RESUMO
BACKGROUND: Platelet transfusion refractoriness (PTR) secondary to human leukocyte antigen (HLA) alloimmunization is a challenge in the treatment of hematology-oncologypatients and increases the risk of morbidity and mortality from bleeding events. Guidelines for treating PTR have not been clearly described in literature. We aim to describe the practice patterns for the management of PTR secondary to HLA alloimmunization, and to assess the mortality, thrombosis and bleeding-related clinical outcomes at 30 days from diagnosis. METHODS: A retrospective review of 51 cases of PTR secondary to HLA alloimmunization were analyzed. RESULTS: The majority of patients (98 %) had a diagnosis of hematological malignancy of which 88.2 % were undergoing active chemotherapy. Clinically relevant bleeding, by ISTH criteria, was observed in 33.3 %; hemorrhagic shock was diagnosed in 7%. The rate of bleeding-related mortality was estimated at 7.8 %. The use of antifibrinolytics and plasma products (including intravenous immunoglobulin) was more common in cases with major versus non-major bleeding. Grade A or B1U HLA matched products were available in less than half of cases. CONCLUSIONS: There is heterogeneity in the management of the bleeding risk and bleeding events during PTR, with antifibrinolytics more commonly used in patients who suffered severe bleeding. Grade A and B1U HLA-matched platelets are not always readily available, and HLA-typing and HLA-antibody testing are not always performed prior to PTR. Prospective randomized control trials may help to determine the safety and efficacy of antifibrinolytics and other supportive measures in the management of PTR.
Assuntos
Plaquetas/imunologia , Isoanticorpos/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Institutos de Câncer , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto JovemAssuntos
ADP Ribose Transferases/genética , Códon sem Sentido , Proteínas de Membrana/genética , ADP Ribose Transferases/imunologia , Adolescente , Alelos , Tipagem e Reações Cruzadas Sanguíneas , DNA Complementar/genética , Feminino , Mutação da Fase de Leitura , Hemofilia A/complicações , Humanos , Isoanticorpos/sangue , Articulação do Joelho/cirurgia , Masculino , Proteínas de Membrana/imunologia , Pais , Fenótipo , Mutação Puntual , Deleção de Sequência , SíriaRESUMO
BACKGROUND: Alloimmunization can impact both the fetus and neonate. STUDY OBJECTIVES: (a) calculate the incidence of clinically significant RBC isoimmunization during pregnancy, (b) review maternal management and neonatal outcomes, (c) assess the value of prenatal and postnatal serological testing in predicting neonatal outcomes. STUDY DESIGN AND METHODS: A retrospective audit of consecutive alloimmunized pregnancies was conducted. Data collected included demographics, clinical outcomes, and laboratory results. Outcomes included: incidence of alloimmunization; outcomes for neonates with and without the cognate antigen; and sensitivity and specificity of antibody titration testing in predicting hemolytic disease of the fetus and newborn (HDFN). RESULTS: Over 6 years, 128 pregnant women (0.4%) were alloimmunized with 162 alloantibodies; anti-E was the most common alloantibody (51/162; 31%). Intrauterine transfusions (IUTs) were employed in 2 (3%) of 71 mothers of cognate antigen positive (CoAg+) neonates. Of 74 CoAg+ neonates, 58% required observation alone, 23% intensive phototherapy, 9% top up transfusion, and 3% exchange transfusion; no fetal or neonatal deaths occurred. HDFN was diagnosed in 28% (21/74) of neonates; anti-D was the most common cause. The sensitivity and specificity of the critical gel titer >32 in predicting HDFN were 76% and 75%, respectively (negative predictive value 95%; positive predictive value 36%). The sensitivity and specificity of a positive direct antiglobulin test (DAT) in predicting HDFN were 90% and 58%, respectively (NPV 97%; PPV 29%). CONCLUSION: Morbidity and mortality related to HDFN was low; most alloimmunized pregnancies needed minimal intervention. Titers of >32 by gel warrant additional monitoring during pregnancy.
Assuntos
Transfusão de Sangue Intrauterina , Eritroblastose Fetal , Transfusão de Eritrócitos , Transfusão Total , Isoanticorpos , Sistema do Grupo Sanguíneo Rh-Hr , Reação Transfusional , Adulto , Eritroblastose Fetal/sangue , Eritroblastose Fetal/imunologia , Eritroblastose Fetal/prevenção & controle , Feminino , Humanos , Recém-Nascido , Isoanticorpos/sangue , Isoanticorpos/imunologia , Masculino , Gravidez , Estudos Retrospectivos , Sistema do Grupo Sanguíneo Rh-Hr/sangue , Sistema do Grupo Sanguíneo Rh-Hr/imunologiaRESUMO
Introduction: Hemophilia A (HA) is an inherited bleeding disorder that, if not properly treated, is associated with debilitating joint damage due to recurrent hemarthroses as well as life-threatening bleeds including intracranial hemorrhage. For decades, the only method to prevent bleeding events was to infuse factor (F) VIII concentrates intravenously two to three times weekly. Although successful in reducing bleeding frequency, preventing a high proportion of joint disease, and extending life expectancy, standard continuous prophylaxis with FVIII is burdensome and insufficiently effective at preventing long-term joint dysfunction in some patients. In October 2018, the Federal Drug Administration approved a novel agent, emicizumab-kxwh, for the treatment of patients with HA without inhibitors. Areas covered: In this article, the preclinical and clinical development of emicizumab-kxwh will be reviewed. Data from licensure phase 3 clinical trials will be reviewed in detail discussing issues of both safety and efficacy. Expert opinion: As emicizumab-kxwh leads the way of a shift in treatment paradigm for patients with HA without inhibitors, a number of questions remain, including the impact of emicizumab-kxwh on joint and bone health, inhibitor development, and thrombotic risk. Ultimately, time and clinical investigation will be able to elucidate the influence of emicizumab-kxwh in these areas.
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Anticorpos Biespecíficos/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Hemofilia A/tratamento farmacológico , Animais , Anticorpos Biespecíficos/administração & dosagem , Anticorpos Biespecíficos/efeitos adversos , Anticorpos Biespecíficos/farmacocinética , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/farmacocinética , Antineoplásicos Imunológicos/administração & dosagem , Antineoplásicos Imunológicos/efeitos adversos , Antineoplásicos Imunológicos/farmacocinética , Inibidores dos Fatores de Coagulação Sanguínea/imunologia , Ensaios Clínicos como Assunto , Terapia Combinada , Avaliação Pré-Clínica de Medicamentos , Fator VIII/imunologia , Hemartrose/etiologia , Hemartrose/prevenção & controle , Hemartrose/terapia , Hemofilia A/complicações , Hemofilia A/imunologia , Hemorragia/etiologia , Hemorragia/prevenção & controle , Hemorragia/terapia , Humanos , Isoanticorpos/sangue , Isoanticorpos/imunologia , Resultado do TratamentoRESUMO
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.
Assuntos
Sistema ABO de Grupos Sanguíneos , Anemia Hemolítica Congênita , Incompatibilidade de Grupos Sanguíneos , Isoanticorpos , Reação Transfusional , Sistema ABO de Grupos Sanguíneos/sangue , Sistema ABO de Grupos Sanguíneos/imunologia , Anemia Hemolítica Congênita/sangue , Anemia Hemolítica Congênita/imunologia , Incompatibilidade de Grupos Sanguíneos/sangue , Incompatibilidade de Grupos Sanguíneos/imunologia , Feminino , Humanos , Recém-Nascido , Isoanticorpos/sangue , Isoanticorpos/imunologia , Masculino , Estudos Retrospectivos , Reação Transfusional/sangue , Reação Transfusional/imunologia , Reação Transfusional/prevenção & controleRESUMO
Purpose: Flotetuzumab (MGD006 or S80880) is a bispecific molecule that recognizes CD3 and CD123 membrane proteins, redirecting T cells to kill CD123-expressing cells for the treatment of acute myeloid leukemia. In this study, we developed a mathematical model to characterize MGD006 exposure-response relationships and to assess the impact of its immunogenicity in cynomolgus monkeys.Experimental Design: Thirty-two animals received multiple escalating doses (100-300-600-1,000 ng/kg/day) via intravenous infusion continuously 4 days a week. The model reflects sequential binding of MGD006 to CD3 and CD123 receptors. Formation of the MGD006/CD3 complex was connected to total T cells undergoing trafficking, whereas the formation of the trimolecular complex results in T-cell activation and clonal expansion. Activated T cells were used to drive the peripheral depletion of CD123-positive cells. Anti-drug antibody development was linked to MGD006 disposition as an elimination pathway. Model validation was tested by predicting the activity of MGD006 in eight monkeys receiving continuous 7-day infusions.Results: MGD006 disposition and total T-cell and CD123-positive cell profiles were well characterized. Anti-drug antibody development led to the suppression of T-cell trafficking but did not systematically abolish CD123-positive cell depletion. Target cell depletion could persist after drug elimination owing to the self-proliferation of activated T cells generated during the first cycles. The model was externally validated with the 7-day infusion dosing schedule.Conclusions: A translational model was developed for MGD006 that features T-cell activation and expansion as a key driver of pharmacologic activity and provides a mechanistic quantitative platform to inform dosing strategies in ongoing clinical studies. Clin Cancer Res; 24(11); 2631-41. ©2018 AACR.
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Anticorpos Biespecíficos/farmacocinética , Algoritmos , Animais , Anticorpos Biespecíficos/efeitos adversos , Anticorpos Biespecíficos/imunologia , Complexo CD3/antagonistas & inibidores , Complexo CD3/imunologia , Avaliação Pré-Clínica de Medicamentos , Feminino , Subunidade alfa de Receptor de Interleucina-3/antagonistas & inibidores , Subunidade alfa de Receptor de Interleucina-3/imunologia , Isoanticorpos/sangue , Isoanticorpos/imunologia , Macaca fascicularis , Masculino , Modelos Teóricos , Linfócitos T/imunologia , Linfócitos T/metabolismoRESUMO
BACKGROUND: Red blood cell (RBC) alloimmunization during pregnancy is still a major problem. Historically, anti-D antibodies are most likely to cause severe hemolysis, but other antibodies are also important. In Iceland, postnatal RhIg prophylaxis was implemented in 1969, universal RBC antibody screening was implemented in 1978, but antenatal RhIg prophylaxis is not yet routine. STUDY DESIGN AND METHODS: This nation-wide population study gathered data on alloimmunized pregnancies in Iceland between 1996 and 2015. Blood bank alloimmunization data were linked to Icelandic Medical Birth Registry data. RBC antibodies were classified as either clinically significant or clinically nonsignificant. RESULTS: In total, 912 positive antibody screens from 87,437 births were identified (1.04% prevalence). The most frequent antibodies were anti-M (19.4%), anti-E (19.0%), and anti-D (12.5%). Anti-D prevalence among D-negative mothers was 1.1%. Icelandic Medical Birth Registry data were available for 881 (96.6%) pregnancies. In the clinically significant group (n = 474), anti-E (27%) and anti-D (20%) were most common, whereas anti-M was most frequent (53%) in the clinically nonsignificant group (n = 407). Mothers in the clinically significant group were older, more often multigravidae, had more abortions and stillbirths, and had shorter gestational length. Newborns in the clinically significant group were less healthy, had lower weight and Apgar scores, and required more treatment. Among specificities in the clinically significant group, anti-D antibodies were most strongly associated with severe hemolysis. CONCLUSION: In this study, the prevalence of alloimmunization was similar to that in previous reports. Of all clinically significant antibodies, anti-D was most strongly associated with severe hemolysis, requiring phototherapy or exchange transfusions. Our data emphasize the importance of implementing an antenatal prophylactic RhIg program in Iceland in the near future.
Assuntos
Incompatibilidade de Grupos Sanguíneos/epidemiologia , Eritrócitos/imunologia , Complicações Hematológicas na Gravidez/sangue , Adulto , Incompatibilidade de Grupos Sanguíneos/imunologia , Coleta de Dados , Feminino , Hemólise , Humanos , Islândia , Isoanticorpos/sangue , Gravidez , Complicações Hematológicas na Gravidez/epidemiologia , Complicações Hematológicas na Gravidez/imunologia , Sistema de Registros , Imunoglobulina rho(D)/sangue , Adulto JovemRESUMO
Haemolytic disease of the foetus and newborn (HDFN) is caused by maternal red blood cells (RBC) alloimmunisation resulted from incompatibility of maternal and foetal RBCs. However, only a few HDFN attributed to anti-M were reported, varying from asymptomatic to severe anaemia with hydrops foetalis and even intrauterine death. A case of severe HDFN due to anti-M alloantibody from an alloimmunized grandmultiparous Malay woman with recurrent pregnancy loss is reported here. The newborn was delivered with severe and prolonged anaemia which required frequent RBC transfusions, intensive phototherapy and intravenous immunoglobulin administration. Although anti-M is rarely known to cause severe HDFN, a careful serological work-up and close assessment of foetal well-being is important, similar to the management of RhD HDFN. Alloimmunisation with anti-M type can lead to severe HDFN and even foetal loss.
Assuntos
Eritroblastose Fetal/sangue , Doenças Hematológicas/induzido quimicamente , Hidropisia Fetal/sangue , Isoanticorpos/efeitos adversos , Adulto , Eritroblastose Fetal/diagnóstico , Feminino , Desenvolvimento Fetal/imunologia , Feto/imunologia , Doenças Hematológicas/diagnóstico , Hemólise/imunologia , Humanos , Hidropisia Fetal/diagnóstico , Isoanticorpos/sangue , Malásia , GravidezRESUMO
BACKGROUND: Minor red blood cell antibodies are becoming a more common cause of hemolytic disease of the newborn. Anti-U are a rare alloantibody found almost exclusively in people of black descent. There is limited experience to guide the management of pregnancies complicated by anti-U. Furthermore, there is often no suitable cross-matched blood available for transfusion of a patient with anti-U. CASE REPORT: A 21-year-old P0G1 presented at 25 weeks' gestation with D- disease in pregnancy. She had a significant indirect antiglobulin test titer of 512. Anti-U were identified and no suitable cross-matched blood was available. Maternal blood was prepared for autologous intrauterine fetal transfusion. Two such transfusions were performed. RESULTS: A healthy fetus delivered at 32 weeks that did not require phototherapy or an exchange transfusion. CONCLUSION: Autologous transfusion of prepared maternal blood provides a safe option for intrauterine fetal therapy in pregnancies complicated by rare alloantibodies.
Assuntos
Transfusão de Sangue Intrauterina/métodos , Eritroblastose Fetal/terapia , Isoanticorpos/sangue , População Negra/genética , Eritroblastose Fetal/imunologia , Eritroblastose Fetal/prevenção & controle , Feminino , Idade Gestacional , Humanos , Gravidez , Transplante Autólogo , Adulto JovemAssuntos
Produtos Biológicos/imunologia , Produtos Biológicos/uso terapêutico , Proteínas/imunologia , Proteínas/uso terapêutico , Animais , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/imunologia , Anticorpos Monoclonais/uso terapêutico , Produtos Biológicos/efeitos adversos , Terapia Biológica/efeitos adversos , Terapia Biológica/métodos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Humanos , Isoanticorpos/sangue , Isoanticorpos/imunologia , Proteínas/efeitos adversos , Resultado do TratamentoRESUMO
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.
Assuntos
Sistema ABO de Grupos Sanguíneos/imunologia , Bancos de Sangue , Teste de Coombs , Eritroblastose Fetal/diagnóstico , Eritrócitos/imunologia , Isoanticorpos/sangue , Icterícia Neonatal/diagnóstico , Triagem Neonatal/métodos , Biomarcadores/sangue , Incompatibilidade de Grupos Sanguíneos/sangue , Incompatibilidade de Grupos Sanguíneos/diagnóstico , Incompatibilidade de Grupos Sanguíneos/imunologia , Transfusão de Sangue , Eritroblastose Fetal/sangue , Eritroblastose Fetal/imunologia , Eritroblastose Fetal/terapia , Sangue Fetal/imunologia , Teste de Histocompatibilidade , Humanos , Recém-Nascido , Icterícia Neonatal/sangue , Icterícia Neonatal/imunologia , Icterícia Neonatal/terapia , Fototerapia , Valor Preditivo dos Testes , Prognóstico , Fatores de TempoRESUMO
The frequency of red blood cell (RBC) alloimmunization in RhD positive pregnant women is not known in our population. We planned to determine its frequency and correlation with neonatal outcome. We included 1000 RhD positive pregnant women: 500 had 'normal pregnancy' (Group I) and another 500 had 'high risk pregnancy' (Group II). ABO and extended Rh phenotyping were done by tube technique, antibody screening and identification by gel technique. For alloimmunized women, the paternal and neonatal ABO and extended Rh typing were done. Neonatal direct antiglobulin test (DAT) was also done and their clinical outcome observed. The frequency of RBC alloimmunization was 0.7% (7/1000) and all these women were from group II (p = 0.015). The alloantibodies were anti-E (85.7%), anti-c (71.4%), anti-Cw (14.3%) and anti-S (14.3%). Also, 6 women had history of transfusion (p < 0.01). Of the 7 neonates born to alloimmunized mothers, 4 (57.14%) had a positive DAT. The mean duration of phototherapy was higher in the DAT positive neonates (p < 0.01) and 2 (50%) required exchange transfusion. Thus, the frequency of alloimmunization was 0.7% in RhD positive pregnant women. High risk pregnancies and antenatal patients having a history of blood transfusion should be considered for regular antibody screening.
Assuntos
Sistema ABO de Grupos Sanguíneos/sangue , Eritrócitos , Transfusão Feto-Materna/sangue , Transfusão Feto-Materna/epidemiologia , Isoanticorpos/sangue , Sistema do Grupo Sanguíneo Rh-Hr/sangue , Adulto , Feminino , Humanos , Recém-Nascido , Masculino , GravidezRESUMO
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.
Assuntos
Antígenos de Grupos Sanguíneos/imunologia , Incompatibilidade de Grupos Sanguíneos/diagnóstico , Transfusão de Sangue Autóloga , Glicoforinas/imunologia , Hidropisia Fetal/etiologia , Complicações na Gravidez/diagnóstico , Aborto Terapêutico , Adulto , Incompatibilidade de Grupos Sanguíneos/sangue , Tipagem e Reações Cruzadas Sanguíneas , Transfusão de Eritrócitos , Feminino , Glicoforinas/genética , Humanos , Isoanticorpos/sangue , Isoanticorpos/imunologia , Plasma , Gravidez , Complicações na Gravidez/imunologia , Complicações na Gravidez/terapiaRESUMO
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.
Assuntos
Eritroblastose Fetal/sangue , Eritroblastose Fetal/epidemiologia , Programas de Rastreamento/estatística & dados numéricos , Isoimunização Rh/sangue , Isoimunização Rh/epidemiologia , Sistema do Grupo Sanguíneo Rh-Hr/imunologia , Amniocentese/estatística & dados numéricos , Transfusão de Sangue/estatística & dados numéricos , Amostra da Vilosidade Coriônica/estatística & dados numéricos , Eritroblastose Fetal/diagnóstico , Eritroblastose Fetal/terapia , Feminino , Humanos , Incidência , Recém-Nascido , Isoanticorpos/sangue , Países Baixos/epidemiologia , Paridade , Gravidez , Terceiro Trimestre da Gravidez , Avaliação de Programas e Projetos de Saúde , Isoimunização Rh/diagnóstico , Isoimunização Rh/terapia , Fatores de Risco , Índice de Gravidade de Doença , Taxa de SobrevidaRESUMO
BACKGROUND: The therapeutic efficacy of red blood cell (RBC) transfusions in patients with autoimmune hemolytic anemia (AIHA) is highly debated because of speculations on the increased risk of transfusion reactions; yet it is a suggested adjuvant therapy in anemic patients with life-threatening hypoxemia. In this study, we evaluated the safety and efficacy of RBC transfusions in AIHA patients. METHODS: Daily changes in hemoglobin, total bilirubin, and lactate dehydrogenase (LDH) were assessed in 161 AIHA patients without bleeding history who were transfused once with 1-5 units of the least-incompatible RBCs and monitored over a seven-day period. Post-transfusion patients positive for alloantibodies only or those without RBC-specific antibodies were considered as control groups (N=100 for both groups). RESULTS: The three groups revealed similar increases in hemoglobin of 1.40-1.70 g/dL (autoantibodies), 1.20-1.60 g/dL (alloantibodies only), and 1.40-1.55 g/dL (no antibodies) for seven days following transfusion of 10 mL RBCs/kg. During follow-up, no significant changes in total bilirubin or LDH levels were detected in the AIHA group compared with controls. Influences due to autoantibody type, direct antiglobulin test (DAT) specificity and strength, and steroid therapy status on transfusion reactions were not evident in AIHA patients. In addition, changes in hemoglobin levels were significantly higher (P<0.001) in severe anemia (<5 g/dL) than in other patients. CONCLUSIONS: Transfusion of the least-incompatible RBCs in AIHA patients is effective and safe without any associated increase in hemolysis risk when compared with post-transfusion patients positive for alloantibodies or those lacking RBC-specific antibodies.
Assuntos
Anemia Hemolítica Autoimune/diagnóstico , Autoanticorpos/sangue , Transfusão de Eritrócitos , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Anemia Hemolítica Autoimune/terapia , Bilirrubina/sangue , Criança , Pré-Escolar , Feminino , Hemoglobinas/análise , Hemólise , Humanos , Hipóxia/terapia , Isoanticorpos/sangue , L-Lactato Desidrogenase/sangue , Masculino , Pessoa de Meia-Idade , Fatores Sexuais , Adulto JovemRESUMO
Bovine Neonatal Pancytopenia (BNP), a bleeding syndrome of neonatal calves, is caused by alloantibodies absorbed from the colostrum of particular cows. A commercial BVD vaccine is the likely source of alloantigens eliciting BNP associated alloantibodies. We hypothesized that the rare occurrence of BNP in calves born to vaccinated dams could be associated with genetic differences within dams and calves. We found that the development of BNP within calves was a heritable trait for dams, not for calves and had a high heritability of 19%. To elucidate which genes play a role in the development of BNP we sequenced candidate genes and characterized BNP alloantibodies. Alloantigens present in the vaccine have to be presented to the dam's immune system via MHC class II, however sequencing of DRB3 showed no differences in MHC class II haplotype between BNP and non-BNP dams. MHC class I, a highly polymorphic alloantigen, is an important target of BNP alloantibodies. Using a novel sequence based MHC class I typing method, we found no association of BNP with MHC class I haplotype distribution in dams or calves. Alloantibodies were detected in both vaccinated BNP and non-BNP dams and we found no differences in alloantibody characteristics between these groups, but alloantibody levels were significantly higher in BNP dams. We concluded that the development of BNP in calves is a heritable trait of the dam rather than the calf and genetic differences between BNP and non-BNP dams are likely due to genes controlling the quantitative alloantibody response following vaccination.
Assuntos
Doenças dos Bovinos/genética , Colostro/imunologia , Isoanticorpos/imunologia , Complexo Principal de Histocompatibilidade , Pancitopenia/veterinária , Animais , Animais Recém-Nascidos , Bovinos , Doenças dos Bovinos/imunologia , Feminino , Haplótipos , Isoanticorpos/sangue , Pancitopenia/genética , Pancitopenia/imunologia , Reação em Cadeia da Polimerase/veterinária , Vacinação/veterináriaRESUMO
We report a case of a hemolytic disease in a newborn from the first pregnancy due to anti-D antibodies. The maternal blood group was A Rhesus negative. She had an antibody screening test twice during the pregnancy (in the second trimester) and it was negative. The pregnancy was uneventful, without any invasive procedures and bleeding. The infant was born at 39 weeks of gestation in good overall condition. After the delivery the blood group of the neonate was indicated - A Rhesus positive, BOC positive. Anti-D antibodies were detected in maternal blood. Neonatal blood tests revealed severe anemia (hemoglobin level: 6.0g/dl, hematocrit: 22.2%, erythrocytes: 2.01T/L). During the first day of neonatal life, the newborn received two transfusions of red blood cells. Bilirubin level and rate of rise were not recommendation enough for exchange transfusion. The newborn was treated with continuous phototherapy since the delivery The perinatal period was complicated with intrauterine infection and respiratory failure. Hematopoietic vitamins and iron supplementation was initiated in the second week of neonatal life due to persistent anemia. The child remained under medical care of a hematologic clinic and received human recombinant erythropoietin treatment.
Assuntos
Anemia Neonatal/imunologia , Incompatibilidade de Grupos Sanguíneos/diagnóstico , Diagnóstico Tardio/efeitos adversos , Eritroblastose Fetal/diagnóstico , Eritroblastose Fetal/imunologia , Hematínicos/uso terapêutico , Isoanticorpos/sangue , Anticorpos/uso terapêutico , Incompatibilidade de Grupos Sanguíneos/imunologia , Transfusão de Sangue , Eritroblastose Fetal/sangue , Eritroblastose Fetal/terapia , Feminino , Humanos , Recém-Nascido , Ferro/uso terapêutico , Masculino , Fototerapia , Gravidez , Imunoglobulina rho(D)RESUMO
The Luminex technology has become an important tool for HLA antibody screening and identification. This is the most sensitive technology to detect HLA antibodies for transplant patients and patients on awaiting list, and it has ushered a new strategy to determine HLA compatibility between donor and recipient. Moreover, the clinical relevance of all detected anti-HLA antibodies is not well understood, because this technique was shown to be prone to many artefacts or interferences, leading to a complicated interpretation for biologists and clinicians. Our objective in this article is to provide a careful consideration about this solid phase assay, and to focus attention on raised questions about technical performance and interpretation of the results. We should keep in mind that our results could change the clinical management of sensitized patients, their aptitude to receive a graft, and their follow-up.
Assuntos
Antígenos HLA/imunologia , Teste de Histocompatibilidade/instrumentação , Teste de Histocompatibilidade/métodos , Isoanticorpos/sangue , Extração em Fase Sólida , Transfusão de Sangue Autóloga , Interpretação Estatística de Dados , Rejeição de Enxerto/diagnóstico , Rejeição de Enxerto/prevenção & controle , Teste de Histocompatibilidade/estatística & dados numéricos , Humanos , Testes Sorológicos/instrumentação , Testes Sorológicos/métodos , Extração em Fase Sólida/métodosRESUMO
BACKGROUND: The management of pregnant women with anti-Jsb is challenging due to the paucity of antigen-negative blood for fetal and neonatal transfusion. CASE REPORT: A 29-year-old woman with anti-Jsb was referred for assessment of recurrent fetal losses. With the presence of the sister as a historically matched donor, she was planned for active surveillance for fetal anemia during pregnancy. STUDY DESIGN AND METHODS: The fetus remained well until 21 weeks of gestation when signs of fetal anemia and early hydrops fetalis were noted. Anti-Jsb titer was at 128. The sister's red blood cells (RBCs) were cross-match incompatible. Urgent intrauterine transfusion (IUT) was performed with washed irradiated maternal RBCs, donated after cessation of heparin. The mother was given intravenous iron (IV-Fe) and continued on weekly recombinant human erythropoietin (rHu-EPO). RESULTS: Repeated IUTs were needed every 1 to 3 weeks. Throughout a 7-week period, three maternal donations were performed with total donated whole blood volume of 1250 mL, supporting four IUTs. At 29 weeks of gestation, the procedure was complicated by umbilical cord hematoma necessitating urgent cesarean section. A male newborn was delivered, transfused at birth, and subsequently treated with phototherapy and five top-up transfusions. CONCLUSION: This case represents a successful example of managing hemolytic disease of the fetus due to a rare antibody using maternal blood. It also supports previous data on safety of maternal donations during pregnancy and the use of combination of rHu-EPO and IV-Fe as a supportive measure.
Assuntos
Transfusão de Sangue Intrauterina/métodos , Eritroblastose Fetal/terapia , Isoanticorpos/efeitos adversos , Sistema do Grupo Sanguíneo de Kell/imunologia , Adulto , Doadores de Sangue , Eritroblastose Fetal/etiologia , Feminino , Humanos , Recém-Nascido , Isoanticorpos/sangue , Masculino , Mães , Gravidez , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
BACKGROUND: Neonates with Rhesus c (Rh c) hemolytic disease of the fetus and newborn (HDFN) are often managed in the same way as neonates with Rhesus D (Rh D) HDFN, although evidence to support this policy is limited. The objective of this study was to evaluate neonatal outcome in severe Rh c HDFN compared to Rh D HDFN. STUDY DESIGN AND METHODS: A retrospective study of (near-)term neonates with severe Rh c (n = 22) and Rh D HDFN (n = 103; without additional antibodies) admitted to the Leiden University Medical Center between January 2000 and October 2011 was conducted. The need for intrauterine transfusions (IUTs), phototherapy, exchange transfusions (ETs), and top-up transfusions up to 3 months of age were recorded and compared between both groups. RESULTS: Although there was a trend for a slightly more severe antenatal course for Rh D HDFN reflected by an earlier need for and higher number of IUTs (median [interquartile range], 2 [1.5-4] vs. 2 [1-2] in Rh c HDFN; p = 0.070), no significant differences were found for the postnatal course between Rh c and Rh D group in days of phototherapy (mean, Days 4.8 and 4.6, respectively; p = 0.569), need for ET (50% vs. 44%, respectively; p = 0.589), and top-up transfusions (62% vs. 78%, respectively; p = 0.128). CONCLUSION: Postnatal outcome in neonates with severe Rh c HDFN is similar compared to neonates with severe Rh D hemolytic disease in terms of days of phototherapy, need for ET, and need for top-up transfusions. These results justify a similar postnatal management of neonates with Rh D and Rh c HDFN.