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1.
Transfus Apher Sci ; 63(2): 103871, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38245405

RESUMO

The histo-blood group antigens P, P1 and Pk are a closely related set of glycosphingolipid structures expressed by red blood cells and other tissues. None of these three characters is expressed on p cells, a null phenotype that arises in the context of homozygous mutation of the A4GALT gene. Subjects with p phenotype spontaneously develop a natural alloantibody named anti-PP1Pk, which is a mixture of IgG and IgM against P1, P and Pk. While anti-P1 is a weak cold antibody with poor clinical significance, anti-P and anti-Pk antibodies are potent haemolysins responsible for severe hemolytic transfusion reactions. The rare anti-PP1Pk alloantibodies are associated with recurrent spontaneous abortion in the first trimester of gestation. P and Pk antigens are expressed at high levels on the placenta and antibodies directed against both these structures are deleterious to placental trophoblasts. Here we describe the use of plasma exchange (PEX) in a nulliparous 39-year-old woman with anti-PP1Pk antibodies and a history of repeated spontaneous early abortions and hypofertility. The patient underwent apheresis starting from the third week throughout the pregnancy and a healthy child was delivered by cesarean section at 35 WG. The newborn required only phototherapy within a few days of life. We can state that an early treatment with the only PEX has proven to be effective and safe in the management of a fetomaternal P-incompatibility caused by a high anti-PP1Pk titer (256).


Assuntos
Aborto Habitual , Anemia Hemolítica Autoimune , Antígenos de Grupos Sanguíneos , Adulto , Feminino , Humanos , Recém-Nascido , Gravidez , Aborto Habitual/etiologia , Aborto Habitual/terapia , Anemia Hemolítica Autoimune/terapia , Cesárea/efeitos adversos , Isoanticorpos , Sistema do Grupo Sanguíneo P/genética , Placenta , Troca Plasmática/efeitos adversos , Gestantes
2.
Haematologica ; 108(10): 2639-2651, 2023 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-37078267

RESUMO

Although red blood cell (RBC) transfusions save lives, some patients develop clinically-significant alloantibodies against donor blood group antigens, which then have adverse effects in multiple clinical settings. Few effective measures exist to prevent RBC alloimmunization and/or eliminate alloantibodies in sensitized patients. Donor-related factors may influence alloimmunization; thus, there is an unmet clinical need to identify which RBC units are immunogenic. Repeat volunteer blood donors and donors on iron supplements have elevated reticulocyte counts compared to healthy non-donors. Early reticulocytes retain mitochondria and other components, which may act as danger signals in immune responses. Herein, we tested whether reticulocytes in donor RBC units could enhance RBC alloimmunization. Using a murine model, we demonstrate that transfusing donor RBC units with increased reticulocyte frequencies dose-dependently increased RBC alloimmunization rates and alloantibody levels. Transfusing reticulocyte-rich RBC units was associated with increased RBC clearance from the circulation and a robust proinflammatory cytokine response. As compared to previously reported post-transfusion RBC consumption patterns, erythrophagocytosis from reticulocyte-rich units was increasingly performed by splenic B cells. These data suggest that reticulocytes in a donated RBC unit impact the quality of blood transfused, are targeted to a distinct compartment, and may be an underappreciated risk factor for RBC alloimmunization.


Assuntos
Isoanticorpos , Reticulócitos , Humanos , Camundongos , Animais , Doadores de Sangue , Eritrócitos , Fatores de Risco
3.
Clin Lab ; 69(4)2023 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-37057931

RESUMO

BACKGROUND: Anti-s is a rare alloantibody, and the reported cases of hemolytic disease of the fetus and newborn (HDFN) caused by anti-s are limited to non-Asian populations. METHODS: Here, we report the case of a Chinese woman with a history of multiple pregnancies who developed an alloantibody with anti-s specificity. RESULTS: Her newborn developed HDFN caused by anti-s but the clinical symptoms were not serious. After supportive treatment and bilirubin light phototherapy, the baby was discharged with a good prognosis. CONCLUSIONS: This is the first reported case of anti-s-induced HDFN in a Chinese patient, highlighting the need for further research in the Asian population.


Assuntos
Antígenos de Grupos Sanguíneos , População do Leste Asiático , Eritroblastose Fetal , Isoanticorpos , Feminino , Humanos , Recém-Nascido , Gravidez , Eritroblastose Fetal/diagnóstico , Eritroblastose Fetal/etiologia , Eritroblastose Fetal/imunologia , Eritroblastose Fetal/terapia , Feto/imunologia , Hemólise/imunologia , Isoanticorpos/imunologia , Antígenos de Grupos Sanguíneos/imunologia , Fototerapia
4.
HLA ; 102(2): 147-156, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36961354

RESUMO

Spherotech (SPT) microparticles capture non-specific binding materials present in test serum, and EDTA removes the so called" prozone effect". This study presents a novel approach of combined SPT-EDTA serum treatment prior to Luminex HLA antibody testing to remove high background, and prozone effect in a single step process, and compared the efficacy of SPT-EDTA serum pre-treatment with AdsorbOut (ADS) and Serum Cleaner (SC) to reduce background in solid phase immunoassays (SPI). A total of 21 serum samples with a history of elevated negative control (NC) values ≥500, and 20 samples with normal NC values were included to assess the potential adverse effects. A problem of high background was noted in 25% of our samples in SPI. We observed 80% effectiveness in reducing NC values <500 with SPT-EDTA serum pre-treatment compared to 72%, and 67% for ADS and SC-treated sera, respectively. Interestingly, we found a strong correlation in antibody-binding levels between SPT versus ADS; and ADS versus SC-treated sera for both phenotype and single antigen bead assays (p < 0.001). No adverse effect was noted on NC, positive control (PC) values, PC/NC ratios in the upfront use of SPT-EDTA as compared to EDTA alone. Our data revealed that combined SPT-EDTA treated sera is more effective than ADS, and SC in reducing high background in SPI. Taken together, SPT-EDTA serum treatment prior to Luminex HLA Ab testing is cost-effective, our laboratory saves nearly 30% of the annual total cost for Ab testing and improved test turnaround time by two business days.


Assuntos
Anticorpos , Soro , Ácido Edético , Alelos , Imunoensaio , Teste de Histocompatibilidade , Isoanticorpos
5.
Transfus Clin Biol ; 30(1): 5-7, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35944885

RESUMO

Red blood cell (RBC) alloimmunization which is the production of antibodies in response to foreign red cell antigen(s) may occur through exposure to cells or tissues from a genetically different member of same species via transfusion, transplantation or pregnancy. It may cause hemolytic disease of fetus and newborn (HDFN). Usually the incidence of HDFN due to irregular erythrocyte antibody is rare in primigravida. Here we report a primigravida pregnant woman who developed multiple alloantibodies and the neonate developed severe HDFN. A 36-year-old primigravida pregnant woman who had no history of significant medical issues except surgery done for severe endometriosis 1 year back and she had no history of previous blood transfusion presented to us for delivery. The antibody screening came out to be positive with a reaction in cell I and cell II of the antibody screening panel. Further, a mixture of anti D + anti C + anti E alloantibodies were identified using 16 cells panel, select cells and red cell phenotyping. The neonate developed severe HDFN which was managed with phototherapy, exchange transfusion and IvIg. There was no exposure history for sensitization except bleeding in early 2nd trimester. There was a significant discrepancy among mother, father and neonate Rh phenotype which was resolved with clinical history of Invitro fertilization (IVF) with sperm donation. This index case illustrates the need of antibody screening in primigravida antenatal women specially for Rh D negative high risk cases. It also shows importance of Rh Kell typing in sperm donors for future transfusion support of the child.


Assuntos
Anemia Hemolítica Autoimune , Eritroblastose Fetal , Feminino , Masculino , Gravidez , Humanos , Isoanticorpos , Sêmen , Eritroblastose Fetal/etiologia , Eritroblastose Fetal/terapia , Eritrócitos , Transfusão de Sangue , Anemia Hemolítica Autoimune/complicações
6.
Transfus Apher Sci ; 61(6): 103458, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35623958

RESUMO

BACKGROUND: "Asia type" DEL red blood cells (RBCs) express a very weak D antigen and cannot be detected by routine RhD typing. Thus, it is routinely typed as D-negative (D-) blood group and transfused to D- recipients. Here we described a case of secondary alloanti-D immunization that was associated with transfusion of DEL RBCs to D- recipients and was initially considered as primary alloanti-D immunization. CASE PRESENTATION: A 44-year-old D- woman (G2P2) with adenomyosis and anemia underwent transabdominal hysterectomy. She received four units of D- RBCs before operation. Before transfusion, the alloantibody screening test was negative. Four days after the first transfusion, she needed another RBC transfusion. Unexpectedly, the routine pre-transfusion alloantibody screening test became positive and anti-D (titer, 128-fold) was identified, indicating an alloanti-D immunization. The anti-D developed four days after the first transfusion was unexplained, so alloantibody identification was performed on the sample collected before the first transfusion, and weak anti-D combined with anti-E, which was not detectable during the previous routine pre-transfusion alloantibody screening test with non-enzyme-treated screening cells, was identified using bromelain-treated panel cells. The remaining blood samples of first transfusion in bag tails from two donors were collected for RHD genotyping analysis. One donor was later identified as "Asia type" DEL having RHD* 1227 A/01 N.01 genotype. CONCLUSION: Caution should be applied when we conclude that transfusion of "Asia type" DEL RBCs to true D- recipients could induce primary alloanti-D immunization, especially if the short time interval between transfusion and detection of anti-D is observed.


Assuntos
Doadores de Sangue , Sistema do Grupo Sanguíneo Rh-Hr , Feminino , Humanos , Adulto , Sistema do Grupo Sanguíneo Rh-Hr/genética , Eritrócitos , Isoanticorpos , Imunização
7.
Rev Assoc Med Bras (1992) ; 68(5): 670-674, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35584494

RESUMO

OBJECTIVE: To assess the prevalence of maternal alloantibodies in pregnant women at a maternity hospital in northeastern Brazil and describe their perinatal outcomes. METHODS: A retrospective cohort study reviewed maternal and newborn medical records between January 2017 and October 2018 to assess for the presence of maternal alloantibodies. RESULTS: The following maternal alloantibodies were found in the 41 cases surveyed: anti-D, 28 cases (45%); anti-C, 7 cases (11%); anti-c, 1 case (1.6%); anti-E, 4 cases (6.4%); anti-Cw, 1 case (1.6%); anti-K, 2 cases (3.2%); anti-Jka, 1 case (1.6%); anti-M, 3 cases (4.8%); anti-Fya, 2 cases (3.2%); anti-Fyb, 1 case (1.6%); anti-Lea, 5 cases (8%); anti-Leb, 3 cases (4.8%); and anti-Dia, 4 cases (6.4%). Anti-D antibodies were the most frequent cause of erythrocyte alloimmunization (80%). Fetal anemia was observed in four pregnancies based on the peak systolic velocity of the middle cerebral artery. In one case, the mother showed anti-M, and anti-Lea alloimmunization, but the direct antiglobulin test results for the newborn were negative, and no unfavorable neonatal outcomes were observed. In one case of a mother with anti-C and anti-D alloimmunization, the neonate showed anti-D antibodies only in the serological panel and required phototherapy. Neonates with plasma antibodies and jaundice requiring phototherapy only had a serological panel with anti-D, anti-C, anti-c, and anti-E antibodies. Intervention was required for 2.5% of pregnant women with positive antibody screens and 81% of newborns with positive direct antiglobulin test results. CONCLUSION: Despite being a rare condition, maternal alloimmunization by irregular antibodies can result in high perinatal morbidity and mortality.


Assuntos
Antígenos de Grupos Sanguíneos , Isoanticorpos , Brasil/epidemiologia , Feminino , Hospitais , Humanos , Recém-Nascido , Gravidez , Estudos Retrospectivos
8.
Acta Obstet Gynecol Scand ; 100(12): 2216-2225, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34476807

RESUMO

INTRODUCTION: Anti-D alloimmunization is the most common cause of severe hemolytic disease of the fetus and newborn (HDFN). The management of pregnancies affected by less frequent red blood cell (RBC) antibodies poses a challenge to clinicians, and perinatal outcomes are less well described. This study aimed to describe the frequency of clinically significant RBC antibodies in our pregnant population and analyze the risk of prenatal and postnatal treatment for HDFN in relation to our national risk classification system and management guidelines. MATERIAL AND METHODS: A retrospective cohort study in the population of all alloimmunized singleton pregnancies in the Stockholm region 1990-2016. Descriptive summaries of different RBC antibodies and pregnancy outcomes were presented, the risks of intrauterine blood transfusion (IUT) and neonatal treatment for HDFN were estimated by type of antibodies. RESULTS: Of the 1724 alloimmunized pregnancies, 1079 (63%) were at risk of HDFN and constituted our study cohort. Anti-D was detected in 492 (46%) pregnancies, followed by anti-E in 161 (15%), and anti-c in 128 (12%). Eighty-seven (8%) pregnancies had IUT, with the highest risk in pregnancies affected by anti-D combined with other antibodies. The maximum titer recorded before IUT was 64 or above, except for two pregnancies affected by anti-c, for which the maximum titers were 8 and 16. For the 942 (95%) live-born neonates from 992 alloimmunized pregnancies without IUT, the median gestational age at birth was 38+5  weeks compared with 35+5  weeks for those who had IUT. Neonatal treatment was most common in the anti-D alone and anti-D combined groups, with 136 (57%) and 21 (44%), respectively, treated with phototherapy and 35 (15%) and 9 (20%) receiving exchange transfusions, respectively. For pregnancies complicated by moderate- and low-risk antibodies, phototherapy was less frequent (32 [36%] and 21 [19%]) and exchange transfusion was rare (5 [6%] and 3 [3%]). CONCLUSIONS: Anti-D, especially in combination with other antibodies, presents the highest risk of severe HDFN. The classification of less frequent and less well-known RBC antibodies into risk groups can help clinicians in assessing the risk of HDFN and counseling alloimmunized pregnant women regarding the risk of prenatal and postnatal treatments.


Assuntos
Eritroblastose Fetal/diagnóstico , Eritrócitos/imunologia , Cuidado Pré-Natal , Transfusão de Sangue Intrauterina , Estudos de Coortes , Eritroblastose Fetal/terapia , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Isoanticorpos , Gravidez , Estudos Retrospectivos
9.
Immunohematology ; 37(1): 13-17, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33962487

RESUMO

Many patients with anti-Yta receive multiple transfusions of Yt(a+) red blood cells (RBCs) with no ill effects. However, anti-Yta has been implicated in hemolytic transfusion reactions. Antibody identification typically determines specificity of antibodies and their clinical significance to justify blood requirements for antigen-negative blood when clinically significant antibodies are involved. Occasionally, specificity of antibody is of variable significance. Variability in clinical significance is a characteristic of anti-Yta that may affect the clinical management of such patients. This case reports the outcome of an incompatible transfusion in an 83-year-old female patient with anti-Yta, -D, -C, -Leab, and -HI who was admitted to the hospital for a severe urinary tract hemorrhage and fever. The patient was transfused with 1 crossmatch-incompatible group A, Yt(a+), D-, C-, E-, S- RBC unit in an emergency medical event. During that time, the patient exhibited chills, shivering, and tachycardia. Decreases in hemoglobin and hematocrit were noted. Laboratory parameters for hemolysis, such as total bilirubin, direct bilirubin, and lactate dehydrogenase, were increased. Based on clinical and laboratory evaluation, it was concluded that the patient had an acute hemolytic transfusion reaction caused by anti-Yta. The patient was successfully treated with antipyretics, antihistamines, and corticosteroids. Urinary tract hemorrhaging was stopped. Anemia was additionally improved with parenteral iron supplementation, and further transfusion was not required. Immunohematology 2021;37:13-17.Many patients with anti-Yta receive multiple transfusions of Yt(a+) red blood cells (RBCs) with no ill effects. However, anti-Yta has been implicated in hemolytic transfusion reactions. Antibody identification typically determines specificity of antibodies and their clinical significance to justify blood requirements for antigen-negative blood when clinically significant antibodies are involved. Occasionally, specificity of antibody is of variable significance. Variability in clinical significance is a characteristic of anti-Yta that may affect the clinical management of such patients. This case reports the outcome of an incompatible transfusion in an 83-year-old female patient with anti-Yta, -D, -C, -Leab, and -HI who was admitted to the hospital for a severe urinary tract hemorrhage and fever. The patient was transfused with 1 crossmatch-incompatible group A, Yt(a+), D­, C­, E­, S­ RBC unit in an emergency medical event. During that time, the patient exhibited chills, shivering, and tachycardia. Decreases in hemoglobin and hematocrit were noted. Laboratory parameters for hemolysis, such as total bilirubin, direct bilirubin, and lactate dehydrogenase, were increased. Based on clinical and laboratory evaluation, it was concluded that the patient had an acute hemolytic transfusion reaction caused by anti-Yta. The patient was successfully treated with antipyretics, antihistamines, and corticosteroids. Urinary tract hemorrhaging was stopped. Anemia was additionally improved with parenteral iron supplementation, and further transfusion was not required. Immunohematology 2021;37:13­17.


Assuntos
Isoanticorpos , Reação Transfusional , Idoso de 80 Anos ou mais , Incompatibilidade de Grupos Sanguíneos , Tipagem e Reações Cruzadas Sanguíneas , Feminino , Hemólise , Humanos
10.
Transfus Apher Sci ; 60(3): 103096, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33612449

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 Jovem
13.
Transfusion ; 60(11): 2537-2546, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32893897

RESUMO

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/imunologia
14.
Hum Antibodies ; 28(3): 245-252, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32417769

RESUMO

A case report of a 38 years old ABO group A and Rhesus D negative multiparous, gravidae 8 and para 2, Nigerian woman who had a case of premarital miscarriage and who was not offered anti-D prophylaxis as part of her management. Lady went on to develop alloantibody D and Jka. Lady has had 7 further pregnancies post the miscarriage. The first child who is B Rhesus D positive is the only surviving child. The surviving child was delivered severely jaundiced and needed management post-delivery for haemolytic disease of the foetus and newborn (HDFN). Lady has had a history of a stillbirth. She was given a non-clinically indicated anti-D prophylaxis during the second pregnancy despite having been previously sensitized. The second baby died 3 months after delivery from complications of HDFN. She had had a further history of 5 miscarriages. She has had challenge with conception since 2010. Alloantibody testing confirms the presence alloantibody D and anti-Jka. Finding from this is a clear case of sub-optimal laboratory, obstetric and neonatal care offered particularly to pregnant women who are Rh D negative and those with alloantibodies in Nigeria. The Nigerian government will need to implement evidenced-based best practices; determination of alloantibody status of pregnant women during their first antenatal visit; provision of facilities for alloantibody identification, titration, quantification and feto maternal haemorrhage testing (FMH); implementation of a policy on universal access to anti-D prophylaxis for pregnant Rh D negative women who are not previously sensitized; provision of facilities required for the optimal intrauterine management of HDFN (foetal genotype testing, intrauterine transfusion, doppler ultrasound to diagnose anaemia inutero and provision of donor blood that meet the minimum requirements for intrauterine transfusion); determination of Rh D status of women who require a termination of pregnancy and provision of prophylactic anti-D for those found Rh D negative within 72 hours of procedure and the optimization of the knowledge of Medical Laboratory Scientist, Obstetricians, Neonatologist, Pharmacist and Traditional Birth Attendants in a bid to reduce the residual number of women who become sensitized and the number of preventable deaths of babies with HDFN.


Assuntos
Aborto Espontâneo , Eritroblastose Fetal , Adulto , Criança , Feminino , Feto , Humanos , Recém-Nascido , Isoanticorpos , Nigéria , Gravidez
15.
Front Immunol ; 11: 476, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32265927

RESUMO

Replacement therapy with coagulation factor VIII (FVIII) represents the current clinical treatment for patients affected by hemophilia A (HA). This treatment while effective is, however, hampered by the formation of antibodies which inhibit the activity of infused FVIII in up to 30% of treated patients. Immune tolerance induction (ITI) protocols, which envisage frequent infusions of high doses of FVIII to confront this side effect, dramatically increase the already high costs associated to a patient's therapy and are not always effective in all treated patients. Therefore, there are clear unmet needs that must be addressed in order to improve the outcome of these treatments for HA patients. Taking advantage of preclinical mouse models of hemophilia, several strategies have been proposed in recent years to prevent inhibitor formation and eradicate the pre-existing immunity to FVIII inhibitor positive patients. Herein, we will review some of the most promising strategies developed to avoid and eradicate inhibitors, including the use of immunomodulatory drugs or molecules, oral or transplacental delivery as well as cell and gene therapy approaches. The goal is to improve and potentiate the current ITI protocols and eventually make them obsolete.


Assuntos
Fator VIII/imunologia , Hemofilia A/tratamento farmacológico , Tolerância Imunológica/efeitos dos fármacos , Fatores Imunológicos/uso terapêutico , Isoanticorpos/imunologia , Transferência Adotiva , Animais , Anticorpos Biespecíficos/farmacologia , Anticorpos Biespecíficos/uso terapêutico , Anticorpos Monoclonais Humanizados/farmacologia , Anticorpos Monoclonais Humanizados/uso terapêutico , Portadores de Fármacos , Composição de Medicamentos , Avaliação Pré-Clínica de Medicamentos , Fator IXa/imunologia , Fator VIII/administração & dosagem , Fator VIII/uso terapêutico , Fator X/imunologia , Feminino , Terapias Fetais , Terapia Genética , Hemofilia A/imunologia , Hemofilia A/terapia , Humanos , Fragmentos Fc das Imunoglobulinas/administração & dosagem , Imunoterapia Adotiva , Isoanticorpos/biossíntese , Tecido Linfoide/imunologia , Camundongos , Modelos Animais , Células Vegetais , Gravidez , Proteínas Recombinantes de Fusão/administração & dosagem , Proteínas Recombinantes de Fusão/uso terapêutico , Linfócitos T Reguladores/transplante
16.
Vox Sang ; 115(4): 334-338, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32080868

RESUMO

BACKGROUND AND OBJECTIVES: D-negative patients are at risk of developing an alloantibody to D (anti-D) if exposed to D during transfusion. The presence of anti-D can lead to haemolytic transfusion reactions and haemolytic disease of the newborn. Anti-D alloimmunization can also complicate allogeneic haematopoietic stem cell transplantation (HSCT) with haemolysis and increased transfusion requirements. The goal of this study was to determine whether cancer centres have transfusion practices intended to prevent anti-D alloimmunization with special attention in patients considered for HSCT. METHODS AND MATERIALS: To understand transfusion practices regarding D-positive platelets in D-negative patients with large transfusion needs, we surveyed the 28 cancer centres that are members of the National Comprehensive Cancer Network® (NCCN® ). RESULTS: Nineteen centres responded (68%). Most centres (79%) avoid transfusing D-positive platelets to RhD-negative patients when possible. Four centres (21%) avoid D-positive platelets only in D-negative women of childbearing age. If a D-negative patient receives a D-positive platelet transfusion, 53% of centres would consider treating with Rh immune globulin (RhIg) to prevent alloimmunization in women of childbearing age. Only one centre also gives RhIg to all D-negative patients who are HSCT candidates including adult men and women of no childbearing age. CONCLUSION: There is wide variation in platelet transfusion practices for supporting D-negative patients. The majority of centres do not have D-positive platelet transfusion policies focused on preventing anti-D alloimmunization specifically in patients undergoing HSCT. Multicentre, longitudinal studies are needed to understand the clinical implications of anti-D alloimmunization in HSCT patients.


Assuntos
Transfusão de Plaquetas/efeitos adversos , Isoimunização Rh/prevenção & controle , Imunoglobulina rho(D)/imunologia , Reação Transfusional/prevenção & controle , Adulto , Segurança do Sangue/métodos , Feminino , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Recém-Nascido , Isoanticorpos/imunologia , Masculino , Pessoa de Meia-Idade , Serviço Hospitalar de Oncologia/estatística & dados numéricos , Isoimunização Rh/etiologia , Isoimunização Rh/imunologia , Imunoglobulina rho(D)/uso terapêutico , Inquéritos e Questionários , Reação Transfusional/etiologia , Reação Transfusional/imunologia
17.
J Ethnopharmacol ; 253: 112682, 2020 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-32087318

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Huangkuisiwufang (HKSWF) is composed of Abelmoschus manihot (L.) Medik., Astragalus mongholicus, Polygonum cuspidatum, Curcuma longa L. Abelmoschus Manihot (L.) Medik. has been widely used for the treatment of chronic renal disease, oral ulcers and burn in China for centuries (Committee of the Pharmacopoeia of PR China, 2010). Abelmoschus manihot (L.) Medik., Polygonum cuspidatum, Curcuma longa L. have been mainly applied in folk medicine for their therapeutic effects on diabetes, cancer, heart disease and other diseases. AIM OF THE STUDY: We aimed to investigate the renoprotective function of HKSWF in anti-Thy nephritis model and clarify the relevant mechanisms. MATERIALS AND METHODS: One week after the model of glomerulonephritis created by injecting anti-thymocyte serum (ATS), rats were treated with Huangkui capsule, enalapril or HKSWF by gavage for a period of 8 weeks. The therapeutic effect was evaluated by detection of proteinuria, plasma creatine, blood urea nitrogen (BUN), podocyte injury, glomerular accumulation of extracellular matrix (ECM) and the markers of oxidative stress and renal fibrosis. RNA Sequencing (RNA-seq), KEGG and western blotting analysis were performed to indicate the signaling pathway involved in the therapeutic effect of HKSWF. RESULTS: Nephritic rats presented the increase of BUN, serum creatinine (Scr), proteinuria, podocyte damage, glomerular fibrosis, Ang II type 1 receptor (AT1R), and the reduction of creatinine clearance (Ccr). In contrast, application of HKSWF to nephritic rats decreased the levels of BUN and proteinuria, promoted mesangial cell recovery and improved oxidative stress level and podocyte injury. KEGG analysis revealed that pyruvate metabolism was the most significantly upregulated pathway in rats treated with HKSWF compared to disease control group. Increased pyruvate dehydrogenase and PAI-1 caused by nephritis was inhibited by HKSWF interposition. Furthermore, dichloroacetate sodium (DCA), an agonist of pyruvate dehydrogenase, could stimulate PAI-1 expression, which was suppressed by HKSWF. CONCLUSION: Chinese herbal preparation HKSWF has remarkable curative effects on glomerulonephritis animals. HKSWF attenuates pyruvate dehydrogenase to improve glomerular injury.


Assuntos
Nefrite/tratamento farmacológico , Substâncias Protetoras/uso terapêutico , Complexo Piruvato Desidrogenase/antagonistas & inibidores , Animais , Células Cultivadas , Isoanticorpos , Glomérulos Renais/efeitos dos fármacos , Glomérulos Renais/patologia , Masculino , Células Mesangiais/efeitos dos fármacos , Camundongos , Nefrite/patologia , Estresse Oxidativo/efeitos dos fármacos , Compostos Fitoquímicos/análise , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/uso terapêutico , Substâncias Protetoras/química , Substâncias Protetoras/farmacologia , Ratos Sprague-Dawley
18.
Tidsskr Nor Laegeforen ; 140(1)2020 01 14.
Artigo em Inglês, Norueguês | MEDLINE | ID: mdl-31948214

RESUMO

BACKGROUND: Individuals with the K0 phenotype are extremely rare. They may develop anti-Ku antibodies, which react with all antigens of the Kell blood group system, thereby leading to haemolytic transfusion reactions and haemolytic disease of the fetus and newborn. CASE PRESENTATION: A primigravida who was transfused with one unit of red blood cells due to iron deficiency anaemia developed anti-Ku antibodies. The pregnancy was closely monitored by ultrasound and antibody titres. Maternal autologous blood collection was performed twice during the last trimester as back-up in case of maternal peripartum bleeding, and a few frozen K0 red blood cell units were provided in case of severe fetal anaemia. At gestational week 36+6, labour was induced due to increasing antibody titres and high blood velocities in the fetal middle cerebral artery during systole. The woman was delivered vaginally without need for transfusion. The infant was diagnosed with haemolytic disease of the fetus and newborn and treated with phototherapy, repeated infusions of intravenous immunoglobulin and iron supplements until normalisation of haemoglobin at three months of age. INTERPRETATION: Iron deficiency anaemia should be treated primarily with iron supplementation before considering blood transfusions, which pose the risk of developing alloantibodies that can cause transfusion complications and haemolytic disease of the fetus and newborn.


Assuntos
Eritroblastose Fetal , Reação Transfusional , Transfusão de Sangue , Eritroblastose Fetal/etiologia , Eritroblastose Fetal/terapia , Feminino , Humanos , Recém-Nascido , Isoanticorpos , Sistema do Grupo Sanguíneo de Kell , Gravidez
19.
Transfus Apher Sci ; 59(1): 102602, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31303507

RESUMO

Anti-G is commonly present with anti-D and anti-C and can confuse serological investigations. The differentiation of anti-G from anti-D and anti-C is particularly essential for the accurate diagnosis of hemolytic disease of the fetus and newborn (HDFN) and appropriate administration of anti-D immunoglobulin prophylaxis in Rhesus (Rh) negative women. We reported a rare case of anti-G together with anti-D and anti-C in a pregnant woman and her female neonate. The titers of IgG anti-D, anti-C, and anti-G in the woman were 256, 128, and 32, respectively. While the titers of IgG anti-D, anti-C, and anti-G in the neonate were 16, 8, and 4, respectively. The neonate experienced mild HDFN and only received phototherapy during hospitalization. This report discusses the diagnostic strategy and clinical significance of differentiating anti-G from anti-D and anti-C.


Assuntos
Eritroblastose Fetal/diagnóstico , Isoanticorpos/imunologia , Sistema do Grupo Sanguíneo Rh-Hr/imunologia , Adulto , Eritroblastose Fetal/patologia , Eritroblastose Fetal/terapia , Feminino , Humanos , Recém-Nascido
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