Anemic Disease of the Newborn With Little Increase in Hemolysis and Erythropoiesis Due to Maternal Anti-Jra: A Case Study and Review of the Literature.

The severity of the hemolytic disease of the fetus and newborn (HDFN) due to Jra mismatch ranges from no symptoms to severe anemia that requires intrauterine and exchange transfusions. We encountered a newborn, born to a healthy mother having anti-Jra at 38 weeks of pregnancy, who had moderate anemia, a positive direct antiglobulin test (DAT) result, no increased erythropoiesis, and no jaundice at birth. Flow cytometry revealed that the Jra antigen of red cells in the infant was nearly negative at birth, biphasic at 5 weeks, and lowly expressed at 7 months of life. We searched online for previous case reports on HDFN due to Jra incompatibility. Among 63 reported cases, excluding 25 cases, 38 were included with the present case for analysis. Of 39 newborns, 10 developed clear anemia (hemoglobin <10.0 g/dL), and 1 died, 5 developed hydrops fetalis, 4 needed intrauterine transfusion and/or exchange transfusion, and 3 received red cell transfusion after birth; overlaps were included. Among 29 neonates with no anemia, 8 needed interventions including phototherapy and γ-globulin infusion, and the remaining 21 received conservative supports only. The maternal anti-Jra titer, ranging between 4 and 2048, did not correlate with the severity of anemia, levels of bilirubin, or any interventions required. The DAT of red cells was positive in 29 of 36 fetuses/newborns tested, whereas it was often negative among anemic neonates (4 of 9) (P < .05). Hematopoiesis did not increase effectively, as indicated by reticulocyte ratios between 1.7% and 22.3%, even with the increase in reticulocytes in anemic neonates compared with nonanemic neonates (P < .05). Total bilirubin levels ranged broadly between 0.2 and 14.3 mg/dL but were generally low. The maternal anti-Jra titer and IgG3 subclass did not correlate with the morbidity of the newborns. Being identical/compatible between mothers and their infants may possibly enhance infants' morbidity, as a weak tendency was observed (P = .053). Maternal anti-Jra may suppress erythropoiesis in fetuses via a mechanism different from the established HDFN, such as anti-D, as evidenced by the lower reticulocyte count and small increase in bilirubin in neonates. As the anti-Jra titer, IgG subclass, and DAT were not correlated with the severity, the mechanism of anti-Jra-induced HDFN remains to be elucidated.

Retrospective analysis of HDFN due to ABO incompatibility in a single institution over 6 years.

OBJECTIVES: To study the rate of ABO haemolytic anaemia of fetus and newborn (HDFN) in one institution over 6 years. BACKGROUND: ABO major incompatibility between mothers and their newborns occurs in about 10% of births. So, mothers with an O blood group may form IgG-class antibodies against A and B antigens, which could pass across the placenta and lead to a variable degree of HDFN in the newborn. METHODS: At our institution, we have reviewed data regarding ABO-based HDFN in the last 6 years. RESULTS: We found that, in 28 089 deliveries, an ABO major incompatibility between mothers and newborns occurs in 11% of cases, with 72% of O/A and 28% of O/B incompatibility. In turn, 23% of these newborns had an eluate-confirmed positive direct antiglobulin test [DAT; 74% (511) were due to anti-A and 26% (179) to anti-B], with 1·0% requiring invasive treatments (exchange transfusion or intravenous immunoglobulin). Overall, 2·5% of the total newborns had a positive DAT for an anti-A or anti-B antibody, and 0·11% required invasive treatment in addition to phototherapy for their HDFN. CONCLUSIONS: Serological ABO HDFN is a relatively frequent event when an O-A/O-B incompatibility between mothers and their newborn occurs and, in most cases, translates into a self-limiting disease, with a small number of newborns requiring invasive treatments. The DAT test, although not predictive of disease severity, appears to be a useful tool to monitor babies born from O-A/O-B-incompatible pregnancies and to identify those who may require treatment.

Severe ABO Hemolytic Disease of the Newborn Requiring Exchange Transfusion.

ABO incompatibility (ABOi), the most common cause of hemolytic disease of the newborn (HDN), is nearly always mild and treatable with phototherapy. Reports of ABOi HDN requiring neonatal exchange transfusion are extremely rare since the inception of modern guidelines. Here, a case of ABOi HDN clearly met criteria for exchange transfusion. An O-positive African American mother delivered a B-positive neonate that quickly developed hyperbilirubinemia. The neonatal DAT was positive from anti-B and anti-A,B, and maternal IgG titer was 1024. Double volume exchange transfusion resulted in a favorable outcome. Given early discharge of newborns, further understanding of factors predicting severe disease is needed.

[Positive Coomb's test in newborns; causes and clinical consequences Summary of cases diagnosed in the Blood Bank in the years 2005 to 2012].

INTRODUCTION: Hemolytic disease of the fetus and newborn (HDFN) is caused by the destruction of fetal red blood cells due to red cell antibodies produced by the mother. HDFN can cause fetal hydrops during pregnancy or neonatal jaundice after birth. Direct Antiglobulin Test (DAT) detects antibodies bound to red cells and is a valuable test aiding in the diagnosis of HDFN. In Iceland DAT is routinely performed on cord blood or newborn blood samples if the mother is Rhesus D negative or has non-A/B red cell alloantibodies. The aim of this study was to investigate the causes and consequences of positive DAT in newborns in Iceland over a period of eight years. MATERIAL AND METHODS: The study population was infants diagnosed with a positive DAT in the Blood Bank in Iceland in the years 2005-2012. Relevant data on the blood group and antibody status of mother and child, blood transfusion and DAT results were retrieved from the Blood Bank information system ProSang. Birth records provided information on birth weight, gestational age and phototherapy. Health records from the Children's Hospital provided information on the management and fate of the newborn. RESULTS: Over the study period 383 newborns had a positive DAT result at the Blood Bank. In 73.6% of cases the underlying cause was ABO blood group mismatch between mother and infant, in 20.4% of cases the mother had non-A/B red cell alloantibodies, in 3.9% both of above factors were present, while in 2.1% the cause was unclear. A total of 179 (47.6%) children had neonatal jaundice that required treatment, of which 167 (93.3%) only needed phototherapy. Eight infants required exchange transfusion, five of these had Rhesus antibodies and three ABO blood group mismatch. CONCLUSION: ABO blood group mismatch between mother and child was the most common cause for a positive DAT in neonates in Iceland in the years 2005-2012. Almost half of the neonates required treatment but usually phototherapy was sufficient. Rarely, blood transfusion or exchange transfusion was necessary in severe cases of ABO blood group mismatch or non-A/B red cell alloantibodies. KEY WORDS: Coombs test, Direct Antiglobulin Test (DAT), Hemolytic disease of the fetus and newborn (HDFN), ABO blood group mismatch, red cell alloantibodies, neonatal jaundice, exchange transfusion. Correspondence: Anna Margret Halldorsdottir, annamha@landspitali.is.

[Difficulties of the care of public antigen alloimmunization]. / Difficultés de la prise en charge de l'allo-immunisation anti-public.

Alloimmunization against high-frequency erythrocyte antigens is a problematic situation in terms of laboratory diagnosis, transfusion and obstetrical management. We report the case of a pregnant woman alloimmunized against public Ag. We detail the difficulties of alloantibody (Ab) identification and transfusion management of the deliveries. A 29-year-old pregnant woman was hospitalized in gynecology and obstetrics departments at 36 weeks of gestation for assessment of hydrops fetalis. Antibody identification test revealed the presence of a pan-reactive antibody. Investigations realized in CNRGS (Paris) concluded in anti-GE2+anti-RH3+autoantibody. The red cell phenotype was GE: -2,3. A therapeutic interruption of the pregnancy was indicated. A program of autologous transfusion was organized with withdrawal of 2 units of blood. The 2nd pregnancy took place normally. Before delivery, an autologous blood reserve consisting of 2 red cell packs and 2 fresh frozen plasma was withdrawn and transfused after delivery. The management of anti-public alloimmunization poses several problems. The first one is of diagnostic nature with, on the one hand, the difficulty of Ab identification by the available red cell panels and, on the other hand, the possible presence of alloantibodies of transfusional or obstetric interest masked by anti-public Ab. The second is represented by transfusional care of these patients. In the absence of a national reserve of frozen rare blood, the autologous transfusion remains the only alternative. However, it can answer only a limited number of indications and only in case of moderate blood loss.

The role of carboxyhemoglobin measured with CO-oximetry in the detection of hemolysis in newborns with ABO alloimmunization.

OBJECTIVES: To evaluate carboxyhemoglobin (COHb) values measured with a CO-oximeter (Roche-cobas b 221) in jaundiced newborns with or without hemolysis and healthy controls in order to assess whether COHb measurement determined with a CO-oximeter could be used as an indicator of hemolysis in newborns with ABO alloimmunization. METHODS: A total of 86 term newborn infants were prospectively studied. The study cohort consisted of three subgroups: 18 infants with ABO HDN, 21 infants with hyperbilirubinemia without hemolytic disease who required phototherapy, and 47 healthy controls. The COHb, bilirubin, and Hb levels were measured. RESULTS: The three subgroups did not differ significantly with respect to birth weight, gestational age, gender, Apgar score, or mode of delivery. The ABO HDN infants had significantly higher COHb values than the healthy controls (median 2.4% versus 1.3%, p < 0.0005) and the group with hyperbilirubinemia without hemolytic disease (median 2.4% versus 1.3%, p < 0.0005), although the infants with hyperbilirubinemia without hemolytic disease did not have significantly higher COHb values compared with the healthy controls. The cut-off value of 1.7% COHb had 72% sensitivity and 97% specificity for confirming hemolysis in ABO alloimmunization. CONCLUSIONS: Our data show that COHb values determined with CO-oximeters are higher in newborns with hemolysis than in those without hemolysis. COHb measured with CO-oximeters could be used to confirm hemolysis in infants with ABO alloimmunization.

Variable Clinical Presentations of ABO Incompatibility in Dizygotic Twins.

Newborns with ABO blood group incompatibility can have a spectrum of clinical presentations from remaining asymptomatic to severe hemolytic anemia with jaundice. This case presentation discusses dizygotic twins who demonstrated both ends of the clinical spectrum. Similar cases in which there is such extreme variation between twins were not attainable in the current literature, which prompted the authors to present it as a rare occurrence and one that was unexpected based on their past experience with ABO incompatibility both in singletons and in twins.

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

BACKGROUND: 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. MATERIAL AND METHODS: 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). RESULTS: 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. DISCUSSION: 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.

Acute kernicterus in a neonate with O/B blood group incompatibility and a mutation in SLC4A1.

We cared for a term female newborn, who at 108 hours of age, with a total serum bilirubin of 15.4 mg/dL, was discharged from the hospital on home phototherapy. At a return appointment 44 hours later, her total serum bilirubin was 41.7 mg/dL and signs of acute kernicterus were present. Maternal/fetal blood group O/B incompatibility was identified, with a negative direct antiglobulin test, which was positive on retesting. She had abundant spherocytes on blood smear, and these persisted at follow-up, but neither parent had spherocytes identified. A heterozygous SLC4A1(E508K) mutation (gene encoding erythrocyte membrane protein band 3) was found, and in silico predicted to result in damaged erythrocyte cytoskeletal protein function. No mutations were identified in other red cell cytoskeleton genes (ANK1, SPTA1, SPTB, EPB41, EPB42) and the UGT1A1 promoter region was normal. Neurologic follow-up at 2 and 4 months showed developmental delays consistent with mild kernicterus.

Outcome and cost analysis of implementing selective Coombs testing in the newborn nursery.

OBJECTIVE: (1) To determine whether infants born to O+ mothers who had selective cord-blood testing would have higher rates of clinically significant hyperbilirubinemia compared with those newborns who had routine cord-blood testing. (2) To determine the amount of cost savings by implementing a policy of selective cord-blood testing in newborns born to O+ mothers. STUDY DESIGN: We conducted a retrospective pre/post intervention chart review on all infants in the normal newborn nursery at Loyola, born to blood type O+ women between 1 April 2008 and 1 April 2009. The pre-intervention group (routine testing) included infants born within 6 months before implementation of a new policy. The post-intervention group (selective testing) included infants born within 6 months following the implementation of a new policy. Data were collected for each of these groups regarding clinically significant hyperbilirubinemia. RESULT: All 250 of the infants in the routine testing group had a cord-blood type and Coombs done, whereas 42 of 164 (25%) infants in the selective group had testing done. By the end of the 6 months following the policy change, only 8% of infants were undergoing cord testing. When comparing routine vs selective testing, there was no statistically significant difference in the 24-h serum bilirubin, rate of phototherapy during the birth hospitalization, rate of readmission for hyperbilirubinemia or peak serum bilirubin level at readmission. The 92% reduction of cord-blood typing and Coombs testing would lead to a cost saving of $4100 per year to our hospital and $18 900 per year to our patients, and 95 h per year of technician time to perform these tests. When extrapolated to Illinois births in 2008, this would lead to an annual cost saving of almost $800 000 to Illinois hospitals and about $3.6 million to patients. CONCLUSION: Selective newborn cord testing of infants born to O+ mothers can decrease the use of resources and costs without increasing the risk of clinically significant hyperbilirubinemia.

Anti-T haemolysins: the effects of sialic acid removal and 2-aminoethylisothiouronium bromide treatment of erythrocytes on immune lysis.

BACKGROUND AND OBJECTIVES: Intravascular haemolytic reactions are reported in red-cell T-activated patients after blood transfusion. The relationship between T antigen antibodies present in normal plasma and these reactions remains unclear. In this study, we assessed the haemolytic activity of T antibodies in vitro in comparison with anti-A/B antibodies. MATERIALS AND METHODS: We established a haemolysis assay based on treating target red-blood-cells (RBCs) with 2-aminoethylisothiouronium bromide (AET). Two hundred and seven blood donor sera were analysed for anti-T, anti-A/B haemolysins and anti-T agglutinins. RESULTS: Anti-T haemolysins were found in 4 (1·9%) blood donor sera using a standard haemolysis method and in 174 (84%) samples using AET-treated RBCs. Haemolysis correlated with agglutination titres (P<10(-7) ). With both methods, anti-T haemolysins were much weaker than anti-A and anti-B haemolysins. Gradual desialylation of RBCs showed a correlation between sialic acid level as indicated by agglutination with Sambucus nigra lectin and anti-T mediated haemolysis that was significantly increased (fold 2·4) independently of T antigen expression. CONCLUSION: These data indicate that, in vitro, anti-T-mediated haemolysis depends primarily on the degree of desialylation of target RBCs. They suggest that the haemolytic activity of T antibodies-containing human sera is usually weak and may only become significant in the very rare setting of a profound desialylation of RBCs.

Hour-specific bilirubin nomogram in infants with ABO incompatibility and direct Coombs-positive results.

OBJECTIVE: To determine the usefulness of the hour-specific Bhutani et al bilirubin nomogram when applied to infants with Coombs-positive test results. DESIGN: Retrospective chart review. SETTING: Term nursery and neonatal intensive care unit of a university-affiliated hospital. PATIENTS: All infants with A+ or B+ blood type born in our center from September 1, 2006, through August 31, 2008, to mothers with O+ blood. OUTCOMES: Proportion of infants with Coombs-positive results from the nomogram zones who required phototherapy and comparison of the percentage of infants with Coombs-positive results in each zone with the percentage of those with Coombs-negative results in each zone. RESULTS: A total of 240 infants with Coombs-positive and 460 with Coombs-negative results having a gestational age of 35 weeks or older were evaluated. Sensitivity and specificity of data for infants with direct Coombs-positive results in zone 4 (high risk; 74.2% and 97.1%) and those for infants in zones 3 (high-intermediate risk) and 4 combined (96.7% and 83.7%) compared favorably with the data from the Bhutani et al cohort, which had direct Coombs-negative results (54.0% and 96.2% for zone 4; 90.5% and 84.7% for zones 3 and 4 combined). The likelihood ratio for infants with direct Coombs-positive results in zone 4, 25.8 (95% confidence interval, 11.4-58.4), was twice that of the Bhutani et al cohort, 14.1 (11.0-18.1). The nomogram performed well in directing the timing of bilirubin level follow-up. All infants in zones 3 and 4 with Coombs-positive results were followed up after hospital discharge. None required an exchange transfusion or developed bilirubin encephalopathy. CONCLUSIONS: The Bhutani et al bilirubin nomogram reliably identified infants at gestational age of older than 35 weeks with direct Coombs-positive results who were at risk for significant hyperbilirubinemia and directed the timing of follow-up for these infants. This finding has direct clinical applicability to the health care professional practicing in the newborn nursery.

[What blood tests to predict severe hyperbilirubinemia in early maternity discharge?]. / Quel bilan sanguin réaliser avant une sortie précoce de maternité pour prédire un ictère sévère ?

OBJECTIVES: To evaluate the efficiency of blood tests (blood group, direct antiglobulin test) to assess severe hyperbilirubinemia in full-term newborns, delivered from mothers with rhesus negative or O group and to determine clinical and biological factors that may improve the prediction characteristics of this blood test. PATIENTS AND METHODS: We included all the full-term newborns, delivered from mothers with rhesus negative or O group, in a tertiary maternity ward, in 2005, from January6th to December31st. RESULTS: One thousand and ninety-two children were included. Newborns of A, B or AB group delivered from a mother 0 were at increased risk of presenting severe hyperbilirubinemia (OR=2.35 [1.22-4.52]). The negative predictive value was 96%. Yet, the determination of the Coombs test does not increase NPV. CONCLUSION: Systematic performance of blood test for newborns delivered from mother with O group does increase the ability to predict severe hyperbilirubinemia in a newborn infant. Direct antiglobulin test systematic performance remains questionable.

Cryopreserved autologous platelet transfusions in alloimmunized patients with acute leukemia.

Autologous platelets of 5 alloimmunized patients with acute leukemia in remission were cryopreserved with 5% dimethylsulfoxide in liquid nitrogen and retransfused in the following therapy-induced thrombocytopenic phase. The mean platelet recovery after freezing, thawing and washing was 85 +/- 6%. The mean corrected 1-hour increment in platelet counts was 11 (4-27) x 10(9)/l, i.e. 61% in comparison with fresh platelet transfusions in other patients. In vivo function of frozen platelets was documented by improvement of the posttransfusion bleeding time. Cryopreserved autologous platelets function hemostatically and can be used even for completely refractory patients and thus permit curative antileukemic therapy.

[Current validity of the exchange transfusion intervention by the classic indication. Our 15 years' experience]. / Validità attuale dell'intervento di exanguinotrasfusione secondo l'indicazione classica. Nostra esperienza di 15 anni.

In this paper the Authors report their personal experience of the use of exchange transfusion, secondary to classic indication, in the treatment of neonatal hyperbilirubinemia, in order to: 1) determine the trend over the past wears in the number of exchange transfused neonates, both from a global point of view and in relation to indications; 2) critically assess the risks, in terms of complications and mortality, correlated to exchange transfusion. Four hundred and eighty-eight neonates, who were subjected to 693 exchange transfusions in the Pediatric Clinic and Neonatal Division of the Policlinico Gemelli in Roma, were studied over a period of 15 years (1972-1986), according to the following indications: 214 cases of neonatal hyperbilirubinemia with MEN-Rh, 106 cases of neonatal hyperbilirubinemia with MEN-ABO and 168 cases of idiopathic hyperbilirubinemia. The total number of exchange transfused neonates decreased drastically from 304 in the period 1972-76 to 65 in the period 1982-86. The frequency of exchange transfused neonates because of idiopathic hyperbilirubinemia decreased significantly (p greater than 0.001), booth in comparison to the number of live births and in comparison to the number of exchange transfused neonates, probably due to the gradual introduction of phototherapy. The frequency of exchange transfused neonates with iso-Rh and iso-ABO decreased or remained stationary on account of the confirmed relative lesser efficacy of phototherapy on hemolytic jaundice. With regard to mortality and morbidity, 27 out of 488 neonates died during the neonatal period, but only 4 within six hours of exchange transfusion; the majority of those who died had a reduced gestational age and low birthweight, and were affected by a severe associated pathology.

Patients with anti-Vel--immunohematological characterization and transfusion management.

As reported by other authors we can confirm that the frequency of the blood group Vel negative in Lower Saxony is 1:4000. We report on a patient whose serological characteristics (IgM- and IgA-anti-Vel) made the transfusion of Vel positive blood impossible. Since it was not possible to obtain sufficient Vel negative red cell units in time, the patient was convinced to donate blood for autologous transfusions. This should be the procedure of first choice in the transfusion management of such patients.

[Efficacy of intensive blue double-lamp phototherapy in the treatment of ABO incompatibility and idiopathic severe hemolytic jaundice]. / Efficacia della fototerapia intensiva a doppia lampada blu nel trattamento degli itteri emolitici da incompatibilità ABO e idiopatici gravi.

Blue phototherapy is now generally accepted to be effective in the management of neonatal hyperbilirubinaemia. The response to phototherapy increases with increasing the skin surface area exposed to fluorescent illumination. We investigate the effects of "Intensive double direction phototherapy" (Double blue light 2 X 30 microW/cm2) in the treatment of neonatal hyperbilirubinaemia of 42 infants with ABO haemolytic diseases and "idiopathic" jaundice. We have found that serum bilirubin levels in newborn infants may be controlled more effectively with double light treatment and that the number of exchange transfusions was reduced.