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1.
Scand J Immunol ; 92(1): e12890, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32299122

RESUMO

Alloimmunization against human platelet antigen (HPA)-1a during pregnancy can cause foetal/neonatal alloimmune thrombocytopenia (FNAIT) and severe bleeding in the foetus or newborn and likely depends on several factors. HPA-1a alloimmunization is associated with DRB3*01:01, which is associated with several DR-DQ haplotypes. However, it is not known to what extent these haplotypes contribute to the prevalence of HPA-1a alloimmunization. HPA-1a-alloimmunized women, identified in a prospective study, and random donors were typed for selected DRB3, DRB4, DRB1, DQA1 and DQB1 alleles to determine allele and DR-DQ haplotype frequencies. DRB3*01:01 was carried by 94% HPA-1a-immunized women compared to 27% in the general population. In the first population, the DR3-DQ2 haplotype was overrepresented (P < .003). The prevalence of HPA-1a alloimmunization was estimated to be about twice as frequent with DR3-DQ2 compared to DR13-DQ6, together accounting for about 90% of DRB3*01:01-positive individuals. Further, we examined DQB1*02 and DRB4*01:01 alleles for their reported association with HPA-1a alloimmunization, in the context of DR-DQ haplotypes. Since ~ 80% of DQB1*02 alleles are linked to the DR3-DQ2 haplotype, the association might be coincidental. However, the DQB1*02:02-associated DR7-DQ2 haplotype was also overrepresented in alloimmunized women, suggesting a role for this allele or haplotype in HPA-1a alloimmunization. As DRB4*01:01 is predominantly associated with the DR7-DQ2 haplotype in HPA-1a-alloimmunized individuals, the reported association with FNAIT may be coincidental. Typing for DR-DQ haplotypes revealed important genetic associations with HPA-1a alloimmunization not evident from typing individual alleles, and the presence of different DRB3-associated DR-DQ haplotypes showed different prevalence of HPA-1a alloimmunization.


Assuntos
Antígenos de Plaquetas Humanas/imunologia , Predisposição Genética para Doença/genética , Antígenos HLA-DQ/genética , Cadeias HLA-DRB3/genética , Trombocitopenia Neonatal Aloimune/genética , Feminino , Frequência do Gene/genética , Técnicas de Genotipagem , Haplótipos/genética , Humanos , Recém-Nascido , Gravidez , Trombocitopenia Neonatal Aloimune/imunologia , Trombocitopenia Neonatal Aloimune/patologia
2.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(1): 296-299, 2020 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-32027292

RESUMO

OBJECTIVE: To establise the bank of platelet donors with the human platelet antigen (HPA) 1-6, 15 genes so as to provide the HPA-matched platelets for the patients. METHODS: The HPA genotyping of platelets donors and patients with platelet antibody positive confirmed by sercening was performed by using the SSP-PCR; the efficacy of transfusing the HPA-matched platelets for 37 cases platelet antibody positive was analyzed. RESULTS: The most common genotype in platelet donors were HPA-1a/1a-2a/2a-3a/3b-4a/4a-5a/5a-6a/6a-15a/15b, followed by HPA-1a/1a-2a/2a-3a/3a-4a/4a-5a/5a-6a/6a-15a/15b; the most common genotype in 53 cases of platelet antibody positive confirened by screening were HPA-1a/1a-2a/2a-3a/3b-4a/4a-5a/5a-6a/6a-15a/15b. Among 37 patients with platelet antibody positive confirened by screeming, 28 showed that the transfusion of HPA-matched platelets was effective with statistically significant difference in comparison with random transfusion group. The HPA-3, HPA-15 were the main factors leading to polymorphisms. CONCLUSION: HPA-3 and HPA-15 are polymorphic, which should be focused on. HPA-matched platelets can improve the efficiency of platelet transfusion, and avoid the waste of blood resources. The genotypes of platelet donors can basically meet the requirements for common genotype transfusion.


Assuntos
Plaquetas , Antígenos de Plaquetas Humanas , Doadores de Sangue , Frequência do Gene , Genótipo , Humanos , Polimorfismo Genético
3.
Rev Soc Bras Med Trop ; 53: e20190210, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31994660

RESUMO

INTRODUCTION: Hepatitis C virus (HCV) infection is involved in the pathogenesis of autoimmune and rheumatic disorders. Although the human platelet antigens (HPA) polymorphism are associated with HCV persistence, they have not been investigated in rheumatological manifestations (RM). This study focused on verifying associations between allele and genotype HPA and RM in patients with chronic hepatitis C. METHODS: Patients (159) with chronic hepatitis C of both genders were analyzed. RESULTS: Women showed association between HPA-3 polymorphisms and RM. CONCLUSIONS: An unprecedented strong association between rheumatological manifestations and HPA-3 polymorphism, possibly predisposing women to complications during the disease course, was observed.


Assuntos
Antígenos de Plaquetas Humanas/genética , Hepatite C Crônica/sangue , Hepatite C Crônica/complicações , Polimorfismo Genético/genética , Doenças Reumáticas/sangue , Doenças Reumáticas/etiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Antígenos de Plaquetas Humanas/sangue , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Adulto Jovem
4.
Immunogenetics ; 72(1-2): 49-55, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31641782

RESUMO

The Immuno Polymorphism Database (IPD), https://www.ebi.ac.uk/ipd/, is a set of specialist databases that enable the study of polymorphic genes which function as part of the vertebrate immune system. The major focus is on the hyperpolymorphic major histocompatibility complex (MHC) genes and the killer-cell immunoglobulin-like receptor (KIR) genes, by providing the official repository and primary source of sequence data. Databases are centred around humans as well as animals important for food security, for companionship and as disease models. The IPD project works with specialist groups or nomenclature committees who provide and manually curate individual sections before they are submitted for online publication. To reflect the recent advance of allele sequencing technologies and the increasing demands of novel tools for the analysis of genomic variation, the IPD project is undergoing a progressive redesign and reorganisation. In this review, recent updates and future developments are discussed, with a focus on the core concepts to better future-proof the project.


Assuntos
Antígenos de Plaquetas Humanas/genética , Complexo Principal de Histocompatibilidade/genética , Biologia Computacional/métodos , Bases de Dados como Assunto , Bases de Dados Factuais , Bases de Dados Genéticas , Epitopos de Linfócito T/genética , Antígenos HLA/genética , Humanos , Imunidade/genética , Polimorfismo Genético/genética , Alinhamento de Sequência/estatística & dados numéricos
5.
Blood ; 134(22): e1-e8, 2019 11 28.
Artigo em Inglês | MEDLINE | ID: mdl-31697836

RESUMO

Human platelet membrane glycoprotein polymorphisms can be immunogenic in man and are frequently the cause of clinically important immune reactions responsible for disorders such as neonatal alloimmune thrombocytopenia. Platelets from individuals carrying rare polymorphisms are often difficult to obtain, making diagnostic testing and transfusion of matched platelets challenging. In addition, class I HLA antibodies frequently present in maternal sera interfere with the detection of platelet-reactive alloantibodies. Detection of alloantibodies to human platelet antigen 3 (HPA-3) and HPA-9 is especially challenging, in part because of the presence of cell type-specific glycans situated near the polymorphic amino acid that together form the alloepitope. To overcome these limitations, we generated a series of HLA class I-negative blood group O induced pluripotent stem cell (iPSC) lines that were gene edited to sequentially convert their endogenous HPA-3a alloantigenic epitope to HPA-3b, and HPA-9a to HPA-9b. Subjecting these cell lines, upon differentiation into CD41+/CD42b+ human megakaryocytes (MKs), to flow cytometric detection of suspected anti-HPA-3 and HPA-9 alloantisera revealed that the HPA-3a-positive MKs specifically reacted with HPA-3a patient sera, whereas the HPA-3b MKs lost reactivity with HPA-3a patient sera while acquiring reactivity to HPA-3b patient sera. Importantly, HPA-9b-expressing MKs specifically reacted with anti-HPA-9b-suspected patient samples that had been undetectable using conventional techniques. The provision of specialized iPSC-derived human MKs expressing intact homozygous glycoprotein alloantigens on the cell surface that carry the appropriate endogenous carbohydrate moieties should greatly enhance detection of clinically important and rare HPA-specific alloantibodies that, to date, have resisted detection using current methods.


Assuntos
Antígenos de Plaquetas Humanas/imunologia , Engenharia Celular , Células-Tronco Pluripotentes Induzidas/imunologia , Isoanticorpos/imunologia , Megacariócitos/imunologia , Antígenos de Plaquetas Humanas/genética , Antígenos de Plaquetas Humanas/metabolismo , Citometria de Fluxo , Humanos , Células-Tronco Pluripotentes Induzidas/metabolismo , Isoanticorpos/sangue , Megacariócitos/metabolismo
7.
Int J Med Mushrooms ; 21(8): 793-804, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31679286

RESUMO

Our earlier work indicated that the polysaccharides of Amauroderma rude (AR) appear to have an effect on immunoregulation. However, the pathways are not clear. In this paper, we discuss the immunomodulatory mechanisms of A. rude to provide a scientific basis for its possible use as a food. Amauroderma rude increased the expression of iNOS and P38 in the Raw246.7 cell line. When the AR concentration reached 150 µg/mL, the expressions of iNOS and P38 increased 23.0% and 191.7%, respectively. When the AR concentrations were 50 µg/mL, the concentrations of cytokines IL-2, TNF-α, and IFN-γ were 33.65 pg/mL, 12.53 pg/mL and 42.56 pg/mL. When AR reached 200 µg/mL, the lgA and lgM levels were 0.73 µg/mL and 1.5 µg/mL. When AR reached 400 µg/mL, the lgG level reached 1.65 µg/mL by ELISA assay. When 4.8 mg AR were orally administered, IL-2, TNF-α, IFN-γ, PGE2, and LTB4 increased dramatically, to 0.17 pg/mL, 0.16 pg/mL, 0.15 pg/mL, 30.71 pg/mL, and 18.68 pg/mL, respectively. The concentrations of lgA, lgM, and lgG, AA, and PLA2 also increased significantly to 2.62 pg/mL, 2.14 pg/mL, 2.06 pg/mL, 5.23 µg/mL and 3.68 ng/mL, respectively. With 4.8 mg AR p.o., iNOS protein expression increased 16.8% and P38 increased 234.0%. These results indicate that A. rude polysaccharides stimulate cytokine production and activate the iNOS, PLA2-AA, and MAPK pathways during the immunomodulatory process.


Assuntos
Antígenos de Plaquetas Humanas/imunologia , Fatores Imunológicos/farmacologia , Óxido Nítrico Sintase Tipo II/imunologia , Polyporaceae/química , Polissacarídeos/farmacologia , Transdução de Sinais/efeitos dos fármacos , Agaricales , Animais , Linhagem Celular , Citocinas/metabolismo , Ensaio de Imunoadsorção Enzimática , Camundongos , Fator de Necrose Tumoral alfa/metabolismo
8.
Thromb Haemost ; 119(11): 1807-1815, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31587244

RESUMO

BACKGROUND: Fetal/neonatal alloimmune thrombocytopenia (FNAIT) results from maternal alloantibodies (abs) reacting with fetal platelets expressing paternal human platelet antigens (HPAs), mostly HPA-1a. Anti-HPA-1a abs, are the most frequent cause of severe thrombocytopenia and intracranial hemorrhage (ICH). OBJECTIVES: Titration of anti-HPA-1a in maternal serum using standard National Institute for Biological Standards and Control (NIBSC) 03/152 is one diagnostic approach to predict the severity of FNAIT. Recently, we found three anti-HPA-1a subtypes reacting with the ß3 subunit independently or dependently from complexes with αIIb and αv. Endothelial cell-reactive anti-αvß3 abs were found predominantly in cases with ICH. Our aim was to assess whether available standard material represents all anti-HPA-1a subtypes. MATERIALS AND METHODS: In this study, anti-HPA-1a sera (NIBSC 03/152) and human monoclonal antibodies (moabs) against HPA-1a (moabs 26.4 and 813) were evaluated using transfected cell lines expressing αIIbß3, αvß3 or monomeric cß3. RESULTS: Flow cytometry analyses with well-characterized murine moabs recognizing αIIbß3, αvß3, or ß3 alone demonstrated that AP3 reacts compound-independently, whereas compound-dependent moabs Gi5 and 23C6 reacted only with complexes. NIBSC 03/152, moabs 26.4, and 813 against HPA-1a reacted like AP3, same results were obtained with monomeric cß3 in immunoblotting. Antigen capture assay targeting endothelial cells showed anti-HPA-1a reactivity disappearance after cß3 beads adsorption. Furthermore, in contrast to anti-HPA-1a abs from ICH cases, none of NIBSC 03/152, 26.4, and 813 inhibited tube formation. CONCLUSION: These results suggest that current anti-HPA-1a standard material contains only the anti-ß3 subtype. The absence of anti-αvß3 makes NIBSC 03/152 less suitable as standard to predict the severity of FNAIT.


Assuntos
Anticorpos Monoclonais/imunologia , Especificidade de Anticorpos , Antígenos de Plaquetas Humanas/imunologia , Testes Imunológicos , Integrina alfaVbeta3/imunologia , Integrina beta3/imunologia , Isoanticorpos/imunologia , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/imunologia , Trombocitopenia Neonatal Aloimune/diagnóstico , Células Endoteliais/imunologia , Células HEK293 , Humanos , Isoanticorpos/sangue , Neovascularização Fisiológica , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Índice de Gravidade de Doença , Trombocitopenia Neonatal Aloimune/sangue , Trombocitopenia Neonatal Aloimune/imunologia
9.
Rev Soc Bras Med Trop ; 52: e20170427, 2019 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-31271612

RESUMO

INTRODUCTION: HPA polymorphism has been associated with HCV presence and fibrosis progression in chronic hepatitis C. However, it is unknown if there is an association between HPA-1 polymorphism and hepatocellular carcinoma (HCC). Therefore, this study aimed to evaluate HPA-1 polymorphism in the presence of HCC. METHODS: PCR-SSP was used to perform HPA genotyping on 76 HCV-infected patients. RESULTS: There was no association between patients with and without HCC. There was significant difference in HPA-1 genotypic frequency distribution between HCC and F1/F2 fibrosis degree. CONCLUSIONS: The HPA-1a/1b polymorphism appears to be more associated with liver damage progression than with HCC presence.


Assuntos
Antígenos de Plaquetas Humanas/genética , Carcinoma Hepatocelular/virologia , Hepatite C Crônica/genética , Neoplasias Hepáticas/virologia , Carcinoma Hepatocelular/genética , Progressão da Doença , Feminino , Marcadores Genéticos , Genótipo , Hepatite C Crônica/virologia , Humanos , Neoplasias Hepáticas/genética , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Prognóstico , Fatores de Risco
10.
Transfus Clin Biol ; 26(3): 152-154, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31277985

RESUMO

The complement is a key player of the innate immune response. It provides defense mechanisms that are not specific, but very efficient at neutralizing any invader, accounting for 4% of the proteins in the peripheral blood. Nevertheless, there is a dark side to the complement system, as it may activate its machinery against healthy cells such as peripheral blood red blood cells and platelets resulting in undesired hemolysis and thrombocytopenia, respectively. Understanding and identifying the role of complement in these settings allow physicians to adjust their diagnostic and therapeutic modalities accordingly. The role of complement in the pathophysiology and management of autoimmune hemolytic anemia and of alloimmune-mediated thrombocytopenia is under investigation and discussed.


Assuntos
Anemia Hemolítica Autoimune/imunologia , Proteínas do Sistema Complemento/imunologia , Imunidade Inata/imunologia , Transfusão de Plaquetas , Anemia Hemolítica Autoimune/terapia , Especificidade de Anticorpos , Antígenos de Plaquetas Humanas/imunologia , Soro Antilinfocitário/sangue , Soro Antilinfocitário/imunologia , Autoanticorpos/sangue , Autoanticorpos/imunologia , Humanos , Imunoglobulina G/imunologia , Imunoglobulina M/imunologia
11.
Kobe J Med Sci ; 64(6): E197-E199, 2019 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-31327862

RESUMO

Antibodies against fetal platelet alloantigens in maternal blood cause neonatal alloimmune thrombocytopenia (NAIT). We encountered four newborns with NAIT from three women. A woman carried anti-human platelet antigen (HPA)-1a antibody, and vaginally delivered a newborn who had subarachnoid hemorrhage and platelet transfusions. She delivered the second newborn by a cesarean section who had no symptom. The second woman carried anti-human leukocyte antigen-A2 antibody and vaginally delivered a newborn who had no symptom. The third woman with a history of recurrent pregnancy losses carried anti-HPA-4b antibody, and delivered a newborn by a cesarean section who received platelet transfusions and immunoglobulin infusions. Antiplatelet antibody screening may be helpful in women who have a history of blood transfusion, or previous neonates with thrombocytopenia or intracranial hemorrhage.


Assuntos
Trombocitopenia Neonatal Aloimune/terapia , Adulto , Antígenos de Plaquetas Humanas/imunologia , Feminino , Humanos , Recém-Nascido , Transfusão de Plaquetas
13.
Allergol Int ; 68(4): 450-455, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31064688

RESUMO

BACKGROUND: Given increased risk of cardiovascular events in asthma we hypothesized that lipoprotein-associated phospholipase A2 (Lp-PLA2), an enzyme involved in atherosclerosis, is associated with proinflammatory and prothrombotic blood alterations in this disease. METHODS: In 164 adult asthmatics (63 with severe asthma) we measured plasma Lp-PLA2 activity using the PLAC test. We determined its relations to inflammation and prothrombotic blood alterations. RESULTS: In asthma, Lp-PLA2 was inversely related to the age (ß = -0.1 [-0.18 to -0.02]) and was lower in women (n = 122 [74%], 205 [182-242] vs. 243 [203-262] nmol/min/ml, p = 0.001). Interestingly, Lp-PLA2 correlated negatively with the asthma severity score (ß = -0.15 [-0.23 to -0.07]), being 10.3% higher in those with non-severe (mild or moderate) asthma (n = 101, 62%) as compared to the severe disease subtype (224 [191-261] vs. 203 [181-229], p = 0.006 after adjustment for potential confounders). Lp-PLA2 activity was positively related to the levels of low-density lipoprotein (ß = 0.1 [0.02-0.18]), triglycerides (ß = 0.11 [0.03-0.19]) and glucose (ß = 0.1 [0.02-0.18]) and inversely to the tumor necrosis factor α (ß = -0.27 [-0.35 to -0.2]), high sensitivity C-reactive protein (ß = -0.1 [-0.19 to -0.02]) and fibrinogen (ß = -0.12 [-0.21 to -0.03]), as well as prothrombin (ß = -0.16 [-0.24 to -0.08]), and parameters describing thrombin generation potential, such as endogenous thrombin potential (ß = -0.14 [-0.21 to -0.06]) and peak thrombin generated (ß = -0.2 [-0.28 to -0.12]). CONCLUSIONS: Elevated Lp-PLA2 activity in non-severe asthmatics suggests increased atherosclerotic risk in this group. Lower Lp-PLA2 activity accompanied by its inverse relationship to inflammatory or prothrombotic blood biomarkers observed in turn in severe asthmatics might be related to the pathogenesis of more severe asthma phenotype.


Assuntos
Antígenos de Plaquetas Humanas/metabolismo , Asma/imunologia , Asma/metabolismo , Adulto , Idoso , Asma/diagnóstico , Asma/tratamento farmacológico , Biomarcadores , Ativação Enzimática , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença
14.
J Perinatol ; 39(7): 920-926, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31073147

RESUMO

OBJECTIVE: To estimate the prevalence and characteristics of fetal thrombocytopenia at the time of percutaneous umbilical cord sampling (PUBS) in pregnancies complicated by alloimmunization and to conduct a systematic review on fetal thrombocytopenia in these pregnancies. STUDY DESIGN: Retrospective cohort study of all patients undergoing PUBS at our institution from 2000-2017. Clinical data, including fetal platelet counts, were abstracted from the medical record and analyzed with routine statistical procedures. A systematic review and meta-analysis were also conducted according to standard procedures. RESULT: At first procedure, prior to any transfusion, 13/36 fetuses (36%) had thrombocytopenia: 11/36 (31%) had moderate thrombocytopenia and 2/36 (6%) had severe thrombocytopenia (14 patients had no platelet count at first procedure). The systematic review identified six studies, and the prevalence of fetal thrombocytopenia at the time of PUBS for alloimmunization was 18% (95% confidence interval 11%, 26%). CONCLUSION: Thrombocytopenia is common and underappreciated in fetuses undergoing PUBS for alloimmunization.


Assuntos
Incompatibilidade de Grupos Sanguíneos/complicações , Sangue Fetal , Doenças Fetais/etiologia , Trombocitopenia/etiologia , Anemia/diagnóstico , Anemia/etiologia , Antígenos de Plaquetas Humanas/imunologia , Feminino , Sangue Fetal/citologia , Fetoscopia , Idade Gestacional , Humanos , Contagem de Plaquetas , Gravidez , Complicações Hematológicas na Gravidez , Estudos Retrospectivos , Trombocitopenia/diagnóstico , Trombocitopenia/imunologia
15.
Int J Mol Sci ; 20(9)2019 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-31060339

RESUMO

The lipidic prodrug approach is an emerging field for improving a number of biopharmaceutical and drug delivery aspects. Owing to their structure and nature, phospholipid (PL)-based prodrugs may join endogenous lipid processing pathways, and hence significantly improve the pharmacokinetics and/or bioavailability of the drug. Additional advantages of this approach include drug targeting by enzyme-triggered drug release, blood-brain barrier permeability, lymphatic targeting, overcoming drug resistance, or enabling appropriate formulation. The PL-prodrug design includes various structural modalities-different conjugation strategies and/or the use of linkers between the PL and the drug moiety, which considerably influence the prodrug characteristics and the consequent effects. In this article, we describe how molecular modeling can guide the structural design of PL-based prodrugs. Computational simulations can predict the extent of phospholipase A2 (PLA2)-mediated activation, and facilitate prodrug development. Several computational methods have been used to facilitate the design of the pro-drugs, which will be reviewed here, including molecular docking, the free energy perturbation method, molecular dynamics simulations, and free density functional theory. Altogether, the studies described in this article indicate that computational simulation-guided PL-based prodrug molecular design correlates well with the experimental results, allowing for more mechanistic and less empirical development. In the future, the use of molecular modeling techniques to predict the activity of PL-prodrugs should be used earlier in the development process.


Assuntos
Desenho de Fármacos , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Fosfolipídeos/química , Pró-Fármacos/química , Animais , Antígenos de Plaquetas Humanas/química , Humanos , Estrutura Molecular , Especificidade por Substrato
16.
Medicine (Baltimore) ; 98(19): e15440, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31083173

RESUMO

RATIONALE: Neonatal alloimmune thrombocytopenia (NAIT) caused by anti HPA-3a antibody is rare, and the clinical features of the syndrome are not specific. PATIENT CONCERNS: A male infant was noted to be irritable and physical examination revealed the presence of petechiae and bruising on the right arm and thigh after born. DIAGNOSES: Platelet antibodies were investigated using the monoclonal antibody-specific immobilization of platelet antigens (MAIPA) assay, platelet genotyping (HPA 1-17) was performed by polymerase chain reaction technique with sequence-specific primers (PCR-SSP). The HPA genotype of the newborn was HPA-3a/b, while that of his mother and his father were HPA-3b/b and HPA-3a/a, respectively. The sera of newborn contained antibody against the platelet of newborn's father. The HPA antibody of the newborn was identified as anti HPA-3a. The newborn was confirmed as a patient of NAIT caused by anti HPA-3a antibody. INTERVENTIONS: A single dose of intravenous immunoglobulin (IVIG) 1 g/kg was administered from day 3 to day 7. OUTCOMES: At follow-up 3 months after discharge from the hospital, the baby was developing normally and had a normal platelet count (361 × 109/L). LESSONS: NAIT caused by anti HPA-3a antibody is rare, and we believe this study can provide insights for diagnosing prospective cases. Prognosis of NAIT caused by HPA3a seems to be favorable if diagnosed and treated in a timely manner.


Assuntos
Antígenos de Plaquetas Humanas/imunologia , Autoanticorpos/imunologia , Trombocitopenia Neonatal Aloimune/diagnóstico , Trombocitopenia Neonatal Aloimune/terapia , Diagnóstico Diferencial , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Fatores Imunológicos/uso terapêutico , Recém-Nascido , Masculino , Trombocitopenia Neonatal Aloimune/imunologia
17.
BJOG ; 126(10): e173-e185, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-30968555

RESUMO

WHAT IS IT?: Fetal neonatal alloimmune thrombocytopenia (FNAIT), also known as neonatal alloimmune thrombocytopenia (NAIT) or fetomaternal alloimmune thrombocytopenia (FMAIT), is a rare condition which affects a baby's platelets. This can put them at risk of problems with bleeding, particularly into the brain. One baby per week in the UK may be seriously affected and milder forms can affect one in every 1000 births. HOW IS IT CAUSED?: Platelets are blood cells that are very important in helping blood to clot. All platelets have natural proteins on their surface called human platelet antigens (HPAs). In babies, half of these antigens are inherited from the mother and half from the father. During pregnancy, some of the baby's platelets can cross into the mother's bloodstream. In most cases, this does not cause a problem. But in cases of FNAIT, the mother's immune system does not recognise the baby's HPAs that were inherited from the father and develops antibodies, which can cross the placenta and attack the baby's platelets. These antibodies are called anti-HPAs, and the commonest antibody implicated is anti-HPA-1a, but there are other rarer antibody types. If this happens, the baby's platelets may be destroyed causing their platelet count to fall dangerously low. If the platelet count is very low there is a risk to the baby of bleeding into their brain before they are born. This is very rare but if it happens it can have serious effects on the baby's health. HOW IS IT INHERITED?: A baby inherits half of their HPAs from its mother and half from its father. Consequently, a baby may have different HPAs from its mother. As the condition is very rare, and even if the baby is at risk of the condition we have no way of knowing how severely they will be affected, routine screening is not currently recommended. WHAT CAN BE DONE?: FNAIT is usually diagnosed if a previous baby has had a low platelet count. The parents are offered blood tests and the condition can be confirmed or ruled out. There are many other causes of low platelets in babies, which may also need to be tested for. As the condition is so rare, expertise is limited to specialist centres and normally a haematologist and fetal medicine doctor will perform and interpret the tests together. Fortunately, there is an effective treatment for the vast majority of cases called immunoglobulin, or IVIg. This 'blood product' is given intravenously through a drip every week to women at risk of the condition. It may be started from as early as 16 weeks in the next pregnancy, until birth, which would be offered at around 36-37 weeks. Less common treatments that may be considered depending on individual circumstances include steroid tablets or injections, or giving platelet transfusions to the baby. WHAT DOES THIS PAPER TELL YOU?: This paper considers the latest evidence in relation to treatment options in the management of pregnancies at risk of FNAIT. Specifically, we discuss the role of screening, when IVIg should be started, what dose should be used, and what evidence there is for maternal steroids. We also consider in very rare selected cases, the use of fetal blood sampling and giving platelet transfusions to the baby before birth. Finally, we consider the approaches to blood testing mothers to tell if babies are at risk, which is offered in some countries, and development of new treatments to reduce the risk of FNAIT.


Assuntos
Doenças Fetais/genética , Imunoglobulinas Intravenosas/uso terapêutico , Doenças do Recém-Nascido/genética , Programas de Rastreamento/métodos , Cuidado Pré-Natal/métodos , Trombocitopenia Neonatal Aloimune/diagnóstico , Trombocitopenia Neonatal Aloimune/prevenção & controle , Antígenos de Plaquetas Humanas , Feminino , Doenças Fetais/prevenção & controle , Doenças Fetais/terapia , Testes Genéticos , Humanos , Recém-Nascido , Doenças do Recém-Nascido/terapia , Anamnese , Contagem de Plaquetas , Gravidez , Trombocitopenia Neonatal Aloimune/genética , Trombocitopenia Neonatal Aloimune/terapia
18.
Neth J Med ; 77(2): 81-83, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30895931

RESUMO

Post-transfusion purpura (PTP) is a rare, but severe transfusion reaction in which both donor and autologous platelets are sequestered due to immunization against HPA-1a antigens in HPA-1a negative recipients (HPA: human platelet antigens). We describe a patient who developed PTP during induction therapy for acute myeloid leukaemia. The pitfalls, delays in diagnosing and therapy options of this serious transfusion reaction are discussed.


Assuntos
Púrpura/etiologia , Trombocitopenia/imunologia , Reação Transfusional/complicações , Antígenos de Plaquetas Humanas , Transfusão de Sangue , Feminino , Humanos , Leucemia Mieloide Aguda/terapia , Pessoa de Meia-Idade , Trombocitopenia/diagnóstico
19.
Br J Haematol ; 185(3): 549-562, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30828796

RESUMO

Fetal and neonatal alloimmune thrombocytopenia (FNAIT) may result in severe bleeding, particularly fetal and neonatal intracranial haemorrhage (ICH). As a result, FNAIT requires prompt identification and treatment; subsequent pregnancies need close surveillance and management. An international panel convened to develop evidence-based recommendations for diagnosis and management of FNAIT. A rigorous approach was used to search, review and develop recommendations from published data for: antenatal management, postnatal management, diagnostic testing and universal screening. To confirm FNAIT, fetal human platelet antigen (HPA) typing, using non-invasive methods if quality-assured, should be performed during pregnancy when the father is unknown, unavailable for testing or heterozygous for the implicated antigen. Women with a previous child with an ICH related to FNAIT should be offered intravenous immunoglobulin (IVIG) infusions during subsequent affected pregnancies as early as 12 weeks gestation. Ideally, HPA-selected platelets should be available at delivery for potentially affected infants and used to increase the neonatal platelet count as needed. If HPA-selected platelets are not immediately available, unselected platelets should be transfused. FNAIT studies that optimize antenatal and postnatal management, develop risk stratification algorithms to guide management and standardize laboratory testing to identify high risk pregnancies are needed.


Assuntos
Medicina Baseada em Evidências , Doenças Fetais , Imunoglobulinas Intravenosas/uso terapêutico , Hemorragias Intracranianas , Trombocitopenia Neonatal Aloimune , Antígenos de Plaquetas Humanas/sangue , Feminino , Doenças Fetais/diagnóstico , Doenças Fetais/tratamento farmacológico , Doenças Fetais/epidemiologia , Humanos , Recém-Nascido , Hemorragias Intracranianas/sangue , Hemorragias Intracranianas/diagnóstico , Hemorragias Intracranianas/tratamento farmacológico , Hemorragias Intracranianas/epidemiologia , Gravidez , Trombocitopenia Neonatal Aloimune/sangue , Trombocitopenia Neonatal Aloimune/diagnóstico , Trombocitopenia Neonatal Aloimune/tratamento farmacológico , Trombocitopenia Neonatal Aloimune/epidemiologia
20.
Artigo em Inglês | MEDLINE | ID: mdl-30827816

RESUMO

Foetal or neonatal thrombocytopenia results from alloimmunisation during pregnancy. Maternal alloantibodies can be formed following exposure to paternally derived human platelet antigens (HPAs) on foetal platelets, in case of incompatible HPA type. These alloantibodies are of the immunoglobulin G subclass and can therefore enter the foetal circulation through active placental transport mediated by the neonatal Fc-receptor. After entering the foetal circulation, these alloantibodies can cause destruction of foetal platelets and potentially damage other foetal cells containing the specific antigen. Subsequent clinical presentation in foetuses or neonates can vary widely, from an asymptomatic thrombocytopenia to a broad spectrum of bleeding complications. Most frequently encountered are minor skin haemorrhages, such as hematomas or petechiae, but also more devastating haemorrhages can occur. Of these, an intracranial haemorrhage is the most feared complication because of its high risk of life-long major neurological handicaps or perinatal death.


Assuntos
Antígenos de Plaquetas Humanas/sangue , Autoanticorpos/sangue , Imunoglobulinas Intravenosas/uso terapêutico , Trombocitopenia Neonatal Aloimune , Animais , Transfusão de Sangue Intrauterina/métodos , Feminino , Doenças Fetais/sangue , Doenças Fetais/diagnóstico , Doenças Fetais/terapia , Humanos , Recém-Nascido , Hemorragias Intracranianas/etiologia , Gravidez , Cuidado Pré-Natal/métodos , Trombocitopenia Neonatal Aloimune/sangue , Trombocitopenia Neonatal Aloimune/diagnóstico , Trombocitopenia Neonatal Aloimune/terapia
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