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Although the electronic cross-matching of blood has been widely applied in some developed countries and regions, concern over the risk of undetected red blood cell (RBC) antibodies has limited its application in mainland China.This study was performed to explore the missed detection rate of RBC antibodies in a Chinese population from 2011 to 2016. If the results of 2 consecutive tests of ABO/RhD blood group identification were consistent and antibody screening results were negative, electronic cross-matching of the blood was performed. In addition, traditional serological cross-matching of blood (polybrene method) and a parallel experiment for electronic cross-matching of blood were performed to analyze the missed detection of unexpected RBC antibodies in blood donors and recipients.Using the polybrene method, 40,228 blood samples were tested by parallel traditional serological cross-matching of blood; among these samples, blood compatibility was found in 40,222 cases, primary incompatibility (incompatibility of the donor's erythrocytes with the recipient's serum) was found in 6 cases, and no secondary incompatibility was found. Identification of antibody specificity was performed using panel cells, and all unexpected RBC antibodies were confirmed as anti-Mur alloantibodies in the MNS system.Further improvements in the erythrocyte antigenic spectrum, especially the Mur antigen in Asian populations, are expected to ensure the safety of implementing electronic cross-matching in China.

Severe hemolytic anemia (HA) is an uncommon adverse reaction of intravenous immunoglobulin (IVIg) administration. Previous reports assume that antibodies contained in IVIg preparations are the cause of hemolysis. We report a 10-month-old infant with Kawasaki disease who was treated with high-dose IVIg and developed severe HA. The patient's Rh blood type was D+C+c+E-e+. He developed anti-C and anti-e antibodies following treatment with IVIg, and, after considering all possible causes of hemolysis, we concluded that this was a case of autoimmune HA induced by immunoglobulin treatment. The hyperinflammatory condition associated with Kawasaki disease may have contributed to the severity of anemia.

A 5-year-old male with sickle cell disease presented with pain, dark urine, and fatigue 10 days after a red blood cell (RBC) transfusion. Laboratory evaluation demonstrated severe anemia, blood type O+, and anti-D in the serum. Anti-D in a D+ patient led to RH genotyping, which revealed homozygosity for RHD*DAU4 that encodes partial D antigen. Anti-D in this patient whose RBCs exclusively express partial D caused a delayed hemolytic transfusion reaction after exposure to D+ RBCs. The finding of anti-D in a D+patient should be investigated by molecular methods to help distinguish an alloantibody from an autoantibody.

Objective: To estimate the potential economic benefit of reduced indirect antiglobulin screening for Rh(D)-negative pregnant women., Methods: A chart review of all Rh(D)-negative mothers delivering at the University of Washington from 2002 to 2012 was conducted to determine the rate of gestational seroconversion to anti-D antibodies before 28 weeks of gestation. A decision tree was constructed to estimate the economic effects of eliminating the indirect antiglobulin screen at 28 weeks of gestation and instead immunizing all Rh(D)-negative, anti-D antibody-negative women with anti-D immune globulin at that time. A theoretical cohort of 100,000 women was modeled. Probabilities and costs were derived from published literature, chart review, and expert opinion. Univariate sensitivity analyses followed by a Monte Carlo analysis examined assumptions and uncertainties in our model across entire distributions., Results: The seroconversion rate of development of anti-D antibodies before 28 weeks of gestation in the cohort analyzed was 0.099% (2/2,029 women). From a societal perspective, the expected cost savings from implementing the reduced indirect antiglobulin screening strategy, per 100,000 women, ranged from $6 to $7.7 million. The overall cost savings for implementing this strategy in the United States for 1 year ranged from $34.7 to $35.6 million. This strategy remained cost-beneficial when varying our parameters (eg, anti-D immune globulin, antibody test cost) to their logical extremes. The Monte Carlo analysis verified the cost savings of our strategy., Conclusion: The updated seroconversion rate and our model suggest that eliminating the 28-week antibody screen would be cost-beneficial from a societal perspective while posing minimal potential harm to the recipients.

Background: A woman's candidacy for Rh immune globulin depends on whether her blood type is Rh-positive (D antigen-positive) or Rh-negative (D antigen-negative). New molecular blood-typing methods have identified variant D antigens, which may be reported as Rh-positive or Rh-negative depending on the laboratory method. We describe a case illustrating the effect of the new laboratory methods on a woman's candidacy for Rh immune globulin and present recommendations for interpreting the new test results., Case: A 40-year-old woman presented for management of her third pregnancy. During her first pregnancy, she was typed as Rh-positive ("D") and did not receive Rh immune globulin. During her second pregnancy, she was typed as Rh-negative, in accordance with revised Rh-typing procedures. Anti-D antibody was detected. During her third pregnancy, she was genotyped as a partial D antigen, which was reported as Rh-negative., Conclusion: Revisions in laboratory procedures for Rh typing may present as a change in the Rh blood type of pregnant women-and as a change in their eligibility for Rh immune globulin.

Rhesus immune globulin has decreased the prevalence of rhesus D alloimmunization in pregnancy so that only approximately six cases occur in every 1,000 live births. The rarity of this condition warrants consideration of consultation with or referral to a maternal-fetal medicine specialist with experience in the monitoring and treatment of patients with red cell alloimmunization in pregnancy. Evaluation for the presence of maternal anti-D antibody should be undertaken at the first prenatal visit. First-time sensitized pregnancies are followed with serial maternal titers and, when necessary, serial Doppler assessment of the peak systolic velocity in the middle cerebral artery. In cases of a heterozygous paternal genotype, new DNA techniques now make it possible to diagnose the fetal blood type through free fetal DNA in maternal plasma. When there is a history of an affected fetus or infant, maternal titers are no longer predictive of risk in subsequent pregnancies. Serial peak middle cerebral artery velocities using Doppler ultrasonography can be used in these pregnancies to detect fetal anemia. In some situations, intrauterine transfusion is necessary through ultrasound-directed puncture of the umbilical cord with the direct intravascular injection of red cells. Perinatal survival rates of more than 90% have been reported; hydrops fetalis reduces the chance for a viable outcome by up to 11%. Neonatal and infant outcomes are complicated by the need for repeated transfusions secondary to suppressed erythropoiesis. Long-term studies have revealed normal neurologic outcomes in more than 90% of cases. Future therapy will involve selective modulation of the maternal immune system, making the need for intrauterine transfusions a rarity.

Purpose of Review: This review provides up-to-date information on the diagnosis and management of fetal anaemia., Recent Findings: Exciting advances in the field of red blood cell isoimmunization are phasing out the need for invasive procedures. Rhesus blood group genotyping using fetal DNA in maternal plasma has been introduced into clinical practice with remarkable success. The role of middle cerebral artery peak systolic velocity in screening for fetal anaemia has been confirmed in various causes of fetal anaemia. A recent review of a successful Iran national screening programme for thalassaemia provided a timely and valuable educational opportunity. The value of intrauterine transfusion as a treatment for fetal anaemia was demonstrated by both high success rate and low procedure-related pregnancy loss rate., Summary: Fetal anaemia is one of the severe fetal conditions that affect the worldwide population. Rhesus isoimmunization remains an important health issue despite the recommendation for anti-D immunoglobulin prophylaxis and injection after sensitizing events. Noninvasive ultrasound diagnostic methods have replaced traditional invasive procedures in the assessment of fetus at risk of anaemia due to various causes, including red blood cell isoimmunization, parvovirus B19 infection and thalassaemia. The increased availability of intrauterine transfusion will help to improve the prognosis of these anaemic fetuses.

Background: Hemolytic disease of the fetus and newborn caused by anti-G antibodies is rare, and in most previously reported cases, leads to a mild anemia. The RhG antigen is usually found in association with both RhD and RhC. We report a case of a twin pregnancy affected by both anti-G and anti-C alloantibodies leading to severe hemolytic disease of the fetus and newborn requiring multiple intrauterine transfusions and prolonged postnatal therapy., Case: A patient with a prolonged history of previously affected pregnancies due to anti-D and anti-C was subsequently found to be affected with anti-G instead. She required aggressive therapy during her pregnancy, initially with intravenous immune globulin and plasmapheresis until umbilical blood sampling and intrauterine transfusions were feasible., Conclusion: Although hemolytic disease of the fetus and newborn due to anti-G antibodies is rare and usually mild, these pregnancies should be followed up closely and in utero therapy should be offered if necessary.

One thousand five hundred consecutive live-donor renal transplants were performed in a single institution. Among these patients, 1,372 patients (group I) received Rh-identical allografts and 128 (group II) received Rh-nonidentical allografts. The two groups were homogenous apart from the prevalence of the Rh nonidentity among unrelated donor-recipient pairs. The rate of acute and chronic rejection was comparable in both groups (P = 0.33 for acute rejection and P = 0.66 for chronic rejection). The mean serum creatinine at 5 years was 1.8 +/- 1 mg/dL for group I and 1.7 +/- 0.9 mg/dL for group II (P = 0.5). The 1-, 5-, and 10-year graft survival rates were 94%, 78%, and 54% for group I and 95%, 82%, and 57% for group II. We found that the Rh(D) blood group system is not likely to be a clinically relevant histocompatibility barrier to live-donor renal transplantation.

Objective: To review cases of anti-c isoimmunization and determine the most appropriate management strategies., Methods: We performed a review of 102 pregnancies managed at The Ohio State University from 1967 to 2001 for anti-c isoimmunization. Of these, 55 had complete data and are included in this report. Information collected included serum titers, deltaOD450 values, Liley zones, fetal and neonatal hemoglobin levels and antigen typing, neonatal direct antiglobulin test, and neonatal outcomes. The appropriateness of traditional management was then evaluated., Results: Of the 55 pregnancies, 46 had fetuses with positive direct antiglobulin test, and nine pregnancies had unaffected fetuses. Of the affected neonates, 12 (26%) had serious hemolytic disease of the newborn. Of these 12, 8 required fetal transfusion, and the remaining 4 newborns had hemoglobin levels of less than 10 g/dL at the time of delivery. A titer of 1:32 or greater or the presence of hydrops fetalis identified all such fetuses. There were 58 amniocenteses performed for deltaOD450 When plotted on modified Liley graphs, deltaOD450 values corresponded to disease severity. There were no perinatal deaths attributable to anti-c hemolytic disease of the newborn., Conclusion: Anti-c isoimmunization might cause significant fetal and newborn hemolytic disease. A titer of 1:32 or greater or evidence of hydrops fetalis identified all the serious hemolytic disease at our institution. The significance of antibody titers and deltaOD450 values was similar to Rh-D sensitized pregnancies, and management by the same modalities is appropriate.

Background: Rare cases of hemolytic disease of the newborn occur in women with genetic variants of the D antigen. A partial D variant might be suspected when typing for the D antigen shows weaker-than-normal reactions (weak D). Historically, patients with a weak D phenotype have not been considered candidates for Rh immune globulin prophylaxis., Case: A gravida 2, para 1 woman with A-positive blood type, delivered an infant who died from severe hemolytic disease of the newborn 6 days after birth. Anti-D, undetectable at the first prenatal visit, was identified (titer 1:64) at delivery. The mother's red cells were partial D(VI) phenotype., Conclusion: Although severe hemolytic disease in patients with partial D is rare, this neonatal death illustrates the need for a change in management of women with weak D.

Prior to the 1970s and the advent of Rho (D) immune globulin (RIG) for Rh negative women, hemolytic disease of the newborn led to morbidity, long-term disabilities, and mortality. Antepartum RIG administration has been a standard of practice since 1983. Yet, Rh isoimmunization (sensitization) and its sequelae have not been completely eradicated. Rh-related issues remain clinical challenges facing perinatal and neonatal nurses. Evidence for the administration of RIG prenatally and during the postpartum period is presented including controversies and challenges. Current information about fetal and neonatal care of erythroblastosis fetalis and immune hydrops is also presented.

Previous reports, before the advent of cyclosporine, suggest that the small amount of blood transplanted with a kidney can result in rhesus D (RhD) antibody production. We looked for retrospective and current evidence of primary RhD antibody production following renal transplantation in RhD-negative recipients of an RhD-positive kidney. Of 42 patients, all on triple immunosuppressive therapy, 2 (5%) were found to have an RhD antibody identified for the first time after transplantation. As the number of pregnancies in transplant recipients increases, the small risk of primary immunization and subsequent risk of hemolytic disease of the newborn will become more important. Therefore, we recommend that all RhD-negative women of child-bearing age receiving an RhD-positive solid organ transplant are given a prophylactic dose of 500 IU of anti-D immunoglobulin intramuscularly at the time of transplantation.

The development and persistence of clinically significant red cell alloantibodies were studied in 1132 patients who underwent a heart and/or lung transplant at Harefield Hospital. Clinically significant antibodies were detected in 15 patients (1.3%) preoperatively and appeared in a further 15 (2.1%) of 704 patients followed up 1-404 weeks after surgery. Anti-D developed in only 1 of 52 D-negative recipients of a D-positive donor graft and in only 2 of 6 D-negative patients who were transfused with between 6 and 32 units of D-positive red cells. Most antibodies that appeared after transplantation remained detectable for only a few weeks. Antibodies detected preoperatively that reacted only with papain-treated cells became persistently undetectable in 4 patients who were transfused with red cells expressing the corresponding antigen specificity. By contrast, antibodies detected preoperatively by indirect antiglobulin test were still detectable after periods of up to 260 weeks in 4 patients who received only antigen-negative red cells. Immunosuppressive therapy appeared to profoundly affect the natural history of red cell alloantibody production in these patients. The underlying mechanisms warrant further study.

The story of Rho(D) immunoglobulin (RhoGAM) begins in 1909 with Theobald Smith, Fabyan Professor of Comparative Pathology at Harvard, and ends in the 1960s with completion of the clinical trials. Important in the development of RhoGAM were the search for a safe diphtheria vaccine, an interest in butterfly mimicry, the discovery of the Rhesus factor, and the contribution of Sing Sing prison inmates--seemingly unrelated occurrences. But, when all were combined, the riddle of erythroblastosis fetalis was solved.

The role of high-dose intravenous (IV) gamma globulin in the treatment of erythroblastosis fetalis was assessed in five pregnancies with severe Rh (four) or Kell (one) isoimmunization. These women were treated with IV gamma globulin (1.0 g/kg body weight) once a week. In addition, fetal blood transfusions were performed when indicated. In four patients with Rh sensitization, high-dose IV gamma globulin treatment had no apparent effect on the total number of intrauterine transfusions required, the interval between transfusions, or the volume of blood required at each transfusion. The treatment did not prevent fetal hydrops and had no effect on maternal antibody titers. In one patient with Kell sensitization, however, the course of the disease was less severe than anticipated, suggesting that IV gamma globulin treatment may have modified the severity of the disease. We conclude that high-dose IV gamma globulin does not appear to be useful in the treatment of severe Rh disease. Its role in Kell and other types of red-cell isoimmunization deserves further evaluation.

Nine pregnant women with Rh isoimmunization who delivered newborns with hydrops fetalis were studied. The placental proteins, pregnancy specific beta 1-glycoprotein (SP1), human placental lactogen, and placental protein 5 (PP5) were measured in maternal serum by radioimmunoassays. The results indicate that both the serum human placental lactogen and PP5 levels were significantly higher than those observed in normal pregnancy. The strikingly higher circulating PP5 levels found in all nine patients with Rh isoimmunization studied suggests that serum PP5 may be specifically elevated in pregnant patients with Rh isoimmunization and hydrops fetalis.

A case of primigravida in whom anti-C, anti-D, and anti-Kpb developed during the third trimester is described. Her first-born infant, delivered at 40 weeks' gestation, was mildly affected with hemolytic disease of the newborn and responded well to phototherapy. Her second-born infant, delivered at 36 weeks' gestation, had a positive direct antiglobulin test, but required no treatment. Clinical and laboratory aspects of both pregnancies are discussed.

Seventeen severely Rh-sensitized women were treated with promethazine hydrochloride (Phenergan) in 18 pregnancies, according to a protocol described by Gusdon et al. There was an unequivocal amelioration of the disease process in 10 of the pregnancies. In 9 of these 10 pregnancies, the infant survived. In 4 of the pregnancies, promethazine proved an unnecessary therapy as the infants were Rh negative. Promethazine may or may not have been helpful in 2 pregnancies, both of which resulted in live-born infants. One pregnancy resulted in intrauterine fetal death subsequent to an intrauterine transfusion. This infant was later shown to have multiple congenital anomalies incompatible with life. In a subsequent pregnancy, the mother was again treated with promethazine and had a normal infant who survived after exchange transfusions. The one loss of a live-born infant resulted from a cardiac arrest during an exchange transfusion. On the basis of these observations, the authors agree with Gusdon et al that promethazine does have an ameliorating effect on Rh-sensitized pregnancies.

The first American study on the incidence of gestational Rh0(D) sensitization is reported. The authors studied 3995 Rh0(D)-negative pregnancies from a population of 40,319 deliveries at Los Angeles-area Kaiser hospitals between 1976 and 1978. Among these were 61 Rh0(D)-sensitized pregnancies: 38 in women with prior sensitizations, 21 with gestational sensitizations, and 2 postpartum Rh0(D antigen) immune globulin (RhoGAM) failures. The incidence of gestational sensitization was 1.0% (21/2098). Cost-effectiveness of prophylactic RhoGAM post partum, prophylactic RhoGAM at 28 weeks' gestation, and Fetaldex testing post partum was analyzed. Prophylactic RhoGAM at 28 weeks' gestation was the most cost-effective method of further reduction of the Rh0(D) sensitization. All nonsensitized Rh0(D)-negative mothers who delivered Rh0(D)-positive fetuses received RhoGAM.

In a series of 1206 consecutive Rh-negative women who delivered Rh-positive infants, fetal erythrocytes were found in the maternal blood of 175 (14.5%) during the postpartum period. In 12 (1.0%) there was evidence of a larger fetomaternal hamorrhage than would be neutralized by a single 300-microgram dose of Rh-immune globulin. Except for manual removal of the placenta, no correlation was found between large fetomaternal hemorrhages and obstetric manipulations, complications, or surgery. Thus, the authors believe that all Rh-negative patients should be screened post partum to ascertain the adequacy of Rh-immune globulin prophylaxis.

Amniocentesis is a relatively safe and reliable procedure. However, there probably is a slightly increased risk of fetal loss following amniocentesis (approximately 0.5%). Other risks are minimal. Amniocentesis should be performed by obstetrician-gynecologists familiar with both the indications for the technique of second-trimester genetic amniocentesis. Recent social trends, including the increased availability of medical information to the lay public and the interest of many women in delaying childbearing, will increase public demand for antenatal diagnosis. It is important that obstetrician-gynecologists prepare to meet these demands.

Transfusion of one unit or more of Rh-positive red blood cells normally causes circulating anti-D antibody to appear 2-6 months later in 80-95% of Rh- persons. We asked whether transplant immunosuppression with cyclosporine and corticosteroids affects Rh immunization. Nineteen Rh- liver, heart, and heart-lung transplant recipients received 3-153 (median: 10) units of Rh+ RBCs at surgery and were tested for anti-D greater than 2 months later. Three patients developed anti-D at 11-15 days; one may have had an unusually rapid primary immune response and two were secondary to previous exposure by pregnancy. None of the other 16 patients had anti-D when tested 2.5-51 months later (13 patients, greater than 11.5 months). This low rate of Rhesus immunization in association with cyclosporine immunosuppression allows greater flexibility in meeting the transfusion needs of Rh- liver and heart transplant patients. Caution is still advised in young females and in patients who may have been previously exposed to Rh+ RBCs by transfusion or by pregnancy prior to the availability of perinatal Rh immune globulin twenty years ago. Other humoral immune responses to some vaccines or infectious agents may also be impaired in transplant patients.

A retrospective evaluation was undertaken of 78 Rh-negative women who underwent genetic amniocentesis without Rh-immune globulin prophylaxis. Of the 56 patients at risk for sensitization, 3 (5.4%) became sensitized during the pregnancy in which amniocentesis was performed. This number is not statistically different from the 2.1% incidence of spontaneous Rh immunization during pregnancy. However, a trend toward increasing sensitization after second-trimester amniocentesis was noted. As the fetoplacental blood volume at 16 weeks' gestation is approximately 12 to 13 ml, a 150-micrograms dose of Rh-immune globulin is recommended for the Rh-negative patient who is undergoing genetic amniocentesis.

The number of units of blood preoperatively crossmatched to the number of units transfused was studied retrospectively in patients undergoing four common obstetric and gynecologic procedures. Associated medical problems and the timing of and reasons for transfusions were evaluated. Patients with risk factors associated with an increased incidence of required transfusion were identified. Based on these results, a type and screen method for preoperative blood ordering is recommended for most patients undergoing cesarean section, abdominal hysterectomy, and vaginal hysterectomy. Using this method, sera are preoperatively tested for unexpected antibodies and ABO/Rh typing is done. If the antibody screen is negative, crossmatching is not done. Should a transfusion be ordered, crossmatching can be done in 20 minutes, or type-specific blood can be available after a 15-second saline spin. Through application of the type and screen method, a substantial savings in money and laboratory personnel time can be expected without compromising patient care.

Kidneys from an Rh-negative cadaver donor were transplanted to two Rh-positive patients. The donor's serum contained anti-Rho (D). In both patients, anti-Rho (D) was detected in their serum and on their red cells 3.5 weeks after transplantation. One patient had hemolysis. The antibodies persisted for nearly six months, despite graft rejection and nephrectomy in one case. These antibodies presumably arose from passenger B lymphocytes in the grafts from the Rh-immunized donor.

The indirect antiglobulin test was used to assess the efficacy of anti-D prophylaxis in two Rh negative women with hereditary persistence of fetal hemoglobin. Saturation of all D sites by passive antibody should be followed by indirect antiglobulin positivity due to excess administered anti-D. In hereditary persistence of fetal hemoglobin, all red cells have fetal hemoglobin making the acid elution test (Kleihauer-Betke smear) to detect feto-maternal hemorrhage useless. The indirect antiglobulin test is recommended in patients with hereditary persistence of fetal hemoglobin.