ABO Blood Group Incompatibility Research Articles

Experts' considerations on HLA-haploidentical stem cell transplantation.

Recently, novel strategies to control graft-versus-host disease and facilitate engraftment have allowed an increasing number of human leukocyte antigen (HLA)-haploidentical hematopoietic stem cell transplantation (haploHSCT) to be performed. A meeting was convened to review the biological rationale and the clinical results of various T-cell-depleted (TCD) and T-cell-replete (TCR) HLA-haploidentical 'transplant platforms'. The objective of the meeting was to promote discussion and consent among leading researchers in the field on three main crucial issues for haploHSCT: (i) eligibility criteria, (ii) choice of the most suitable donor, and (iii) choice of the most appropriate transplant platform. The experts in attendance agreed that a patient who is eligible for an allogeneic transplant and lacks an HLA-identical sibling or an HLA-matched unrelated donor should be considered for an alternative donor transplant. Together with the experience of the individual center, the most important decision criteria in choosing an alternative donor source should be the rapidity of transplantation so as to avoid disease relapse/progression. The choice of the mismatched donor should be driven by younger age, ABO blood group compatibility, and Cytomegalovirus status. If a TCD transplant is planned, NK-alloreactive donors and/or the mother should be preferred. Prospective comparative studies are needed to establish the relative efficacy of different transplant platforms. However, expertise in stem cell manipulation and in adoptive immunotherapy is essential if a TCD transplant platform is chosen.

Optimization of blood supply chain with shortened shelf lives and ABO compatibility

In clinical practice, red blood cells (RBCs) have a maximal shelf life (MSL) of 42 days. Recent studies suggest managing RBC inventory with a more restrictive MSL. To this end, a new simulation optimization (SO) framework is proposed for blood supply chain inventory management with ABO blood group compatibility. The inventory objective is to minimize the expected system outdate rate under a predetermined maximally allowable shortage level. The proposed SO framework is incorporated with a new metaheuristic optimization algorithm, TA–TS, to identify near-optimal inventory policies in reasonably acceptable computational time. The new SO framework is shown to offer a better tradeoff between solution accuracy and computational expense. The efficiency of the proposed framework is evaluated in detail for a single-hospital single-blood center supply chain system, in which the MSL of RBC units are shortened to 7, 14 and 21 days. A recently-developed replenishment policy based on old inventory ratio (the OIR policy developed by Duan and Liao (2013b)) is used to control the freshness of the entire inventory. Three different scenarios are investigated: (1) no ABO compatible substitution; (2) ABO compatible substitution at hospital only; (3) ABO compatible substitution at both hospital and blood center. Using the proposed SO framework, we are able to identify a near-optimal solution for each of these scenarios and quantify the potential savings offered by ABO compatible substitution. In the ABO compatible substitution scenarios, there is a clear trend of the increased use of group O blood. As the MSL decreases, group O blood are needed more frequently to substitute for other ABO/Rh(D) compatible blood types. Allowing ABO/Rh(D)-compatible blood substitution helps reduce the system-wide outdate at least by 16% even under the most restrictive MSL. For more relax MSL of 14 days and 21 days, the proposed framework is capable of keeping the highest system-wide outdate rate at as little as 2%.

A study of neonatal hyperbilirubinemia in a tertiary care hospital

Background: Neonatal Hyperbilirubinemia is a common problem encountered in neonates and often requires admission and treatment. Aims & Objectives: To determine the incidence, etiology and risk factors associated with neonatal hyperbilirubinemia in a tertiary care hospital. Materials and Methods: A retrospective study was conducted on data obtained on live births for 2012 and 2013.All treated cases of neonatal hyperbilirubinemia were analyzed and data on gender, gestation age, mode of delivery, blood group incompatibility, sepsis, parity and birth weight were obtained. Results: 753 neonates were treated for hyperbilirubinemia, the total number of live births was 5589. The incidence of neonatal hyperbilirubinemia was 13.47%. ABO blood group incompatibility was the most common cause of hyperbilirubinemia. Conclusion: Blood Group incompatibilities, sepsis, and cephalohematoma were the common causes of hyperbilirubinemia, however in nearly a third of all cases etiology could not be determined. Preterm gestation and low birth weight were associated risk factors.

Imaging Diagnosis of Neonatal Anemia: Report of Two Unusual Etiologies

Anemia in neonatal period is rare, with the common causes being Rh and ABO blood group incompatibility, hemorrhagic disease of newborn, congenital hemolytic anemia, hemoglobinopathies, and TORCH (toxoplasmosis, rubella, cytomegalovirus, herpes virus) infections. Congenital leukemia and infantile osteopetrosis (OP) are among the rare causes of neonatal anemia. A review of the literature shows approximately 200 reported cases of congenital leukemia. Articles describing the imaging features of congenital leukemia are still rarer. Infantile OP, another rare disorder with a reported incidence of 1 in 250,000 has characteristic imaging features, which are diagnostic of the disease. We report a case each, of two rare diseases: Congenital leukemia and infantile osteopetrosis. Additionally, our report highlights the radiological and imaging features of congenital leukemia and infantile OP and their crucial role in arriving at an early diagnosis.

Effect of ABO Blood Group Incompatibility on the Outcome of Single-Unit Cord Blood Transplantation after Myeloablative Conditioning

ABO blood group incompatibility between donor and recipient has been associated with poor transplant outcomes in allogeneic hematopoietic stem cell transplantation. However, its effect on the outcome of cord blood transplantation (CBT) has yet to be clarified. We retrospectively analyzed 191 adult patients who received single-unit CBT after myeloablative conditioning for malignant disease in our institute. Major mismatch showed a significantly lower incidence of platelet engraftment compared with ABO match as a reference (hazard ratio, .57; P = .01). Nevertheless, there was no increase in graft-versus-host disease, transplant-related mortality, and overall mortality after ABO-incompatible CBT. These data suggested that donor–recipient ABO incompatibility does not have a significant impact on outcome after myeloablative CBT for hematological malignancies.

Analysis of Donor and Recipient ABO Incompatibility and Antibody-Associated Complications after Allogeneic Stem Cell Transplantation with Reduced-Intensity Conditioning

Allogeneic hematopoietic stem cell transplantation (HSCT) can be performed across the ABO blood group barrier. The impact of ABO incompatibility on clinical outcome is controversial. A retrospective analysis of 310 patients who underwent HSCT with reduced-intensity conditioning between 1998 and 2011 was performed to investigate the frequency and clinical implications of anti-RBC antibodies in passenger lymphocyte syndrome (PLS) after minor ABO mismatch (mm), persistent or recurring recipient type ABO antibodies (PRABO) after major ABO mm HSCT, and autoimmune hemolytic anemia (AIHA). Transplantation characteristics and clinical outcome were analyzed by univariate and multivariate analysis for groups with or without anti-RBC antibodies. ABO blood group incompatibility did not affect clinical outcome despite an increased requirement of blood transfusion. Twelve patients with AIHA, 6 patients with PLS, and 12 patients with PRABO post-HSCT were identified. AIHA did not affect overall survival (OS) or transplant-related mortality (TRM), but patients with AIHA had a lower incidence of grades II to IV acute graft-versus-host disease (P = .05). OS in the PLS group was 0% compared with 61% in the whole group receiving minor ABO mm transplants (P < .001). Comparing PRABO patients with those receiving a major ABO mm HSCT, the OS was 17% versus 73% (P = .002) and TRM was 50% versus 21% (P = .03). At our center, PLS after minor ABO mm and PRABO antibodies after major ABO mm HSCT are significant risk factors for decreased OS and TRM. Our results suggest that occurrence of unexpected ABO antibodies after HSCT warrant a wider investigation individual to find the underlying cause.

CD144+ endothelial microparticles as a marker of endothelial injury in neonatal ABO blood group incompatibility.

ABO antigens are expressed on the surfaces of red blood cells and the vascular endothelium. We studied circulating endothelial microparticles (EMP) in ABO haemolytic disease of the newborn (ABO HDN) as a marker of endothelial activation to test a hypothesis of possible endothelial injury in neonates with ABO HDN, and its relation with the occurrence and severity of haemolysis. Forty-five neonates with ABO HDN were compared with 20 neonates with Rhesus incompatibility (Rh HDN; haemolytic controls) and 20 healthy neonates with matched mother and infant blood groups (healthy controls). Laboratory investigations were done for markers of haemolysis and von Willebrand factor antigen (vWF Ag). EMP (CD144(+)) levels were measured before and after therapy (exchange transfusion and/or phototherapy). vWF Ag and pre-therapy EMP levels were higher in infants with ABO HDN or Rh HDN than in healthy controls, and were significantly higher in babies with ABO HDN than in those with Rh HDN (p<0.05). In ABO HDN, pre-therapy EMP levels were higher in patients with severe hyperbilirubinaemia than in those with mild and moderate disease or those with Rh HDN (p<0.001). Post-therapy EMP levels were lower than pre-therapy levels in both the ABO HDN and Rh HDN groups; however, the decline in EMP levels was particularly evident after exchange transfusion in ABO neonates with severe hyperbilirubinaemia (p<0.001). Multiple regression analysis revealed that the concentrations of haemoglobin, lactate dehydrogenase and indirect bilirubin were independently correlated with pre-therapy EMP levels in ABO HDN. Elevated EMP levels in ABO HDN may reflect an IgG-mediated endothelial injury parallel to the IgG-mediated erythrocyte destruction and could serve as a surrogate marker of vascular dysfunction and disease severity in neonates with this condition.

ABO Blood Group Incompatibility among the Bengali Muslims of Cachar District, Assam

Present study is an attempt to investigate the fertility performance with reference to ABO incompatibility among 89 Bengali Muslim fertile couples of Cachar District, Assam. The findings of the present study reveal that mean conception and mean live birth are more among the compatible couples but mean pregnancy wastage, particularly miscarriage, is high among the incompatible couples.

Blood transfusion; additional historical aspects. Part 1. The birth of transfusion immunology

The decades around the turn of the 19th into the 20th centuries covered a seminal period in the history of transfusion medicine as there was an increasing appreciation of a potential role in the management of surgical and obstetric bleeding, and also in severe non-surgical anaemias. The main obstacles to transfusing human blood were first the occasional devastating adverse reactions due, we now know, to ABO blood group incompatibility; and second the awkward propensity of shed blood to clot. This article describes in more detail how the pioneers in human transfusion immunology in the late 19th century and early 20th century learnt to recognise and avoid ABO incompatibility, and includes some hitherto obscure and rarely cited material. A companion article (Boulton, 2013, Submitted for publication) describes early attempts to find suitable anticoagulants.

Bronchiolitis obliterans after allogeneic hematopoietic SCT: further insight—new perspectives?

Bronchiolitis obliterans (BO) is a late non-infectious pulmonary complication after allogeneic hematopoietic SCT. Among 982 patients after myeloablative hematopoietic SCT between January 2000 and October 2010, 68 were diagnosed with BO according to NIH criteria. The median onset of BO was 18 months post transplant, 5-year cumulative incidence was 5.8% and 5-year mortality 41%. BO prevalence rate was 10% among all long-term surviving hematopoietic SCT recipients and 12% among chronic GVHD-patients. Chronic GVHD, peripheral SCT and ABO blood group incompatibility were identified as risk factors associated with BO. IgG levels were significantly decreased at the onset of BO (6.7 g/L±0.7, P=0.001), the mean exhaled NO concentrations were lower in BO-patients than in stem cell recipients without BO (14 p.p.b.±0.9 vs 20 p.p.b.±2.1) or healthy controls (25 p.p.b.±2.4, P<0.001). Hypoxia-inducible factor 1 alpha (HIF-1α) was significantly elevated in BO as compared with healthy controls or GVHD-patients without lung involvement (340±61 vs 127±22 vs 140±32, P=0.02). Calculated 5-year survival was superior in female than in male BO-patients (86 vs 45%, P=0.04). These results emphasize the relevance of BO as serious late complication with substantial mortality and point to essential pathophysiological changes due to regulatory responses to hypoxia.

Therapeutic apheresis in kidney transplantation: A review of renal transplant immunobiology and current interventions with apheresis medicine

Transplantation is the treatment of choice for end stage renal disease. Kidney transplants convey both a significant survival advantage to the individual recipient as well as cost savings to the medical system. Circulating alloantibodies directed against donor human leukocyte antigens and blood group antigens are fairly common among potential recipients. They are known to injure allografts, shorten allograft survival, and limit access to kidney transplantation. Hence, screening for pretransplant alloantibodies using complement dependent cytotoxic cross-matching and more sensitive techniques such as the solid phase assays, have become routine in an attempt to avoid incompatible donor-recipient pairs and risk stratify those with donor specific antibodies (DSA). By removing harmful antibodies, therapeutic apheresis (TA) has become a critical tool for improving access to transplantation in cases where the immunologic risk had previously been considered unacceptable. It has also allowed us to transplant across the barrier of ABO blood group incompatibility and expand the pool of donors with reasonable success. Furthermore, it is an important tool in the treatment of antibody-mediated rejection. Advanced apheresis technologies, such as immunoadsorption, and the use of TA in combination with innovative paired-donor exchange programs, offer the potential to further improve access and outcomes, minimizing the short comings of one single form of therapy alone.

ABO Incompatible Renal Transplantation without Augmented Immunosuppression or Antibody Removal - Report of 10 Cases

Introduction: Many centres now perform renal transplants from live donors into ABO blood group incompatible (ABOi) recipients. Treatment protocols are varied but include some or all of pre-transplant rituximab, splenectomy, IVIG, T-cell depleting antibody induction, and antibody removal. The aim of such treatment is to reduce recipient ABO antibody titres to ‘safe’ levels (typically a titre of 1:8 or less) on the day of transplant. Here we report 10 successful ABOi transplants in patients with a baseline titre of 1:8 or less, none of whom received antibody removal or augmented immunosuppression. Methods: Between 2006 and 2011 20 patients have received an ABOi live donor transplant at our centre. In 10 of these the baseline IgG and IgM ABO antibody titres (measured using DiaMed gel-cards) were consistently 1:8 or less (1:8 for 3 patients, 1:4 for 3 and 1:2 for 4). Five of these patients were blood group O, with two A1, two A2 and one group B donor. The other 5 recipients were group A, with two AB and three B donors. Results: All patients received basiliximab induction followed by tacrolimus, MMF and prednisolone maintenance immunosuppression. All patients had primary graft function. There have been no episodes of either biopsy-proven or clinically determined rejection. 8 patients have stable graft function with a mean serum creatinine (SCr) of 111μmol/L (range 86-140) after 21 months follow up (2-74). One patient required ureteric reimplantation after a period of obstruction, and now has a stable SCr of 198μmol/L at 2 years follow up. The tenth patient has impaired graft function with SCr of 185μmol/L in the setting of very substantial weight gain. Conclusions: ABOi live donor renal transplantation can safely be performed without antibody removal or enhanced immunosuppression in patients with a baseline antibody titre of 1:8 or less. We suggest that ABO antibody titres should be measured in all patients with an ABOi live donor. We also believe that ABO antibody titres may usefully be measured in ABO group O patients on deceased donor waiting lists. ABOi kidneys could be offered to those with low titres, something that may be of particular benefit to HLA sensitized group O patients.

Transplantation for Acute Liver Failure: Report of Results in the Region of Castilla y Leon (Spain) After 10 Years of Activity

Acute liver failure is an uncommon disease but its overall mortality rate is still high without liver transplantation, which is the treatment of choice for patients achieving certain criteria. We have reported herein the experience and retrospectively analyzed results of liver transplantation for acute liver failure since the beginning of activity of our group, which is the only one in the region of “Castilla y Leon” (Spain). In 10 years, 14 patients underwent emergency transplantation among an overall series of 325 subjects. The patients were generally young men and women; the average wait list time was 2.14 days. The most common etiology was toxic exposure (no cases were related to acetaminophen overdose), followed by viral infection (all because of acute hepatitis B). Our posttransplant outcomes were: perioperative mortality, 0%; posttransplant in-hospital mortality, 14%; and 1-y, 3-y, and 5-year survival rates of 77.1%, 64.3%, and 64.3% respectively. Retransplantation rate was 7%. A major morbidity occurred in four patients: one primary dysfunction, one hyperacute rejection due to ABO blood group-incompatibility requiring retransplantation, two arterial complications, and two biliary leakages. Our outcomes of emergency transplantation were similar to those reported by both the European and Spanish Liver Transplantation Registries, despite the small number of patients.

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.

Early onset jaundice in the newborn: understanding the ongoing care of mother and baby

Neonatal hyperbilirubinaemia or jaundice is a relatively common condition in newborn babies presenting with changes to eythrocyte metabolism after day 3 of life. Early onset jaundice is less common and arises on day 1 from a pathological process. This paper outlines a case study of a baby presenting with this condition due to ABO blood group incompatibility who was admitted from the postnatal ward to the neonatal unit (NNU). The article will focus on the period after initial interventions on admission to the NNU and the ongoing care issues thereafter. Both clinical and psychoemotional care issues for the baby and family are raised. It is important that midwives understand what care is delivered during the neonatal unit stay so that they can empathise and assist with family coping strategies following the separation of the baby from the parents at an often emotionally charged time.

Is Flow Cytometry Crossmatch Analysis Using Sera with Different Dilutions Important for Pretransplant Analysis? A Case Report

The most effective form of treatment for chronic renal failure is kidney transplantation from a cadaver or a living donor. For a kidney transplant to be successful, tissue compatibility and a lack of donor-specific anti-human leukocyte antigen (HLA) antibodies in the circulation of the patient are vital, in addition to ABO blood group compatibility. The presence of anti-HLA antibodies is assayed before transplantation using various methods, but because organ rejections have been observed in previous studies, different techniques are required to detect anti-HLA antibodies. Today, flow cytometry crossmatching is one of the most important and effective techniques in testing for donor-specific anti-HLA antibodies (DSAs). If weakly positive serum is assayed after serial dilution, it can yield high positivity. Herein, we describe the differences between the results for diluted and undiluted weakly positive sera studied using the flow cytometry crossmatch (FCXM) technique. In a recent study, the sera of weakly FCXM-positive patients were diluted 1/50, and the FCXM test was repeated. The use of diluted serum eliminated the effect of the prozone so that the DSAs could be detected.

Clinical and laboratory characteristics and associated risk factors of infants hospitalized in newborn unit for indirect hyperbilirubinemia

Objectives: The aim of this study was to investigate characteristics of neonates hospitalized to Neonatal Unit due to indirect hyperbilirubinemia and to determine risk factors for indirect hyperbilirubinemia. Materials and methods: Totally 222 newborns, aged ≥35 weeks of gestational age and hospitalized in neonatal unit with indirect hyperbilirubinemia, were investigated. Physical examination and laboratory studies of children were performed. Decision of phototherapy and exchange transfusion was done according to total serum bilirubin (TSB) level that notified in the Guidelines of American Academy of Pediatrics. Results: Study group consisted of 131 (60%) male and 91 (30%) female newborns. No significant difference was found in TSB values between male and female neonates. There was 71.2% term and 19.8% late preterm newborn babies. Babies born with spontaneous vaginal delivery had borderline higher TSB values compared with cesarean section deliveries (p=0.051). ABO blood group incompatibility was found in 30.1% and Rh incompatibility in 6.7%. Insufficient nutrition and inadequate caloric intake were found in 49 (22.7%) of neonates, urinary tract infection in 19 (8.5%), hypernatremic dehydration in 9 (4.5%) and hypothyroidism in 4 (2.0%). Exchange transfusion was performed in 10 newborns and kernicterus occurred in two. A significant negative correlation was found between TSB values at hospitalization and baby’s birth (p<0.05) and a positive correlation between initial TSB value and percent of patient weight loss (p<0.05). Conclusions: According to our results, the most frequent etiological causes of jaundice in newborns were ABO blood group incompatibility, insufficient nutrition and being late preterm.

Outcome of exchange blood transfusions done for neonatal jaundice in Abakaliki, South Eastern Nigeria

Background:Neonatal jaundice (NNJ) is a major cause of morbidity and mortality among neonates in Nigeria and exchange blood transfusion (EBT) is a common modality of its treatment in Ebonyi State University Teaching Hospital (EBSUTH), Abakaliki. This communication aims to audit this service.Materials and Methods:A 3-year retrospective review of the case files of all neonates that had EBT for NNJ at the new born special care unit of EBSUTH.Result:Two hundred and thirty seven (17.25%) out of 1374 neonatal admissions had NNJ. EBT was performed for 40 (16.9%) of them. The commonest indications for EBT were low birth weight/prematurity, ABO blood group incompatibility, sepsis and glucose 6 phosphate deficiencies. The mean serum bilirubin at which EBT was done was 28.3 mg/dl. The EBT was uneventful in 36 cases while in four (10%) cases there were reported adverse events. Seven neonates (17.5%) died after the procedure and documented causes of death include bilirubin encephalopathy, respiratory failure, and septic shock and disseminated intravascular coagulopathy.Conclusion:There is high rate of EBT use in the management of severe neonatal hyperbilirubinemia with significant morbidity and mortality in this study site. There is need to review the contribution of factors such as late presentation in the hospital to this and proffer solutions to it.

Severe neonatal jaundice: Is it a rare event in Australia?

Hyperbilirubinaemia is common in the newborn period, and while the vast majority of babies are unaffected, significant neurological impairment remains a risk associated with extremely high levels of bilirubin. There is concern internationally that the number of babies affected by severe neonatal hyperbilirubinaemia may be increasing. This review describes the most current published data pertaining to the incidence and causes of severe neonatal hyperbilirubinaemia in order to determine whether concern regarding the possible re-emergence of kernicterus in Australia is warranted. Seven incidence studies conducted internationally between 1988 and 2005 identify an estimated incidence of severe neonatal jaundice of between 7.1 and 45 per 100,000 births and of kernicterus at 0.4-2.7. Major pathophysiological causes or associations include ABO and other blood group incompatibility, glucose-6-phoshate-dehydrogenase deficiency, infection and haemolysis of other causes including spherocytosis. Other factors associated with poor outcomes include prematurity, male gender, ethnicity, breastfeeding and early hospital discharge. The management of severe neonatal jaundice requires multifaceted risk quantification in addition to the availability of adequate surveillance, particularly in the context of early hospital discharge. It is of concern that currently there is a paucity of incidence data in Australia relating to this potentially devastating yet generally preventable condition. Therefore, a surveillance study has been initiated through the Australian Paediatric Surveillance Unit. It is anticipated that these data will accurately define the incidence in Australia and hopefully guide strategies to prevent a condition that we may have prematurely considered to be of historical interest only.

Single versus multiple dose intravenous immunoglobulin in combination with LED phototherapy in the treatment of ABO hemolytic disease in neonates

Intravenous immunoglobulin (IVIG) has been found to decrease hemolysis in neonatal jaundice due to blood group incompatibility, but a consensus on its usage has not been reached. We conducted a study to compare single versus multiple dose of IVIG in combination with light emitting diode (LED) phototherapy in patients with neonatal jaundice secondary to ABO blood incompatibility, and compared the efficacy of these treatments with that in a group of patients who received LED phototherapy solely. Thirty-nine term neonates with ABO blood group incompatibility were enrolled in the study. Group I received one dose of IVIG (1 g/kg) and LED phototherapy, and group II two doses of IVIG (1 g/kg) and LED phototherapy, whereas group III received LED phototherapy only. In group I, exchange transfusion was performed in one patient (6%) and in group II in one patient (10%). In the control group, none of the patients required exchange transfusion. Duration of LED phototherapy was 4.3 ± 0.7 days in group I + II (IVIG group), 3.9 ± 0.6 days in group III (P = 0.06). Lowest hematocrit level in group I + II was 35.0 ± 7.8 and group III was 38.9 ± 4.2, this was statistically significant (P = 0.034). IVIG therapy, single or multiple, did not affect exchange transfusion, need of erythrocyte transfusion and hospitalization time when used in combination with LED phototherapy in the treatment of ABO hemolytic jaundice in neonates.