Can RH+ whole blood be safely used as an alternative to RH- product? An analysis of efforts to improve the sustainability of a hospital's low titer group O whole blood program.

BACKGROUND: Low-titer group O whole blood (LTO-WB) has recently gained popularity in trauma centers for the acute resuscitation of hemorrhagic shock. However, limited supplies of Rh- product prevent implementation and strain sustainability at many trauma centers. We set out to identify whether Rh+ LTO-WB could be safely substituted for RH- product, regardless of patient's Rh status. METHODS: Following Institutional Review Board approval, information on all trauma patients receiving prehospital or emergency department transfusion of uncrossed, emergency release LTO-WB (11/17-10/19) were evaluated. Patients were first divided into those who received Rh- versus Rh+ product, the assessed by Rh of the recipient. Serial hemolysis panels, transfusion reactions, and outcomes were compared. RESULTS: Six hundred thirty-seven consecutive trauma patients received emergency release LTO-WB. Of these, 448 received Rh+ product, while 189 received Rh- LTO-WB. Patients receiving Rh+ product were more likely to be men (81 vs. 70%) and have lower field blood pressure (median 99 vs. 109) and GCS (median 7 vs. 12); all p < 0.05. There were no differences in blood product volume, hemolysis laboratories, transfusion reactions, complications, or survival. We then separated patients by Rh status (577 were Rh+, 70 were Rh-). Rh- patients were older (median age 54 vs. 39), more likely to be women (57 vs. 26%), and more likely to have sustained blunt trauma than their Rh+ counterparts (92 vs. 70%); all p < 0.05. There were no differences in hemolysis laboratories, transfusion reactions, complications, or survival between Rh+ and Rh- patients, regardless of Rh product received. CONCLUSION: When Rh- whole blood is unavailable or in short supply, Rh+ LTO-WB appears to be a safe alternative for the resuscitation of hemorrhagic shock in both Rh+ and Rh- patients. Use of Rh+ product may help trauma centers incorporate LTO-WB into their hospital and improve sustainability of such programs. LEVEL OF EVIDENCE: Therapeutic, Level III.

Targeted antenatal anti-D prophylaxis for RhD-negative pregnant women: a systematic review.

BACKGROUND: All non-sensitized Rhesus D (RhD)-negative pregnant women in Germany receive antenatal anti-D prophylaxis without knowledge of fetal RhD status. Non-invasive prenatal testing (NIPT) of cell-free fetal DNA in maternal plasma could avoid unnecessary anti-D administration. In this paper, we systematically reviewed the evidence on the benefit of NIPT for fetal RhD status in RhD-negative pregnant women. METHODS: We systematically searched several bibliographic databases, trial registries, and other sources (up to October 2019) for controlled intervention studies investigating NIPT for fetal RhD versus conventional anti-D prophylaxis. The focus was on the impact on fetal and maternal morbidity. We primarily considered direct evidence (from randomized controlled trials) or if unavailable, linked evidence (from diagnostic accuracy studies and from controlled intervention studies investigating the administration or withholding of anti-D prophylaxis). The results of diagnostic accuracy studies were pooled in bivariate meta-analyses. RESULTS: Neither direct evidence nor sufficient data for linked evidence were identified. Meta-analysis of data from about 60,000 participants showed high sensitivity (99.9%; 95% CI [99.5%; 100%] and specificity (99.2%; 95% CI [98.5%; 99.5%]). CONCLUSIONS: NIPT for fetal RhD status is equivalent to conventional serologic testing using the newborn's blood. Studies investigating patient-relevant outcomes are still lacking.

Cancer type predicts alloimmunization following RhD-incompatible RBC transfusions.

BACKGROUND: Immunosuppressed, RhD-negative oncology patients tend to have lower rates of sensitization to the D antigen when they receive transfusion with RhD-positive blood components. Clinical factors associated with alloimmunization to the D antigen in RhD-negative oncology patients when they receive transfusion with RhD-positive red blood cells (RBCs) have not been well defined. STUDY DESIGN AND METHODS: This was a 4-year, retrospective analysis identifying RhD-negative oncology patients who received RhD-positive RBCs and were not previously alloimmunized to the D antigen. Age, sex, race, ABO group, primary oncology diagnosis, and numbers of RhD-incompatible RBC transfusions were recorded. The association between antibody formation and clinical factors was studied. The incidence of alloanti-D was calculated from a subsequent antibody-detection test performed at least 28 days after receipt of the first transfusion of RhD-positive RBCs. RESULTS: In total, 545 RhD-negative oncology patients received 4295 RhD-positive RBC transfusions. Of these, 76 (14%) became alloimmunized to the D antigen. Diagnosis type was the only factor significantly associated with responder status. The logistic regression model indicated that patients who had myelodysplastic syndrome or solid malignancies were more likely to be responders than those who had acute leukemia. CONCLUSION: We measured a 14% sensitization rate to the D antigen in our RhD-negative oncology population. The rate of alloimmunization was higher in patients who had solid cancers (22.6%) or myelodysplastic syndrome (23%) compared with those who had other hematologic malignancies (7%). Knowledge of diagnoses that predispose to RhD alloimmunization enables better utilization of RhD-negative RBCs during times of shortage.

Third trimester screening for alloimmunisation in Rhc-negative pregnant women: evaluation of the Dutch national screening programme.

OBJECTIVE: To evaluate the effect of red blood cell (RBC) antibody screening in the 27th week of pregnancy in Rhc-negative women, on detection of alloimmunisation, undetected at first trimester screening ('late' alloimmunisation), and subsequent haemolytic disease of the fetus and newborn (HDFN), to assess risk factors for late alloimmunisation. DESIGN: Prospective cohort and nested case-control study. SETTING: The Netherlands. POPULATION: Two-year nationwide cohort. METHODS: Prospective inclusion of Rhc-negative women with negative first trimester screening and of screen-negative controls. Assessment of incidence and numbers needed to screen (NNS) of late alloimmunisation and HDFN; logistic regression analysis to establish risk factors for late alloimmunisation. MAIN OUTCOME MEASURES: Late alloimmunisation, HDFN. RESULTS: Late alloimmunisation occurred in 99 of 62 096 (0.159%) Rhc-negative women; 90% had c/E antibodies and 10% non-Rhesus antibodies. Severe HDFN (fetal/neonatal transfusion) occurred in two of 62 096 (0.003%) of Rhc-negative women and 2% of late alloimmunisations; moderate HDFN (phototherapy) occurred in 20 children [22.5%; 95% confidence interval (CI), 13.8-31.1%]. Perinatal survival was 100%. The NNS to detect one HDFN case was 2823 (31 048 for severe, 3105 for moderate HDFN). Significant risk factors were former blood transfusion [odds ratio (OR), 10.4; 95% CI, 1.14-94.9], parity (P-1: OR, 11.8; 95% CI, 3.00-46.5; P > 1: OR, 7.77; 95% CI, 1.70-35.4) and amniocentesis/chorionic villus sampling during current pregnancy (OR, 9.20; 95% CI, 1.16-72.9). CONCLUSIONS: Additional screening of Rhc-negative women improved the detection of late alloimmunisation and HDFN, facilitating timely treatment, with a NNS of 2823. Independent risk factors for late alloimmunisation were blood transfusion, parity and chorionic villus sampling/amniocentesis in the current pregnancy. The occurrence of most factors before the current pregnancy suggests a secondary immune response explaining most late alloimmunisations. TWEETABLE ABSTRACT: Third trimester screening for alloimmunisation in Rhc-neg women improves detection and treatment of severe HDFN.

El antígeno Diego alcanza los 60 años de edad: su descubrimiento y desarrollo / Diego antigen reach 60 years old: discovery and development

El antigeno Diego fue descubierto en junio de 1953 por el hematólogo estadounidense Philip Levine (1900-1987) en una muestra de sangre enviada desde Venezuela por el pediatra Miguel Raga Mendoza (1917-1986). El propósitus, de nombre Diego, había fallecido a los 3 días de edad por causa de una enfermedad hemolítica del recién nacido. Levine bautizó al nuevo antigeno con el nombre de diego y lo clasificó como un factor privado o familiar de baja prevalencia. En 1955, los hematólogos Miguel Layrisse (1919-2002) y Tulio Arents (1918-1990), y el obstetra Rafael Dominguez Sisco (1908-1980) llegaron a la conclusión de que el antígeno Diego tenía una mayor frecuencia que la reportada por Levine y que por tanto constituía un grupo sanguíneo de alta prevalencia en poblaciones indigenas venezolanas. Estos resultados fueron extendidos a otras poblaciones indígenas de América, demostrandose también su existencia en personas de origen asiático (mongoloides) y su ausencia en las razas caucasoide y negroide. El antígeno Diego se transformó así en el primer marcador mongoloide de gran valor antropológico, genético y clínico. En la década de 1990 se demostró que el antígeno Diego estaba asociado con la proteína eritrocitaria denominada banda 3; esta funciona como un intercambiador de aniones (AE-1) que se expresa también en células del túbulo renal. Actualmente, el grupo snguíneo Diego está formado por 22 antígenos o alelos.

On June 1953, the American hematologist Philip Levine (1900-1987) discovered a new erythrocyte antigen in the blood of a sick child collected in Venezuela by the pediatrician Miguel Raga Mendoza (1917-1986). The propositus, named Diego, was affected by a hemolytic disease of the newborn and died 3 days after delivery. Levine named the antigen Diego (Diª) and classified it as a private or familial factor of low prevalence. In 1955, the hematologists Miguel Layrisse (1919-2002) and Tulio Arends (1918-1990), and the obstetrician Rafael Dominguez Sisco (1908-1980) concluded that the Diego antigen had a greater frecuency than that reported by Levine, constituting a blood group of high prevalence in Venezuelan aboriginal populations. Similar results were obtained in other aboriginal populations of the American continent. The Diego antigen was also present in high frequency in people of asiatic origin (mongoloids), and absent in caucasoid and negroid people. Thus, the Diego antigen became the first mongoloid marker of great anthropological, genetic and clinical importance. In 1992, the Diego antigen was found associated with the erythrocyte protein named band 3, later known to function as an anion exchanger (AE-1). Band 3 is also expressed on cells of the renal tubules. Presenthy, the Diego blood group is formed by 22 antigens or allelles.

Anti-Rh(c), "little c," isoimmunization: the role of rHuEpo in preventing late anemia.

The overall prevalence of non-Rh-D isoimmunization seems to lie between 0.15% and 1.1%. Anti-Rh(c) alloimmunization, "little c," occurs in 0.07% of pregnancies and shows a quite broad clinical presentation. Late anemia is a frequent problem occurring in the setting of isoimmunization. It occurs more frequently after intrauterine blood transfusions or exsanguinotransfusion, and it can be thought as a hyporegenerative anemia. The authors describe the use of human recombinant erythropoietin in preventing late anemia in a case of anti-Rh(c) isoimmunization. The use of human recombinant erythropoietin is a valid tool for preventing late-onset anemia due to either anti-Rh-D or non-anti-Rh-D isoimmunization.

Genotipagem RhD fetal não invasiva no acompanhamento de gestantes RhD negativo / Non invasive Fetal RHD Genotyping in management of pregnant RhD negative women

O acompanhamento de gestantes de fenótipo RhD negativo é baseado na premissa de que seus fetos podem estar em risco de desenvolver a doença hemolítica perinatal (DHPN) ou eritroblastose fetal, trazendo sérios riscos ao feto em decorrência de hemólise, com consequente anemia, hidropsia e, por vezes, óbito intrauterino. Procedimentos invasivos como amniocentese ou cordocentese podem ser utilizados para se inferir o fenótipo RhD fetal, entretanto, oferecem riscos ao feto e à gestante. Nos últimos anos, o conhecimento sobre a genética dos grupos sanguíneos e o desenvolvimento de técnicas de biologia molecular tem permitido a inferência de fenótipos de grupos sanguíneos a partir da detecção do material genômico. Inicialmente, a genotipagem do DNA fetal para o gene RhD era feita a partir de amostras de amniócitos ou de vilosidades coriônicas. No entanto, por tratar-se de testes invasivos, traziam risco ao feto e à gestante. A possibilidade de se obter DNA fetal a partir do plasma materno foi um grande avanço na prática clínica, por ser um procedimento não invasivo e, portanto, isento de risco. Esta revisão apresenta os princípios da técnica e os resultados de diferentes protocolos para genotipagem RhD fetal (publicados ao longo dos anos) e qual o seu propósito no acompanhamento das gestantes RhD negativo

The RhD negative pregnant women management has been based on the fact that their fetuses may be at risk of developing hemolytic diseases (DHPN) or erythroblastosis fetalis. This condition may bring serious risks to the fetus due to hemolysis, with consequent anemia and hydrops and sometimes, intrauterine death. Invasive procedures such as amniocentesis or cordocentesis may be performed to assess the fetal RhD phenotype, however, it offers risks to both fetus and pregnant woman. In recent years, the knowledge about the genetics of blood groups and the development of molecular biology techniques has allowed the inference of blood group phenotypes by the detection of genomic material. Initially, the fetal DNA genotyping for the RHD gene was performed from amniocytes or chorionic villi samples. Unfortunately, these invasive tests could bring risk to the fetus and the pregnant woman. However, the possibility of obtaining fetal DNA from maternal plasma has been a major advance in clinical practice, as being a non-invasive procedure and therefore not providing any risks. This review presents the principles of techniques and results of different protocols for fetal RHD genotyping (published over the years) and its goal on the management of RhD negative pregnant women

A new fetal RHD genotyping test: costs and benefits of mass testing to target antenatal anti-D prophylaxis in England and Wales.

BACKGROUND: Postnatal and antenatal anti-D prophylaxis have dramatically reduced maternal sensitisations and cases of rhesus disease in babies born to women with RhD negative blood group. Recent scientific advances mean that non-invasive prenatal diagnosis (NIPD), based on the presence of cell-free fetal DNA in maternal plasma, could be used to target prophylaxis on "at risk" pregnancies where the fetus is RhD positive. This paper provides the first assessment of cost-effectiveness of NIPD-targeted prophylaxis compared to current policies. METHODS: We conducted an economic analysis of NIPD implementation in England and Wales. Two scenarios were considered. Scenario 1 assumed that NIPD will be only used to target antenatal prophylaxis with serology tests continuing to direct post-delivery prophylaxis. In Scenario 2, NIPD would also displace postnatal serology testing if an RhD negative fetus was identified. Costs were estimated from the provider's perspective for both scenarios together with a threshold royalty fee per test. Incremental costs were compared with clinical implications. RESULTS: The basic cost of an NIPD in-house test is £16.25 per sample (excluding royalty fee). The two-dose antenatal prophylaxis policy recommended by NICE is estimated to cost the NHS £3.37 million each year. The estimated threshold royalty fee is £2.18 and £8.83 for Scenarios 1 and 2 respectively. At a £2.00 royalty fee, mass NIPD testing would produce no saving for Scenario 1 and £507,154 per annum for Scenario 2. Incremental cost-effectiveness analysis indicates that, at a test sensitivity of 99.7% and this royalty fee, NIPD testing in Scenario 2 will generate one additional sensitisation for every £9,190 saved. If a single-dose prophylaxis policy were implemented nationally, as recently recommended by NICE, Scenario 2 savings would fall. CONCLUSIONS: Currently, NIPD testing to target anti-D prophylaxis is unlikely to be sufficiently cost-effective to warrant its large scale introduction in England and Wales. Only minor savings are calculated and, balanced against this, the predicted increase in maternal sensitisations may be unacceptably high. Reliability of NIPD assays still needs to be demonstrated rigorously in different ethnic minority populations. First trimester testing is unlikely to alter this picture significantly although other emerging technologies may.

An elevated fetal interleukin-6 concentration can be observed in fetuses with anemia due to Rh alloimmunization: implications for the understanding of the fetal inflammatory response syndrome.

OBJECTIVE: The fetal inflammatory response syndrome (FIRS) has been described in the context of preterm labor and preterm prelabor rupture of the membranes and is often associated with intra-amniotic infection/inflammation. This syndrome is characterized by systemic fetal inflammation and operationally defined by an elevated fetal plasma interleukin (IL)-6. The objective of this study was to determine if FIRS can be found in fetuses with activation of their immune system, such as the one observed in Rh alloimmune-mediated fetal anemia. METHODS: Fetal blood sampling was performed in sensitized Rh-D negative women with suspected fetal anemia (n=16). Fetal anemia was diagnosed according to reference range nomograms established for the assessment of fetal hematologic parameters. An elevated fetal plasma IL-6 concentration was defined using a cutoff of >11 pg/ml. Concentrations of IL-6 were determined by immunoassay. Non-parametric statistics were used for analysis. RESULTS: (1) The prevalence of an elevated fetal plasma IL-6 was 25% (4/16); (2) there was an inverse relationship between the fetal hematocrit and IL-6 concentration -- the lower the hematocrit, the higher the fetal IL-6 (r=-0.68, p=0.004); (3) fetuses with anemia had a significantly higher plasma IL-6 concentration than those without anemia (3.74 pg/ml, interquartile range (IQR) 1.18-2.63 vs. 1.46 pg/ml, IQR 1.76-14.7; p=0.02); (4) interestingly, all fetuses with an elevated plasma IL-6 concentration had anemia (prevalence 40%, 4/10), while in the group without anemia, none had an elevated fetal plasma IL-6. CONCLUSIONS: An elevation in fetal plasma IL-6 can be observed in a subset of fetuses with anemia due to Rh alloimmunization. This observation suggests that the hallmark of FIRS can be caused by non-infection-related insults. Further studies are required to determine whether the prognosis of FIRS caused by intra-amniotic infection/inflammation is different from that induced by alloimmunization.

Molecular RH blood group typing of serologically D-/CE+ donors: the use of a polymerase chain reaction-sequence-specific primer test kit with pooled samples.

The known presence of RHD blood group alleles in apparently D­ individuals who are positive for C or E antigens leads to an appropriate investigation for the RHD gene on the red blood cells (RBCs) of D­ blood donors, thus preventing their RBCs from immunizing D­ recipients. Ready-to-use polymerase chain reaction­sequence-specific primer (PCR-SSP) typing kits are available and allow single-sample results. The need to perform this testing on a large number of donors affiliated with the Transfusion Department of Udine (Northern Italy) led to the use of molecular genetic RH blood group typing with PCR-SSP test kits and DNA samples mixed in pools. From a population of 35,000 blood donors screened for D antigen by serologic typing, a total of 235 samples, distributed in pools of 5 DNA samples, were investigated. Positive results were reevaluated by opening the pools and retesting single samples. Validation of DNA-pool typing with commercial kits was done. Among 235 genotyped samples, 12 were found to be PCR positive (5.1%), exhibiting DEL genotype and RHD-CE-D hybrid alleles. Our data demonstrate that the use of a PCR-SSP commercial test kit with pooled samples is a helpful and valid method to correctly detect RHD alleles. As a consequence, we reclassified our donors as carriers of potentially immunogenic alleles.

Risk factors for the presence of non-rhesus D red blood cell antibodies in pregnancy.

OBJECTIVE: To identify risk factors for the presence of non-rhesus D (RhD) red blood cell (RBC) antibodies in pregnancy. To generate evidence for subgroup RBC antibody screening and for primary prevention by extended matching of transfusions in women <45 years. DESIGN: Case-control study. SETTING: Nationwide evaluation of screening programme for non-RhD RBC antibodies. CASES: consecutive pregnancies (n=900) with non-RhD immunisation identified from 1 September 2002 to 1 June 2003 and 1 October 2003 to 1 July 2004; controls (n=968): matched for obstetric caregiver and gestational age. METHODS: Data collection from the medical records and/or from the respondents by a structured phone interview. MAIN OUTCOME MEASURES: Significant risk factors for non-RhD immunisation in multivariate analysis. RESULTS: Significant independent risk factors: history of RBC transfusion (OR 16.7; 95% CI: 11.4-24.6), parity (para-1 versus para-0: OR 1.3; 95% CI: 1.0-1.7; para-2 versus para-0: OR 1.4; 95% CI: 1.0-2.0; para >2 versus para-0: OR 3.2; 95% CI: 1.8-5.8), haematological disease (OR 2.1; 95% CI: 1.0-4.2), history of major surgery (OR 1.4; 95% CI: 1.1-1.8). For the clinically most important antibodies, anti-K, anti-c and other Rh-nonD-antibodies RBC transfusion was the most important risk factor, especially for anti-K (OR 96.4; 95%-CI: 56.6-164.1); 83% of the K-sensitised women had a history of RBC transfusion. Pregnancy-related risk factors were a prior male child (OR 1.7; 95% CI: 1.2-2.3) and caesarean section (OR 1.7; 95% CI: 1.1-2.7). CONCLUSIONS: RBC transfusion is by far the most important independent risk factor for non-RhD immunisation in pregnancy, followed by parity, major surgery and haematological disease. Pregnancy-related risk factors are a prior male child and caesarean section. Subgroup screening for RBC antibodies, with exclusion of RhD-positive para-0 without clinical risk factors, is to be considered. This approach will be equally sensitive in detecting severe Haemolytic Disease of the Fetus and Newborn compared with the present RBC antibody screening programme without preselection. Primary prevention by extending preventive matching of transfusions in women younger than 45 will prevent more than 50% of pregnancy immunisations.

Bilirubin/albumin ratios in fetal blood and in amniotic fluid in rhesus immunization.

OBJECTIVE: To test the hypothesis that unconjugated bilirubin is equally distributed over the albumin molecules present in fetal blood and amniotic fluid in Rhesus (Rh) immunization. METHODS: Molar concentrations of unconjugated bilirubin and albumin were measured in fetal blood and amniotic fluid samples, obtained before the first intrauterine transfusion in 30 nonhydropic, anti-D-alloimmunized fetuses, with gestational ages ranging from 20 to 35 weeks. RESULTS: Bilirubin concentration in amniotic fluid was best predicted by a combination of bilirubin concentration in fetal blood (P<.001), albumin concentration in fetal blood (P=.008), and albumin concentration in amniotic fluid (P<.001) (adjusted R2=0.91). The bilirubin/albumin ratios in fetal blood were linearly correlated with the bilirubin/albumin ratios in amniotic fluid (R2=0.75, P<.001). However, the bilirubin/albumin ratios in fetal blood were always higher than the bilirubin/albumin ratios in amniotic fluid (regression coefficient 1.4, 95% confidence interval 1.1-1.7). In our population, a bilirubin/albumin ratio in amniotic fluid of 0.10 or greater had a better sensitivity and specificity to predict severe anemia (Z hemoglobin -5 standard deviations or less) than the Queenan 4 or the Liley 2c line. CONCLUSION: The relation between fetal hemolysis and amniotic fluid bilirubin concentration is based on the linear correlation between bilirubin/albumin ratios in fetal blood and in amniotic fluid. The slope in Queenan's and Liley's chart follows that of the albumin concentration in amniotic fluid during gestation. LEVEL OF EVIDENCE: III.

[Obtention of a heterohybridoma for production of type IgM monoclonal antibodies against the D antigen of the Rh system]. / Obtención de heterohibridoma productor de anticuerpos monoclonales de tipo IgM contra el antígeno D del sistema Rh.

The objective was to obtain a heterohybridoma capable of producing a monoclonal antibody with IgM type anti-D specificity (Rh system), that could be used as a reactive for hemoclasification. Mononuclear cells (MNC) were extracted from a blood sample of a highly sensitized woman, five days after giving birth to an Rh positive child. These were then transformed with the culture supernatant (CSN) of B05.8 cells, rich in Epstein Barr virus (EBV). Once transformed and in exponential growth, they were fused with K6H6/B5 line cells using PEG 4.000 as a fusing agent in a 1:1 proportion. After fusion, they were seeded in culture plates in order to evaluate the formation of hybrids and the secretion of specific antibodies in the CSN of each well. The efficiency of the fusion was 1.8 x 10(-6), making it possible to obtain an anti-D IgM producing clone, which we named BMS-9. This clone could be maintained in constant culture for three months, producing antibodies in a concentration of 4 microg/mL in de CSN. It was also possible to obtain antibodies with an Artificial Capilar System (ACS) reaching a concentration of 24 microg/mL. Potency was determined using Ror cells. In CSN at immediate centrifugation (IC): 1 x 32, score 52; 15' from incubation at room temperature (RT): 1 x 1,024 score 105. With that ACS product at IC: 1 x 32 score 54; 15' from incubation at RT: 1 x 8.192 score 136; and a 37 degrees C: 1 x 8,192 score 136. Reactivity was detected with red cells D(IIIa), D(IV), D(Va), D(VI) type IV, D(VII), DFR, DNU, STEM+, DAR and DAU. There was no reactivity with red cells D(IIIc), DI(Va), D(V) type II, D(VI) types I, II y III, Ro(HAR), DOL and weak D type II. During field study, no false negative or false positive reactions were detected. A stable heterohybridoma was obtained, producer of IgM type anti-D, with enough qualities to be used in blood typing. Given the excellent qualities of the antibody, we are evaluating dilution media and the addition of type IgG antibodies in order to manufacture a reactive for use in hemoclassification.

Reliability of second trimester triple screening for Down syndrome in rhesus-negative women.

OBJECTIVE: To find out whether there is considerable influence on second trimester serum concentrations owing to the rhesus status. STUDY DESIGN: This retrospective cohort study was performed at the Perinatology Unit of the GATA Haydarpasa Teaching Hospital. During the study interval, 2265 pregnancies met inclusion criteria. The blood samples were collected in 117 pregnancies with a maternal rhesus-negative blood group status. The control group consisted of 2148 pregnancies with a maternal rhesus-positive blood group status. Statistical analysis was performed by SPSS 11.0 statistical software. RESULTS: Pregnancies with a maternal rhesus-negative blood group status were identified in 117 patients. The overall prevalence of pregnancies with a maternal rhesus-negative blood group status were 5.1% in our study. Only unconjugated estriol multiples of the median values were significantly decreased in rhesus-negative women (P<0.001). Alpha-fetoprotein and human chorionic gonadotrophin multiples of the median values did not differ significantly (P>0.05). CONCLUSION: We conclude that if second trimester screening test to be used in Rh negative pregnancies, either the corrected value should be referred or double test result should be considered ignoring the unconjugated estriol result. Another option is the first trimester Down syndrome screening test.

O desfecho perinatal da aloimunização eritrocitária não-relacionada ao antígeno Rhd / The outcome of perinatsl erythrocyte alloimmunization unrelated to the RhD antigen

Analisar o desfecho perinatal da aloimunização eritrocitária não-relacionada ao antígeno RhD. De forma complementar, confrontar os resultados perinatais com os da aloimunização RhD e com aqueles de gestantes Rh-não-sensibilizadas...

Aloinmunizacion a un antigeno del sistema rh de alta frecuencia / Alloimmunization to a high frequency Rh antigen

Describimos el caso de una embarazada sensibilizada con un aloanticuerpo anti-Rh17 de muy amplia reactividad. Los glóbulos rojos de la paciente presentaban una deleción parcial de los antígenos del sistema Rh, responsable de la aloinmunización encontrada. Debido a la dificultad de obtener sangre compatible se elaboró un plan de transfusión autóloga para cubrir las posibles demandas. El análisis molecular del locus RH demostró la presencia de un alelo híbrido RHCE-D(5-7)-CE que generaba el fenotipo delecionado.

Avaliar a correlação entre a concentração da hemoglobina e a medida ecográfica do diâmetro biventricular externo em fetos anêmicos de gestantes isoimunizadas / Assessment of the correlation between hemoglobin concentration and the echographic measurement of biventricular outer diameter in anemic fetuses of isoimmunized women

OBJETIVO: Verificar se existe correlação significativa entre a medida ecográfica do diâmetro biventricular externo e a concentração sérica da hemoglobina fetal pré-transfusional e se essa medida ecográfica poderá vir a ser utilizada como marcador não invasivo da anemia fetal. MÉTODOS: Estudo transversal prospectivo, no qual foram selecionadas 65 cordocenteses realizadas em 36 fetos anêmicos de mães portadoras de isoimunização pelo fator Rh. Obteve-se a medida do diâmetro biventricular externo (DBVE), por meio do modo M, utilizando-se aparelho de ultra-som convencional. Anterior à transfusão foi obtida amostra de 0,5ml de sangue fetal, para dosagem da hemoglobina, sendo a medida imediatamente realizada através de espectrofotometria, no equipamento Hemocue®. Como análise estatística foi utilizada a regressão dos mínimos quadrados, aceitando-se p<0,05 e análise multivariada. RESULTADOS: Foram observadas correlação inversa entre a concentração da hemoglobina no sangue fetal no momento prévio à transfusão e a medida do DBVE e correlação direta entre a medida do DBVE e a idade gestacional, e, também, através da análise multivariada que, à medida que a concentração de hemoglobina fetal cai, o DBVE aumenta, independentemente da influência da idade gestacional nesse parâmetro. CONCLUSAO: Existe correlação inversa entre a concentração da hemoglobina no sangue fetal e a medida do DBVE, independente da idade gestacional. Os achados sugerem que o DBVE poderá vir a ser um marcador ecográfico de predição do nível de hemoglobina de fetos de gestantes isoimunizadas.

Hyporegenerative anemia associated with Rh hemolytic disease: treatment failure of recombinant erythropoietin.

A postnatal hyporegenerative anemia may complicate Rh hemolytic disease. Intramedullary hemolysis, bone marrow suppression, and erythropoietin deficiency have been implicated etiologically. Treatment with recombinant erythropoietin (r-EPO) has yielded encouraging preliminary results. The authors describe an infant with Rh isoimmunization who developed severe hyporegenerative anemia unresponsive to a 5-week course of r-EPO. Two additional doses at 12 weeks resulted in brisk reticulocytosis, coinciding with a 16-fold decline in the anti-Rh(D) antibody titer. Thus, treatment with r-EPO may be ineffective when anti-Rh(D) antibody titers are high. The authors also show that erythropoietin deficiency in hyporegenerative anemia is not as frequent and severe as originally thought.