody mediated rejection or experienced allograft loss. Tailoring the use of desensitization in ABO blood group incompatible renal transplantation according to initial ABO blood group antibody titres led to comparable results to blood group compatible transplantation.     

Maximising living donation with paediatric blood-group-incompatible renal transplantation

Long-term outcomes for paediatric renal transplant recipients have improved over the last 20 years, with better patient and renal allograft survival. As paediatric renal transplantation programmes have increased over this timeframe, living donation has become the favoured modality for renal replacement therapy and is advocated pre-emptively in as many cases as possible. However, one of the main barriers historically to living donation has been ABO blood-group incompatibility, with the result that patients were listed to be on call for a deceased donor renal transplant. The clinical scenario has now changed so that donors and recipients for renal transplantation can be worked up and listed for paired exchange and/or living-related ABO blood-group-incompatible renal transplantation (ABOi). There is extensive data in adult practice, and increasing evidence in paediatric practice that the short- and medium-term outcomes for both patient and renal allograft survival for ABOi is equivalent to that of blood-group-compatible renal transplantation.     

Induction of red blood cell destruction by graft-derived antibodies after minor ABO-mismatched heart and lung transplantation

Heart-lung transplantation (HLT) unlike other solid-organ transplants involves transplantation of a large amount of lymphoid tissue; hence there is considerable potential for graft-versus-host reaction if there is an antigen mismatch between donor and recipient. Due to the shortage of suitable donors, minor ABO-mismatched HLT (group O organs given to A, B, or AB recipients) are performed. Of 84 consecutive HLT at Harefield Hospital, nine fully ABO-matched and nine ABO-mismatched HLT were studied. Six minor ABO-mismatched HLT patients had evidence of immune destruction of recipient's red cells. Haemolysis started from days 4-12 and lasted for a mean of 13 days; in four cases transfusion support was necessary. ABO antibodies incompatible with the recipient ABO antigens, but compatible with the donor, were found in the serum and red cell eluates of these patients. In two cases, these antibodies were detected for over one year after transplantation. These changes were not seen in the fully ABO-matched controls. Our findings suggest that donor-derived lymphocytes from group O organs continue to produce anti-A and/or anti-B after transplantation, and if the recipient is group A, B, or AB, mount a secondary immune response following antigenic stimulation by the recipient's differing ABO antigens. The specific transfusion management of these patients is discussed.     

肝移植术后并发急性溶血性贫血一例

目的报道1例ABO血型不同肝移植术后并发急性溶血性贫血的治疗经验。方法 2010年9月对1例肝癌复发患者行肝癌射频消融联合同种异体背驮式肝移植术,供、受者ABO血型分别为O型及A型。术后第10天发生急性溶血性贫血,血常规示血红蛋白下降至56 g/L,骨髓穿刺检查提示各系增生活跃,粒红比0.52∶1,给予免疫抑制剂及输注O型洗涤红细胞治疗。结果患者一般情况好转,血红蛋白上升,术后第34天上升至111 g/L。随访12个月,患者血红蛋白维持在正常范围。结论对于ABO血型不同但血型相合的肝移植术后并发急性溶血性贫血,免疫抑制剂及输注供体血型的洗涤红细胞可有效缓解溶血,提高肝移植成功率。     

Which ABO‐matching rule should be the decisive factor in the choice between a highly urgent and an elective patient?

ABO blood group matching policy between donor and recipient is a key element of organ allocation. Unequal distribution of the ABO blood groups in the population can lead to inequities in the distribution of organs to potential recipients. Furthermore, High Urgency liver transplant candidates might compromise the chances of transplantation for the elective patients. To compare the influence of the various ABO blood group matching policies on the transplantation rate of HU patients and on the subsequent donor liver availability for elective patients, a simulation study was undertaken. The study shows that in the Eurotransplant liver allocation program, a restricted ABO-compatible matching policy for HU liver patients offers the highest probability of acquiring a liver transplant, for both High Urgency- and elective patients, irrespective of their ABO blood group. A simulation study once again proved to be an elegant tool for objectively analysing various options in a complex organ allocation algorithm.     

Current experience with renal transplantation across the ABO barrier.

Solid organ transplantation has traditionally been governed by the rules of blood group compatibility. Thus, it has been demonstrated that crossing the ABO blood group barrier generally results in hyperacute rejection. However, the A2 subtype of the blood group A is a weaker antigen. Under certain circumstances, organs from donors with blood group A2 can be transplanted across the ABO blood group barrier into recipients of O or B blood type. Since 1986, 33 patients including 24 blood group O and 9 blood group B patients received A2 (30) or A2B (3) donor kidneys. Both cadaver donor (31) and living-related grafts (2) have been undertaken. The mean follow-up since transplantation for the 21 patients with functioning grafts is 36 months, with a 67.2% current graft survival. Immunosuppression for these transplants consisted of azathioprine, prednisone, and cyclosporine, often in combination with prophylactic OKT3 or antilymphocyte globulin as protocol dictated. Special immunosuppressive protocols such as splenectomy or plasmapheresis were not used. The serum of the potential recipient was analyzed for immunoglobulin G (IgG) and immunoglobulin M (IgM) forms of antibody against A1 and A2 red blood cells. There is a strong correlation between a low (less than or equal to 1:8) anti-A1 IgG titer and both early and long-term graft function. Recipients with an IgG titer greater than 1:8 in the pretransplant serum had a much higher incidence of early graft failure. We no longer recommend transplantation of A2 kidneys into O or B recipients with a pretransplant titer of greater than 1:8 but found that recipients with low titers have graft function rates essentially equal to those of ABO-compatible patients. Patients with blood group B have, over time, lower anti-A IgG titers than do blood group O patients. In addition, the graft survival among blood group B patients is 89% compared with 58% among group O recipients. This may be due to the generally low titers found in blood group B recipients. Since instituting a policy in 1988 of not transplanting the kidney when the anti-A IgG titer is greater than 1:8, the survival in O patients is 88%. We recommend the screening of all organ donors with blood group A for the A2 subgroup and believe that transplantation can be safely and successfully performed in certain patients with blood group O or B.(ABSTRACT TRUNCATED AT 400 WORDS)     

Successful three-way kidney paired donation with compatible pairs to increase donor pool

Despite heightened international interest in performing living donor kidney paired donation (KPD) transplantation after the publication of a research protocol by Ross and colleagues in 1997, only a few hundred have been performed worldwide. The major obstacle is that many individuals in end-stage renal disease are of blood type O and can only receive an organ from a donor of blood type O, whereas blood type O donors are “universal donors” and will be able to donate directly with an intended recipient of any blood type unless there is a positive crossmatch. To overcome this, patients with compatible but non-HLA identical donors over 45 years of age should be approached for inclusion in KPD program especially O blood group donors. Inclusion of all these additional pairs into the algorithm greatly increases chances of possible matches for O blood group recipients. We report successful three-way KPD transplantation resulting in transplantation of O blood group patient using compatible O blood group donor from India. None of the patients had delayed graft function or rejection and all had stable graft function on discharge without any medical and surgical complications. We need to allocate O blood group kidneys from compatible donors to overcome the barrier of HLA, non-HLA antibodies and other donor related factors to improve transplant quality and long term outcomes. This will increase transplantation of O blood group patients.     

Factors Affecting Graft Survival After Adult/Child Split-Liver Transplantation: Analysis of the UNOS/OPTN Data Base

When considering advocacy of split-liver transplantation, it is important to understand whether comparable outcomes can be achieved. The goal of this study was to identify donor and transplant characteristics predictive of comparable outcomes by risk factor analysis. Using the United Network for Organ Sharing/ Organ Procurement and Transplantation Network data base between January 1996 and May 2006, first time adult/child split cases (568 adults, 508 children) were examined. In multivariate analysis, recipient medical condition (hospitalization), status 1 assignment, ABO incompatibility, donor age (>40 years), donor body weight (≤40 kg), calculated whole graft volume to recipient body weight ratio (cGRWR ≤1.5%) and no sharing between centers were significant risk factors in adult recipients.
Recipient diagnosis of tumor, dialysis prior to transplant, recipient body weight (≤6 kg), donor age (>30 years), donor history of cardiac arrest after declaration of death and cold ischemia time (CIT > 6 h) increased the risk of graft failure in pediatric recipients. The livers from young donors showed comparable outcomes to whole deceased liver transplantation (LT) when other transplant-related risk factors were minimized in adult recipients. Reducing CIT is important to obtain comparable outcomes to living donor LT in pediatric recipients.     

Equivalent Outcomes for Pediatric Heart Transplantation Recipients: ABO‐Blood Group Incompatible versus ABO‐Compatible

ABO‐blood group incompatible infant heart transplantation has had excellent short‐term outcomes. Uncertainties about long‐term outcomes have been a barrier to the adoption of this strategy worldwide. We report a nonrandomized comparison of clinical outcomes over 10 years of the largest cohort of ABO‐incompatible recipients. ABO‐incompatible (n = 35) and ABO‐compatible (n = 45) infant heart transplantation recipients (≤14 months old, 1996–2006) showed no important differences in pretransplantation characteristics. There was no difference in incidence of and time to moderate acute cellular rejection. Despite either the presence (seven patients) or development (eight patients) of donor‐specific antibodies against blood group antigens, in only two ABO‐incompatible patients were these antibodies implicated in antibody‐mediated rejection (which occurred early posttransplantation, was easily managed and did not recur in follow‐up). Occurrence of graft vasculopathy (11%), malignancy (11%) and freedom from severe renal dysfunction were identical in both groups. Survival was identical (74% at 7 years posttransplantation). ABO‐blood group incompatible heart transplantation has excellent outcomes that are indistinguishable from those of the ABO‐compatible population and there is no clinical justification for withholding this lifesaving strategy from all infants listed for heart transplantation. Further studies into observed differing responses in the development of donor‐specific isohemagglutinins and the implications for graft accommodation are warranted.     

Exchange living-donor kidney transplantation: merits and limitations

BACKGROUND: The shortage of donor organs is one of the major barriers to transplantation worldwide. After the success of the direct exchange donor (swap) program in Korea since 1991, we have developed a swap-around program. However, reports on the long-term outcomes of exchange donor programs are scarce. METHODS: From September 1995 to September 2006, we performed 1193 cases of renal transplantation, including 398 cases from living-unrelated donors. The living-unrelated donors included 129 exchange donors and 269 nonexchange donors. We compared the outcomes of the exchange program with that of the nonexchange program, and examined the merits and limitations of the exchange program. RESULTS: The reasons for the exchange program were ABO incompatibility (n=84, 65.1%), human leukocyte antigen mismatching beyond our criteria (n=39, 30.2%), or positive lymphocyte crossmatch (n=6, 4.7%). The overall 10-year graft survival (86.3%) of exchange transplantation was comparable with that of nonexchange (82.3%) or one- haplotype matched living-related (81.2%) transplantation (P=0.2994). In multivariate analysis, exchange versus nonexchange donors did not affect graft survival. The proportion of blood-type O donors was much lower in the exchange group (29.5%) than in the nonexchange group (42.4%; P=0.026). Blood-type O kidneys were preferentially allocated to blood-type O recipients (78.9%) in the exchange group as compared with the nonexchange group (54.4%; P=0.007). CONCLUSION: We achieved excellent outcomes by using a donor exchange program as an option to reduce the donor organ shortage. However, the exchange donor program has no added benefit for blood-type O recipients.