Challenge to ABO blood type barrier in living donor liver transplantation.

ABO incompatible living donor liver transplantation has the potential to expand the donor pool for patients with end stage liver diseases on the expense of challenges to overcome immunological barriers across blood type. There is a profound impact of age on incidence and severity of antibody mediated rejection (AMR). Even children older than 1 year have chances of AMR; children aged 8 years or older have risks of hepatic necrosis similar to adult liver recipients. The mechanism of AMR is based on circulatory disturbances secondary to inflammation and injury of the vascular endothelium caused by an antibody-antigen-complement reaction. The strategy to overcome ABO blood type barrier is based on both pre-transplant desensitization and adequate treatment of this phenomenon. Nowadays, rituximab is the standard means of desensitization but unfortunately an insufficient aid to treat AMR. Because of low incidence (less than 5% in the rituximab era), in practice of AMR only some case reports about the treatment of clinical AMR are available in the literature. Initial experiences revealed that the proteasome inhibitor, bortezomib might be a promising treatment based on its capacity to deplete plasma cell agents. Although ABO blood type barrier has been counteracted in 95% of patients by applying "rituximab-desensitization", many issues, such as prediction of high-risk patients of infection and AMR and secure treatment strategies for evoked AMR, remain to be resolved.

Unusual cause of severe neonatal hyperbilirubinaemia: a twin case.

We present twins born to the 31-year-old, multigravida mother, who were referred to our centre at 90 hours of life for severe hyperbilirubinaemia. Twin 1 had already received two double volume exchange transfusions at 55 and 83 hours of life, in view of the persistent rise in bilirubin despite receiving phototherapy. Twin 2 had received phototherapy and 1 packed red blood cell transfusion in view of the fall in haematocrit. Mother's blood group was B positive and that of both twins was O positive. Both the twins were started on intensive phototherapy and their serum bilirubin and haematocrit were evaluated. On investigation, a minor blood incompatibility was found. Double volume exchange transfusion was done for twin 2 at 100 hours of life in view of the rapid rise in serum bilirubin. Both the babies were monitored for their serum bilirubin and treated for sepsis and discharged after 15 days.

ABO blood group incompatibility and infertility: still an open debate.

Now as before, there's controversy in the field of immunoreproduction.

Flow Cytometry in Detection of Fetal Red Blood Cells and Maternal F Cells to Identify Fetomaternal Hemorrhage.

Accurate detection and quantitation of fetomaternal hemorrhage (FMH) is critical to the obstetric management of rhesus D alloimmunization in Rh-negative pregnant women. The flow cytometry is based on the detection of fetal red blood cells using a monoclonal anti-HbF antibody, and is the method most indicated for this estimation. The objective of this study was to quantify fetal red blood cell levels of pregnant women using flow cytometry. We analyzed 101 peripheral blood samples from Rh-negative and Rh-positive women, whose mean age was 24 years (20-32 years), after vaginal delivery or cesarean section. Our study showed that 53% of pregnant women had fetal red blood cells levels <2.0 mL, 31% between 2.0-3.9 mL, 16% between 4.0-15.0 mL, and 1% >15.0 mL. Accurate quantitation of fetal red blood cells is necessary to determine the appropriate dose of anti-D (RHD) immunoglobulin to be administered to pregnant or postpartum women.

Exposure to ABO-nonidentical blood associated with increased in-hospital mortality in patients with group A blood.

BACKGROUND: Transfusing ABO-compatible blood avoids most acute hemolytic reactions, but donor units that are ABO compatible are not necessarily ABO identical. Emerging data have raised concerns that ABO-nonidentical blood products lead to adverse outcomes. STUDY DESIGN AND METHODS: A large multihospital registry (Transfusion Registry for Utilization, Surveillance, and Tracking) was used to determine the association between exposure to ABO-nonidentical blood and in-hospital mortality. Cox regression analyses controlled for sex, age, hemoglobin, creatinine, and in-hospital interventions and stratified by age of blood and admission year. RESULTS: Data from 18,843 non-group O patients admitted between 2002 and 2011 and receiving at least 1 unit of blood were analyzed. Overall, group A patients had significantly increased risk of in-hospital death upon receiving a nonidentical unit (RR , 1.79; 95% CI, 1.20-2.67; p = 0.005). There was no evidence of increased risk for group B or AB patients. Similar results were seen when only patients with circulatory disorders were considered. When patients with an injury or poisoning diagnosis were excluded, the risk of in-hospital death after receiving a non-identical unit was significantly higher in group A patients and significantly lower in Group B patients. CONCLUSION: Our study demonstrates an adverse effect of ABO-nonidentical blood in a broad range of patients with group A blood, after adjustment for potential confounders. Further research in this area is required to study possible mechanisms. Increased mortality associated with exposure to nonidentical blood in these patients would have a substantial impact at the population level; it would challenge how blood suppliers manage inventory and recruit donors and how health care providers administer blood.

Blueberry muffin rash, hyperbilirubinemia, and hypoglycemia: a case of hemolytic disease of the fetus and newborn due to anti-Kp(a).

Hemolytic disease of the fetus and newborn occurs when maternal IgG antibodies cross the placenta and cause hemolysis of fetal red blood cells. Kp(a) is a low frequency red blood cell antigen that has rarely been implicated in hemolytic disease of the fetus and newborn. The few reported cases attributed to anti-Kp(a) have typically had minimal clinical consequences. We report a critically ill neonate who presented with purpura, respiratory failure, severe liver dysfunction, hyperbilirubinemia, hypoglycemia and anemia. This case report broadens the spectrum of neonatal disease associated with anti-Kp(a), addresses the evaluation of hemolysis with liver failure in a neonate, and emphasizes the importance of screening for antibodies to low frequency red blood cell antigens in suspected hemolytic disease of the fetus and newborn.

Fetal intraperitoneal injection of immunoglobulin diminishes alloimmune hemolysis.

We report a case of severe fetal anemia associated with maternal anti-M antibody that was treated by direct injection of pooled human immunoglobulin into the fetal abdominal cavity. Four treatments at a dosage of 2 g per-kg estimated fetal body weight were performed, and no side effects were observed. A healthy baby girl was delivered transvaginally at 38 weeks, with neither exchange transfusion nor phototherapy required. Follow-up over 12 months found no indications of anemia or developmental delay in the child. This is believed to be the first report of fetal anemia in a blood-type-incompatible pregnancy being treated successfully with only direct immunoglobulin injection into the fetus. The immunoglobulin may have functioned as a neutralizing antibody causing the anemia to improve.

Possible suppression of fetal erythropoiesis by the Kell blood group antibody anti-Kp(a).

Antibodies to antigens in the Kell blood group system are usually immunoglobulin G, and, notoriously, anti-K, anti-k, and anti-Kp(a) can cause severe hemolytic transfusion reactions, as well as severe hemolytic disease of the fetus and newborn (HDFN). It has been shown that the titer of anti-K does not correlate with the severity of HDFN because, in addition to immune destruction of red blood cells (RBCs), anti-K causes suppression of erythropoiesis in the fetus, which can result in severe anemia. We report a case involving anti-Kp(a) in which one twin was anemic and the other was not. Standard hemagglutination and polymerase chain reaction (PCR)-based tests were used. At delivery, anti-Kp(a) was identified in serum from the mother and twin A, and in the eluate prepared from the baby's RBCs. PCR-based assays showed twin A (boy) was KEL*841T/C (KEL*03/KEL*04), which is predicted to encode Kp(a+b+). Twin B (girl) was KEL*841C/C (KEL*04/KEL*04), which is predicted to encode Kp(a­b+). We describe the first reported case of probable suppression of erythropoiesis attributable to anti-Kp(a). One twin born to a woman whose serum contained anti-Kp(a) experienced HDFN while the other did not. Based on DNA analysis, the predicted blood type of the affected twin was Kp(a+b+) and that of the unaffected twin was Kp(a­b+). The laboratory findings and clinical course of the affected twin were consistent with suppression of erythropoiesis in addition to immune RBC destruction.

Middle cerebral artery-peak systolic velocity in dizygotic twins with anti-E alloimmunization.

Middle cerebral artery-peak systolic velocity (MCA-PSV) has been reported to predict fetal anemia with similar accuracy as amniotic ΔOD450 assay. Alloimmunized dizygotic twin pregnancy allows us to compare anemic and non-anemic twins in the same intrauterine environment. We herein present a case of Rh (E)-incompatible dizygotic twin pregnancy, where MCA-PSV could precisely detect the anemia in one of the twins. A 36-year-old woman, whose previous child required exchange transfusion due to hemolytic anemia of newborn (HFDN), conceived twins after in vitro fertilization-embryo transfer. At 24 weeks' gestation, MCA-PSV of twin A and twin B were 23.9 cm/s (0.8 multiples of median; MoM) and 30.7 cm/s (1.0 MoM), respectively. At 31 weeks' gestation, MCA-PSV values of both twins were sharply elevated to nearly 1.4 MoM. Thereafter, MCA-PSV of twin A fell to 1.0 MoM, whereas MCA-PSV of twin B exceeded 1.5 MoM at 34 weeks' gestation. Development of fetal anemia was suspected and emergency cesarean section was performed. Twin B showed moderate anemia with positive direct Coombs' test and was diagnosed as HFDN due to anti-E alloimmunization. Twin B required phototherapy and red cell transfusion, but exchange transfusion was safely obviated.

ABO-incompatible heart transplantation in infants: analysis of the united network for organ sharing database.

INTRODUCTION: ABO-incompatible heart transplantation, traditionally contraindicated because of the risk of hyperacute rejection, has been used selectively in recent years. Infants have limited production of isohemagglutinins, which may lower the risk of hyperacute rejection. A large national database was used to analyze the effect of ABO incompatibility on outcomes after heart transplantation in infants. METHODS: Heart transplant recipients aged younger than 1 year reported to the United Network for Organ Sharing from 1999 to 2007 were divided according to donor-recipient ABO incompatibility or compatibility. Outcomes included Kaplan-Meier survival and hyperacute rejection. Propensity-adjusted Cox regression modeling was used to identify predictors of mortality. RESULTS: Of 591 infants that underwent heart transplantation, 35 (6%) received allografts from ABO-incompatible donors. ABO-incompatible recipients trended toward more congenital heart disease (71% vs 66%; p = 0.06) and were less likely to have dilated cardiomyopathy (11% vs 29%; p = 0.02). One ABO-incompatible infant had hyperacute rejection requiring retransplantation. No ABO-incompatible infant and 2 ABO-compatible infants died from hyperacute rejection. Survival was similar at 3 years. Propensity-adjusted Cox regression analysis demonstrated that ABO-incompatibility did not predict mortality (hazard ratio, 3.61; 95% confidence interval, 0.26-49.0; p = 0.33). CONCLUSION: ABO-incompatible heart transplantation can be performed safely in infants without greater incidence of hyperacute rejection. ABO-incompatible heart transplantation should be strongly considered in infants to maximize donor organ utilization and reduce waiting-list mortality.

Proteomic analysis of human amniotic fluid from Rh(-) pregnancy.

BACKGROUND: The objective of this study was to identify proteins from the amniotic fluid of the most common reproductive ailment, that is, Rh(-) incompatibility. In the present study, AF from Rh(-) pregnancy in the 29-35th week of gestation was analyzed by 2-DE, and our purpose was to identify the major spots on 2D gel. METHODS: Proteins from an amniotic fluid sample was separated on 2D gel and visualized after silver staining. Most of the spots were analyzed by MALDI-TOF/MS, and were identified based on the NCBI database by a peptide mass fingerprinting method. RESULTS: Albumin, serotransferrin, haptoglobin, alpha-fetoprotein and immunoglobulin were the major proteins detected. On comparison with 2D gel of normal AF, differences were observed at the level of albumin, and newly identified Calgranulins and Neutophil-defensins were observed. Many enzymes, growth factor binding proteins, protease inhibitors and proteins related to inflammation have also been identified. CONCLUSIONS: This study demonstrates, for the first time, the potential utility of proteomics-based approaches to identify specific biomarkers like Calgranulins and Neutophil-defensins and diagnostic profiles for Rh(-) incompatibility processes and pathophysiologic conditions of pregnancy.

Six consecutive cases of successful adult ABO-incompatible living donor liver transplantation: a proposal for grading the severity of antibody-mediated rejection.

BACKGROUND: The clinical symptoms, histological findings, and treatments for antibody-mediated rejection (AMR), which is the leading cause of graft loss in adult ABO-incompatible liver transplantation (ABO-I-LT), have rarely been discussed. METHODS: We performed adult living donor ABO-I-LT on six patients. We used anti-CD20 monoclonal antibody combined with plasma exchange preoperatively and intraportal or hepatic-arterial infusion, consisting of prostaglandin E1, corticosteroids, and protease inhibitor postoperatively to prevent AMR. Splenectomy was performed in patients 1, 4, 5 and 6 but not in patients 2 and 3. Weekly liver biopsies were performed after ABO-I-LT. When severe AMR was diagnosed, we performed plasma exchange combined with gamma-globulin bolus infusion (PE+IVIG). RESULTS: In patients 1-3, severe jaundice, rapid decreases in platelet counts, and severe coagulopathy were observed in the early postoperative period. Liver biopsies sampled after the onset of these clinical findings were characterized by severe periportal and lobular hemorrhagic and neutrophil infiltration, suggesting that severe AMR occurred. However, after the initiation of PE+IVIG, AMR was remedied in all three patients. In patients 4-6, severe AMR was not observed. Mild AMR characterized by mild portal hemorrhagic infiltration was observed in patient 4, and moderate AMR characterized by moderate periportal and lobular hemorrhagic infiltration was observed in patient 6. Patients 4-6 did not require PE+IVIG and their clinical course was uneventful. CONCLUSION: Given the experience of these six patients, we consider that AMR may be graded based on liver biopsy findings including hemorrhagic infiltration and neutrophil infiltration, as well as clinical findings. All six patients are currently doing well.

Placental drainage of fetal blood at cesarean delivery and feto maternal transfusion: a randomized controlled trial.

OBJECTIVE: To assess the efficacy of placental drainage of fetal blood at the time of cesarean delivery on the incidence of feto-maternal transfusion. METHODS: This randomized trial includes 86 gravid women who underwent cesarean delivery. Forty-four women were assigned to the placental drainage group and 42 to the no-drainage group. Placental drainage was accomplished by cutting and milking the umbilical cord until no further blood flow occurred. All placentas were spontaneously expelled. The primary outcome variable, as assessed by preoperative and postoperative Kleihauer-Betke tests, was the amount of fetal blood (greater than or equal to 0.5 mL) in the maternal circulation. RESULTS: The group having placental drainage of fetal blood before placental delivery showed a significantly lower incidence (3 of 44, 6.8%) of feto-maternal transfusion (P=.003) as compared with the undrained group (14 of 42, 33%; relative risk 0.20, 95% confidence interval 0.065-0.65; number needed to treat=4). CONCLUSION: Placental drainage of fetal blood before spontaneous placental delivery at the time of cesarean delivery significantly reduces the incidence of feto-maternal transfusion. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00470899 LEVEL OF EVIDENCE: I.

Rh alloimmunization and term delivery.

Nowadays management of severe Rh alloimmunization consists of serial determination of middle cerebral artery peak systolic velocity, amniocentesis, cordocentesis, and in many instances intrauterine transfusion. We present a case of severe Rh alloimmunization who, for the first time in Iran, was delivered at term after several intrauterine transfusions.

Repeat ABO-incompatible platelet transfusions leading to haemolytic transfusion reaction.

A 65-year-old woman, blood group A RhD positive, who had completed her first course of induction chemotherapy for acute myeloid leukaemia was transfused with apheresis platelets over a number of days. On three occasions she received group O RhD positive units, which had been screened and found not to contain high-titre anti-A,B isoagglutinins. Following the third unit, she developed a haemolytic transfusion reaction and died soon thereafter. This has led to change in policy of the supplying centre in testing for high-titre anti-A,B isoagglutinins. Blood group O apheresis platelets and fresh-frozen plasma units are now labelled as high titre with a cut-off of 1/50 as compared to the previous cut-off of 1/100 for anti-A,B isoagglutinins. A universal approach to testing donations for high-titre anti-A,B isoagglutinins, better compliance of guidelines and monitoring of patients is necessary.

[Blood transfusion safety: current progress]. / Sécurité transfusionnelle: contribution des progrès réalisés.

For the past ten years, a real improvement in knowledge and methods concerning blood transfusion safety has been made. In this observation, concerning a polytraumatism patient who received massive blood transfusion with no immunologic nor infectious complications occurring one year later, brings evidence of real progress on blood transfusion safety for improvement in short and long term prognosis for polytransfused patients.

Plasma exchange conditioning for ABO-incompatible renal transplantation.

The supply of deceased donor kidneys is inadequate to meet demand. To expand the pool of potential donors, ABO-incompatible transplants from living donors have been performed. We present the Mayo Clinic experience with such transplants. Enrollment was open to patients when the only available potential living kidney donor was ABO-incompatible. Conditioning consisted of plasma exchanges followed by intravenous immunoglobulin. Splenectomy was performed at the time of transplant surgery. Post-transplant immunosuppression consisted of anti-T lymphocyte antibody, tacrolimus, mycophenolate mofetil, and prednisone. Isoagglutinin titers and scores were determined before and after each plasma exchange. Transplant outcomes were determined. Twenty-six ABO-incompatible transplants were performed. No hyperacute rejection occurred. Mean patient follow-up was 400 days. Patient and graft survivals at last follow-up were 92 and 85%, respectively. Antibody-mediated rejection occurred in 46% and was apparently reversed in 83% by plasma exchange and increased immunosuppression. The initial plasma exchange reduced immediate spin and AHG hemagglutination reactivity scores by 53.5 and 34.6%, respectively. Over the course of the pretransplant plasma exchanges, the immediate spin and AHG hemagglutination reactivity scores decreased by 96.4 and 68.5%, respectively. At 3 and 12 months, the immediate spin and AHG hemagglutinin reactivity scores and titers were less than those at baseline but greater than or equal to those on the day of transplantation. Despite an increase in scores and titers, antibody-mediated rejection was not present. Pre-transplant plasma exchange conditioning combined with other immunosuppressives can be used to prepare patients for ABO-incompatible kidney transplantation from living donors, but antibody-mediated rejection post-transplant is a common occurrence and allograft survival may be reduced. Controlled clinical trials are needed to identify the optimum conditioning for ABO-incompatible renal transplants.