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1.
Autoimmun Rev ; 18(11): 102395, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31520800

RESUMO

BACKGROUND: According to criteria for the classification of Systemic Lupus Erythematosus (SLE), thrombocytopenia is one of the disease-defining hematologic disorders. Since the recognition of Antiphospholipid Syndrome (APS), thrombocytopenia was frequently reported but several studies yielded contradictory results on the association between aPL-positivity and thrombocytopenia. METHODS: We evaluated the role of antiphospholipid antibodies (aPL) and different aPL profiles on the risk of thrombocytopenia in SLE patients by conducting a systematic review and meta-analysis of available literature from 1987 to 2018. MEDLINE, EMBASE, Cochrane Library, congress abstracts, and reference lists of eligible studies were searched. Studies were selected if they included SLE patients with descriptions of the exposure to aPL and the outcomes (thrombocytopenia). Two reviewers extracted study characteristics and outcome data from published reports. Estimates were pooled using random effects models and sensitivity analyses. We followed the PRISMA guidelines for all stages of the meta-analysis. PROSPERO registration number: CRD42015027378. RESULTS: From 3278 articles identified, 53 studies met inclusion criteria amounting to 9019 SLE patients. Twenty-nine percent of aPL-positive SLE patients had thrombocytopenia compared to 15.1% in aPL-negative SLE patients. The overall pooled Odds Ratio (OR) for thrombocytopenia in aPL positive patients was 2.48 (95% CI; 2.10-2.93). Among aPL subtypes, the risk of thrombocytopenia was highest for lupus anticoagulant (OR = 3.56 [95% CI, 2.57-5.25]), IgM anti-ß2-GP1(OR = 2.87 [95% CI; 2.57-5.25]), IgG and IgM anticardiolipin antibodies (OR = 1.87 [95% CI; 1.52-2.31] and OR = 1.73 [95% CI; 1.36-2.19] respectively). CONCLUSIONS: The occurrence of thrombocytopenia was strongly determined by various aPL profiles in SLE patients. While the association between IgM antibodies and other APS manifestations including thrombosis is debated, IgM isotypes are helpful in the risk stratification of thrombocytopenia in SLE.


Assuntos
Anticorpos Antifosfolipídeos/imunologia , Lúpus Eritematoso Sistêmico/epidemiologia , Trombocitopenia/epidemiologia , Estudos de Casos e Controles , Estudos de Coortes , Estudos Transversais , Humanos , Lúpus Eritematoso Sistêmico/imunologia , Fatores de Risco , Trombocitopenia/imunologia
2.
BMJ Case Rep ; 12(9)2019 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-31488440

RESUMO

We present a case of a 47-year-old man with severe thrombocytopenia. The differential diagnosis for thrombocytopenia is wide. The assessment includes an evaluation for falsely low platelet counts (pseudothrombocytopenia), immune-mediated platelet destruction, bone marrow dysfunction, or increased consumption and sequestration. After extensive and systematic workup, we found a relationship of his thrombocytopenia with haemodialysis. Although not widely recognised by clinicians, partly due to an incomplete understanding of its pathophysiology, haemodialysis is also a potential cause of thrombocytopenia. His platelet counts completely normalised after the substitution of his haemodialysis membrane. We concluded that our patient had haemodialysis-induced thrombocytopenia, most likely secondary to electron-beam sterilisation.


Assuntos
Membranas Artificiais , Diálise Renal/efeitos adversos , Trombocitopenia/etiologia , Materiais Biocompatíveis/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Polímeros/uso terapêutico , Diálise Renal/instrumentação , Esterilização , Sulfonas/uso terapêutico , Trombocitopenia/imunologia
3.
BMC Res Notes ; 12(1): 604, 2019 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-31547852

RESUMO

OBJECTIVE: Objective of the study is to evaluate the on-admission day symptoms and signs, clinical, hematological parameters and liver transaminases of the dengue NS1 positive patients who got admitted on different clinical phases [Febrile phase (day 1-3) and Critical phase(day 4-5)] of dengue at medical wards of Jaffna Teaching Hospital. RESULTS: Blood samples were collected from 150 suspected dengue patients from day 1 to 5 of the illness. Seventy-eight patients were positive for dengue NS1, according to the WHO proposed dengue clinical phase framework 37 patients were from febrile phase and 41 patients from critical phase. Patients who admitted on critical phase framework suffered from leukopenia and thrombocytopenia. Nine patients had the evidence of leakage with fever and the leakers had significant rise in hemoglobin, hematocrit and liver transaminase levels which are considered as severe form of the disease.


Assuntos
Vírus da Dengue/patogenicidade , Febre/diagnóstico , Hospitais de Ensino , Leucopenia/diagnóstico , Dengue Grave/diagnóstico , Trombocitopenia/diagnóstico , Proteínas não Estruturais Virais/sangue , Adolescente , Adulto , Vírus da Dengue/imunologia , Progressão da Doença , Feminino , Febre/sangue , Febre/imunologia , Febre/virologia , Hospitalização , Humanos , Leucopenia/sangue , Leucopenia/imunologia , Leucopenia/virologia , Fígado/patologia , Fígado/virologia , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Dengue Grave/sangue , Dengue Grave/imunologia , Dengue Grave/virologia , Sri Lanka , Trombocitopenia/sangue , Trombocitopenia/imunologia , Trombocitopenia/virologia , Transaminases/sangue , Proteínas não Estruturais Virais/imunologia
4.
Hematology ; 24(1): 588-595, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31392938

RESUMO

Objective: To explore the activity of B subsets from Autoimmune Hemolytic Anemia/Evans syndrome (AIHA/ES) patients. Methods: The expression of Bruton's tyrosine kinase (BTK) and phosphorylated BTK (p-BTK) on CD5+CD19+B and CD5-CD19+B lymphocytes were detected using flow cytometry in AIHA/ES patients with different disease states, healthy controls (HCs) and chronic lymphocytic leukemia (CLL) patients. The correlations of expressed BTK and p-BTK with clinical variables were analyzed. Results: Thirty six AIHA/ES patients (16 hemolytic, 20 remission), 11 CLL patients, and 15 HCs were enrolled. The expression levels of BTK and p-BTK on CD5+B lymphocytes in AIHA/ES patients were higher than those in HCs and CLL patients. The latter two groups had no significant difference, and were positively correlated with the quantity of IgE. The ratio of p-BTK to BTK on CD5+B lymphocytes of the hemolytic and remission groups was obviously higher than that on CD5-B lymphocytes (74.62 ± 6.42% and 29.63 ± 10.19%, respectively; P = 0.001 versus 77.95 ± 9.57% and 26.29 ± 6.86%, respectively; P = 0.006). The ratio of p-BTK to BTK on CD5+B lymphocytes (54.89 ± 9.56%) and CD5-B lymphocytes (30.86 ± 12.47%) did not differ significantly in HCs (P = 0.109). BTK did not differ significantly between CD5+ and CD5-B lymphocytes in AIHA/ES, but p-BTK on CD5+B lymphocytes was significantly higher than that on CD5-B lymphocytes in AIHA/ES patients. Conclusions: CD5+B lymphocytes are the major B subtype that is activated in AIHA/ES patients and it positively correlates with IgE.


Assuntos
Tirosina Quinase da Agamaglobulinemia/metabolismo , Anemia Hemolítica Autoimune/imunologia , Linfócitos B/metabolismo , Trombocitopenia/imunologia , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
5.
BMJ Case Rep ; 12(7)2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31371330

RESUMO

Thrombocytopaenia can be associated with an autoimmune mechanism. Immune thrombocytopaenia can be associated with thyroid autoimmune disease. The authors present a case of a teenager with a history of thrombocytopaenia who complained of tiredness. Laboratory investigation showed thyroid autoantibodies. The co-existence of thrombocytopaenia and thyroiditis lead to further investigation and antibodies against platelet glycoprotein IIbIIIa were found. This case illustrates the association of the overlap aspects between thyroid and platelet autoimmunity.


Assuntos
Autoanticorpos/imunologia , Trombocitopenia/imunologia , Tireoidite Autoimune/imunologia , Adolescente , Autoanticorpos/sangue , Feminino , Humanos , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/imunologia , Trombocitopenia/sangue , Tireoidite Autoimune/sangue
6.
Thromb Haemost ; 119(6): 941-951, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31005061

RESUMO

BACKGROUND: Heparin-induced thrombocytopenia (HIT) antibodies activate platelets, monocytes and neutrophils. Despite these findings, it is unknown whether white blood cell (WBC) counts, including neutrophils and monocytes, are altered during HIT. MATERIALS AND METHODS: We evaluated changes in total WBC counts (including WBC subsets), in 50 post-cardiac surgery patients with serologically confirmed HIT (30 patients with HIT-associated thrombosis). Daily leukocyte counts were compared with those measured one day prior to HIT onset; WBC increases were classified as mild (20.0-49.9%), moderate (50.0-99.9%) or major (≥ 100% increase). We also compared changes in WBC counts in HIT patients with and without HIT-associated thrombosis, and non-HIT patients with thrombosis. RESULTS: Most (34/50 [68.0%]) patients with HIT developed WBC count increases (mild, 35.3%; moderate, 44.1%; major, 20.6%). The peak WBC count occurred on day 4 (median) of HIT, which corresponded to day 10 (median) post-surgery. Absolute neutrophil counts increased in most patients (38/50 [76.0%]); whereas absolute monocyte counts rose in some patients, the overall tendency was for the monocyte count to decrease during HIT. Unexpectedly, we found that the increase in total WBC counts, as well as in neutrophils, was seen mainly in patients who developed HIT-associated or non-HIT-associated thrombosis; in contrast, no difference in monocyte levels was seen in patients with or without thrombosis. CONCLUSION: Leukocytosis and neutrophilia are commonly observed in patients with HIT, particularly in patients with HIT-associated thrombosis, as well as non-HIT patients with thrombosis. Thus, leukocytosis/neutrophilia should not infer automatically a diagnosis of infection or inflammation, when evaluating thrombocytopenia in heparin-exposed patients.


Assuntos
Anticoagulantes/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/imunologia , Monócitos/imunologia , Neutrófilos/imunologia , Trombocitopenia/imunologia , Anticoagulantes/uso terapêutico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/diagnóstico , Heparina/metabolismo , Humanos , Contagem de Leucócitos , Leucocitose , Neutropenia , Estudos Retrospectivos , Trombocitopenia/diagnóstico , Trombocitopenia/etiologia , Trombose
7.
Blood ; 134(1): 9-21, 2019 07 04.
Artigo em Inglês | MEDLINE | ID: mdl-30940614

RESUMO

Evans syndrome (ES) is a rare severe autoimmune disorder characterized by the combination of autoimmune hemolytic anemia and immune thrombocytopenia. In most cases, the underlying cause is unknown. We sought to identify genetic defects in pediatric ES (pES), based on a hypothesis of strong genetic determinism. In a national, prospective cohort of 203 patients with early-onset ES (median [range] age at last follow-up: 16.3 years ([1.2-41.0 years]) initiated in 2004, 80 nonselected consecutive individuals underwent genetic testing. The clinical data were analyzed as a function of the genetic findings. Fifty-two patients (65%) received a genetic diagnosis (the M+ group): 49 carried germline mutations and 3 carried somatic variants. Thirty-two (40%) had pathogenic mutations in 1 of 9 genes known to be involved in primary immunodeficiencies (TNFRSF6, CTLA4, STAT3, PIK3CD, CBL, ADAR1, LRBA, RAG1, and KRAS), whereas 20 patients (25%) carried probable pathogenic variants in 16 genes that had not previously been reported in the context of autoimmune disease. Lastly, no genetic abnormalities were found in the remaining 28 patients (35%, the M- group). The M+ group displayed more severe disease than the M- group, with a greater frequency of additional immunopathologic manifestations and a greater median number of lines of treatment. Six patients (all from the M+ group) died during the study. In conclusion, pES was potentially genetically determined in at least 65% of cases. Systematic, wide-ranging genetic screening should be offered in pES; the genetic findings have prognostic significance and may guide the choice of a targeted treatment.


Assuntos
Anemia Hemolítica Autoimune/genética , Anemia Hemolítica Autoimune/imunologia , Trombocitopenia/genética , Trombocitopenia/imunologia , Adolescente , Adulto , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Lactente , Masculino , Mutação , Adulto Jovem
8.
Nat Commun ; 10(1): 1322, 2019 03 21.
Artigo em Inglês | MEDLINE | ID: mdl-30899022

RESUMO

Heparin-induced thrombocytopenia/thrombosis (HIT) is a serious immune reaction to heparins, characterized by thrombocytopenia and often severe thrombosis with high morbidity and mortality. HIT is mediated by IgG antibodies against heparin/platelet factor 4 antigenic complexes. These complexes are thought to activate platelets leading to thrombocytopenia and thrombosis. Here we show that HIT immune complexes induce NETosis via interaction with FcγRIIa on neutrophils and through neutrophil-platelet association. HIT immune complexes induce formation of thrombi containing neutrophils, extracellular DNA, citrullinated histone H3 and platelets in a microfluidics system and in vivo, while neutrophil depletion abolishes thrombus formation. Absence of PAD4 or PAD4 inhibition with GSK484 abrogates thrombus formation but not thrombocytopenia, suggesting they are induced by separate mechanisms. NETs markers and neutrophils undergoing NETosis are present in HIT patients. Our findings demonstrating the involvement of NETosis in thrombosis will modify the current concept of HIT pathogenesis and may lead to new therapeutic strategies.


Assuntos
Plaquetas/imunologia , Armadilhas Extracelulares/imunologia , Heparina/efeitos adversos , Neutrófilos/imunologia , Receptores de IgG/genética , Trombocitopenia/imunologia , Trombose/imunologia , Animais , Complexo Antígeno-Anticorpo/biossíntese , Plaquetas/efeitos dos fármacos , Citrulinação , Inibidores Enzimáticos/farmacologia , Armadilhas Extracelulares/química , Armadilhas Extracelulares/efeitos dos fármacos , Regulação da Expressão Gênica , Histonas/genética , Histonas/imunologia , Humanos , Imunoglobulina G/biossíntese , Camundongos , Camundongos Transgênicos , Técnicas Analíticas Microfluídicas , Ativação de Neutrófilo/efeitos dos fármacos , Ativação de Neutrófilo/imunologia , Neutrófilos/efeitos dos fármacos , Ativação Plaquetária/efeitos dos fármacos , Ativação Plaquetária/imunologia , Fator Plaquetário 4/genética , Fator Plaquetário 4/imunologia , Desiminases de Arginina em Proteínas/antagonistas & inibidores , Desiminases de Arginina em Proteínas/genética , Desiminases de Arginina em Proteínas/imunologia , Receptores de IgG/imunologia , Transdução de Sinais , Trombocitopenia/induzido quimicamente , Trombocitopenia/patologia , Trombose/induzido quimicamente , Trombose/patologia , Trombose/prevenção & controle
9.
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
10.
J Infect Dis ; 220(1): 23-27, 2019 06 05.
Artigo em Inglês | MEDLINE | ID: mdl-30721983

RESUMO

Atypical lymphocytes in the peripheral blood in patients with severe fever with thrombocytopenia syndrome (SFTS) have not been well examined. In this study, we analyzed counts and characteristics of atypical lymphocytes in 7 patients with SFTS. Atypical lymphocytes resembled plasma cells morphologically and appeared in the peripheral blood of all patients 4-8 days after onset of disease. Among these lymphocytes flow cytometry showed a CD19+CD38+CD138-/+ phenotype, and immunohistochemical staining revealed a CD79a+CD38+CD138-/+CD27+ phenotype. From our observations, atypical lymphocytes transiently that appeared in the peripheral blood during the acute phase of SFTS were considered to be plasmablasts.


Assuntos
Linfócitos/imunologia , Plasmócitos/imunologia , Trombocitopenia/imunologia , Idoso , Idoso de 80 Anos ou mais , Antígenos CD/imunologia , Grupo com Ancestrais do Continente Asiático , Feminino , Febre/imunologia , Citometria de Fluxo/métodos , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Fenótipo
12.
PLoS Pathog ; 15(2): e1007375, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30707748

RESUMO

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease localized to China, Japan, and Korea that is characterized by severe hemorrhage and a high fatality rate. Currently, no specific vaccine or treatment has been approved for this disease. To develop a therapeutic agent for SFTS, we isolated antibodies from a phage-displayed antibody library that was constructed from a patient who recovered from SFTS virus (SFTSV) infection. One antibody, designated as Ab10, was reactive to the Gn envelope glycoprotein of SFTSV and protected host cells and A129 mice from infection in both in vitro and in vivo experiments. Notably, Ab10 protected 80% of mice, even when injected 5 days after inoculation with a lethal dose of SFTSV. Using cross-linker assisted mass spectrometry and alanine scanning, we located the non-linear epitope of Ab10 on the Gn glycoprotein domain II and an unstructured stem region, suggesting that Ab10 may inhibit a conformational alteration that is critical for cell membrane fusion between the virus and host cell. Ab10 reacted to recombinant Gn glycoprotein in Gangwon/Korea/2012, HB28, and SD4 strains. Additionally, based on its epitope, we predict that Ab10 binds the Gn glycoprotein in 247 of 272 SFTSV isolates previously reported. Together, these data suggest that Ab10 has potential to be developed into a therapeutic agent that could protect against more than 90% of reported SFTSV isolates.


Assuntos
Anticorpos Neutralizantes/metabolismo , Phlebovirus/imunologia , Adulto , Animais , Anticorpos Neutralizantes/fisiologia , Anticorpos Antivirais/metabolismo , Infecções por Bunyaviridae/terapia , Epitopos/imunologia , Feminino , Febre , Glutamina/imunologia , Glutamina/metabolismo , Glicoproteínas/imunologia , Células HEK293 , Humanos , Leucopenia , Masculino , Camundongos , Camundongos Knockout , Testes de Neutralização , Phlebovirus/patogenicidade , República da Coreia , Trombocitopenia/imunologia , Proteínas do Envelope Viral/imunologia
13.
Curr Protoc Toxicol ; 79(1): e68, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30673165

RESUMO

Phagocytosis of platelets by monocytes and macrophages is a primary mechanism of platelet clearance in vivo and has been increasingly implicated in playing an important role in thrombocytopenia mediated by monoclonal antibodies intended for therapeutic purposes. In the present article, we describe an in vitro flow cytometry assay to assess the effect of antibody-mediated platelet phagocytosis by monocytes. Freshly isolated platelets were labeled with a fluorescent probe, 5-chloromethylfluorescein diacetate (CMFDA) and then co-cultured with isolated peripheral blood mononuclear cells (PBMCs) from the same donor in the presence of increasing concentrations of a monoclonal antibody drug. After incubation, an increase in CMFDA fluorescence intensity of CD14 positive monocytes was evaluated by flow cytometry as an assessment for drug-mediated platelet phagocytosis by monocytes. The assay has been evaluated using both human and cynomolgus monkey cells for the prediction of drug-induced thrombocytopenia. © 2019 by John Wiley & Sons, Inc.


Assuntos
Anticorpos Monoclonais/efeitos adversos , Bioensaio/métodos , Plaquetas/efeitos dos fármacos , Leucócitos Mononucleares/efeitos dos fármacos , Fagocitose/efeitos dos fármacos , Trombocitopenia/induzido quimicamente , Animais , Plaquetas/imunologia , Técnicas de Cocultura , Citometria de Fluxo , Fluoresceínas/química , Corantes Fluorescentes/química , Humanos , Leucócitos Mononucleares/imunologia , Macaca fascicularis , Fagocitose/imunologia , Valor Preditivo dos Testes , Trombocitopenia/imunologia
14.
J Thromb Thrombolysis ; 47(2): 287-291, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30612329

RESUMO

A high frequency of PF4-ELISA testing in patients suspected to have heparin-induced thrombocytopenia (HIT) despite low 4T scores has been observed in multiple medical centers. Education of clinicians has been suggested to reduce inappropriate testing. We determined trends of PF4-ELISA testing in our institution after the introduction of a HIT education program for clinicians. A HIT Program was developed that included ongoing education, individual feedback, and continuous clinical audit of PF4-ELISA utilization. To assess the impact of education on PF4-ELISA testing trends, we conducted a prospective cohort review of all adult patients who had a PF4-ELISA ordered over a 3 month period (the last quarter of the academic year). 72 PF4-ELISA tests were ordered during the study period. Prospectively calculated 4T scores by investigators revealed 60 low-risk (83.3%), 9 intermediate-risk (12.5%), and 3 high-risk (4.16%). We observed divergent 4T scores with the ordering clinician calculating a higher 4T score compared to the Hematology Quality Improvement (QI) team. The majority of PF4-ELISA testing was ordered by the intensive care units (ICUs) (n = 32, 44.44%). Our study revealed that the frequency of calculation of 4T scores remains poor with the majority inappropriately performed in the ICU setting, with ordering clinicians calculating higher 4T scores than the Hematology QI team. This suggests that clinician education alone is insufficient. Introducing mandatory 4T score calculation prior to PF4-ELISA testing may not be helpful as ordering clinicians can bypass the restriction through inaccurate 4T score calculation.


Assuntos
Anticoagulantes/efeitos adversos , Educação Médica Continuada/métodos , Educação de Pós-Graduação em Medicina/métodos , Ensaio de Imunoadsorção Enzimática , Heparina/efeitos adversos , Imunoglobulina G/sangue , Capacitação em Serviço/métodos , Fator Plaquetário 4/imunologia , Trombocitopenia/diagnóstico , Procedimentos Desnecessários , Anticoagulantes/imunologia , Biomarcadores/sangue , Tomada de Decisão Clínica , Técnicas de Apoio para a Decisão , Retroalimentação Psicológica , Conhecimentos, Atitudes e Prática em Saúde , Heparina/imunologia , Humanos , Seleção de Pacientes , Padrões de Prática Médica , Valor Preditivo dos Testes , Estudos Prospectivos , Trombocitopenia/sangue , Trombocitopenia/induzido quimicamente , Trombocitopenia/imunologia
15.
Thorac Cardiovasc Surg ; 67(1): 21-27, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-29605959

RESUMO

BACKGROUND: Heparin-induced thrombocytopenia (HIT) in infants is a rare disorder, and the diagnosis and management of HIT still remains challenging. Argatroban is a synthetic direct thrombin inhibitor (DTI) that is widely used for treating HIT. However, little is known about the efficacy of the activated clotting time (ACT) test in monitoring DTI treatment as an alternative to the routinely used activated partial thromboplastin time (aPTT). METHODS: Between July 2013 and January 2015, four infants were diagnosed with HIT after surgical correction of congenital anomalies. In all cases, heparin was used during cardiopulmonary bypass (CPB). Diagnosis of HIT was based on the "4 Ts" pretest clinical scoring system, and platelet factor 4 (PF4) antibody was detected using enzyme-linked immunosorbent assay. Argatroban was used in treating HIT. When argatroban was infused, anticoagulation tests (aPTT, prothrombin time [PT], thrombin time [TT], and fibrinogen) were performed every 4 to 12 hours. ACT was used in addition to monitor the anticoagulation effect of argatroban. The target ACT was 1.5 to 3.0 times the baseline. ACT was measured every 2 to 4 hours and remeasured 1 hour after each dosage adjustment. RESULTS: Thrombocytopenia (defined as a 50% decrease in platelet count) occurred during the 3rd to 6th day postoperatively. After the diagnosis of HIT, argatroban was started immediately, and platelet counts stabilized and gradually increased. Anticoagulation effect of argatroban was successful monitored by ACT and aPTT. Poor correlation between the ACT test and aPTT test (R = 0.270, p = 0.092) was noted in one patient. ACT values increased rapidly after 3 to 7 days on argatroban treatment. In most cases, low dosage of argatroban was given ranging from 0.04 to 5.00 µg/kg/min. CONCLUSION: Argatroban may be an effective medicine in treating HIT in infants, in a reduced dosage. The great fluctuation in argatroban dosage during the course of HIT treatment necessitates close monitoring. ACT test may be reliable and convenient for monitoring HIT treatment and may contribute to positive clinical outcomes in infants. The efficacy of argatroban and the use of ACT monitoring in the management of HIT infants needs further study.


Assuntos
Anticoagulantes/efeitos adversos , Coagulação Sanguínea/efeitos dos fármacos , Procedimentos Cirúrgicos Cardíacos , Cardiopatias Congênitas/cirurgia , Heparina/efeitos adversos , Trombocitopenia/induzido quimicamente , Anticorpos/sangue , Anticoagulantes/administração & dosagem , Anticoagulantes/imunologia , Antitrombinas/uso terapêutico , Testes de Coagulação Sanguínea , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Monitoramento de Medicamentos/métodos , Feminino , Cardiopatias Congênitas/sangue , Cardiopatias Congênitas/diagnóstico , Heparina/administração & dosagem , Heparina/imunologia , Humanos , Lactente , Masculino , Ácidos Pipecólicos/uso terapêutico , Fator Plaquetário 4/imunologia , Valor Preditivo dos Testes , Fatores de Risco , Trombocitopenia/sangue , Trombocitopenia/tratamento farmacológico , Trombocitopenia/imunologia , Resultado do Tratamento
16.
J Infect Dis ; 219(4): 648-659, 2019 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-30312422

RESUMO

Background: Infection with the gram-negative bacillus Burkholderia pseudomallei (melioidosis) is an important cause of pneumosepsis in Southeast Asia and has a mortality of up to 40%. We aimed to assess the role of platelets in the host response against B. pseudomallei infection. Methods: Association between platelet counts and mortality was determined in 1160 patients with culture-proven melioidosis. Mice treated with (low- or high-dose) platelet-depleting antibody were inoculated intranasally with B. pseudomallei and killed. Additional studies using functional glycoprotein Ibα-deficient mice were conducted. Results: Thrombocytopenia was present in 31% of patients at admission and predicted mortality in melioidosis patients even after adjustment for confounders. In our murine-melioidosis model, platelet counts decreased, and mice treated with a platelet-depleting antibody showed enhanced mortality and higher bacterial loads compared to mice with normal platelet counts. Low platelet counts had a modest impact on early-pulmonary neutrophil influx. Reminiscent of their role in hemostasis, platelet depletion impaired vascular integrity, resulting in early lung bleeding. Glycoprotein Ibα-deficient mice had reduced platelet counts during B. pseudomallei infection together with an impaired local host defense in the lung. Conclusions: Thrombocytopenia predicts mortality in melioidosis patients and, during experimental melioidosis, platelets play a protective role in both innate immunity and vascular integrity.


Assuntos
Burkholderia pseudomallei/imunologia , Melioidose/complicações , Melioidose/patologia , Trombocitopenia/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Ásia Sudeste , Modelos Animais de Doenças , Feminino , Humanos , Masculino , Melioidose/imunologia , Melioidose/mortalidade , Camundongos , Pessoa de Meia-Idade , Estudos Prospectivos , Análise de Sobrevida , Trombocitopenia/imunologia , Adulto Jovem
17.
Am J Clin Pathol ; 151(4): 353-363, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30285067

RESUMO

OBJECTIVES: To provide an overview of the complexities associated with the human leukocyte antigen (HLA)-mediated platelet refractoriness. HLA antibody detection technologies and limitations associated with methodologies are discussed. METHODS: A case scenario and review of relevant literature describing platelet refractoriness are presented, followed by a discussion of HLA antibody testing. RESULTS: Following diagnosis of HLA-mediated refractoriness, a decision is made regarding the approach to obtain the appropriate platelets. The panel reactive antibodies (PRA) % of the patient, HLA typing, and limitations of the HLA testing should be taken into account when deciding which type of product would be the best option for a given patient. CONCLUSIONS: Following confirmation and review of HLA antibody testing, platelets are ordered based upon the PRA% and approach employed, HLA-matched platelets, antigen restricted platelets, or cross-matched platelets. The platelets are transfused and a posttransfusion increment count is monitored to determine transfusion success.


Assuntos
Plaquetas/imunologia , Antígenos HLA/imunologia , Trombocitopenia/imunologia , Reação Transfusional/imunologia , Idoso de 80 Anos ou mais , Especificidade de Anticorpos/imunologia , Tipagem e Reações Cruzadas Sanguíneas , Feminino , Teste de Histocompatibilidade , Humanos , Transfusão de Plaquetas , Trombocitopenia/terapia
18.
Semin Thorac Cardiovasc Surg ; 31(3): 335-344, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30448485

RESUMO

Heparin-induced thrombocytopenia (HIT) is an immune-mediated condition characterized by thrombocytopenia with possible arterial and/or venous thrombosis. The overall incidence of HIT is low but ranges from 0.1% to 5%.1,2 The incidence can be as high as 3% in patients undergoing cardiac surgery. The use of unfractionated heparin (UFH) is ubiquitous in patients who undergo cardiac procedures and carries a 10-fold higher incidence of HIT over low molecular weight heparin. Patients undergoing cardiac surgery thus form a unique group that warrants specific attention to this clinicopathologic entity considering the relatively high incidence and associated morbidity and mortality with a delay in diagnosis. In this article, we will discuss 5 clinical aspects pertinent to the diagnosis and management of HIT in cardiac surgery patients and review the current literature.


Assuntos
Anticoagulantes/efeitos adversos , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Heparina/efeitos adversos , Trombocitopenia/induzido quimicamente , Anticorpos/sangue , Anticoagulantes/imunologia , Biomarcadores/sangue , Procedimentos Cirúrgicos Cardíacos/mortalidade , Heparina/imunologia , Humanos , Incidência , Fator Plaquetário 4/imunologia , Prognóstico , Fatores de Risco , Trombocitopenia/imunologia , Trombocitopenia/mortalidade , Trombocitopenia/terapia
19.
Int Immunopharmacol ; 66: 362-365, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30529500

RESUMO

Primary immune thrombocytopenia (ITP) is an autoimmune disease characterized by pathogenic immunoglobulin G (IgG) autoantibodies that bind to platelets, causing their phagocytic removal and leading to reductions in platelet number. The neonatal Fc receptor (FcRn) selectively salvages and recycles IgG, including pathogenic IgG, thereby extending the half-life of IgG in plasma. Two anti-mouse FcRn monoclonal antibodies (mAb) (4470 and 4464) were generated to evaluate the effect of inhibiting IgG recycling. Statistically significant reductions in plasma IgG concentration were observed upon administration of 4470 (10, 30 and 100 mg/kg) in wild-type mice. In a passive mouse model of ITP, 4464 alleviated the reduction in platelet number and/or preserved newly produced platelets when dosed prophylactically as well as in a therapeutic dosing regimen once platelet numbers had already been reduced. These results support the investigation of anti-FcRn therapy as a potential treatment for ITP.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Plaquetas/imunologia , Imunoglobulina G/sangue , Imunoglobulinas Intravenosas/uso terapêutico , Imunoterapia/métodos , Anticorpos de Cadeia Única/uso terapêutico , Trombocitopenia/terapia , Animais , Anticorpos Monoclonais/genética , Autoanticorpos/metabolismo , Linhagem Celular , Modelos Animais de Doenças , Feminino , Antígenos de Histocompatibilidade Classe I/imunologia , Humanos , Imunidade Humoral , Camundongos , Camundongos Endogâmicos C57BL , Contagem de Plaquetas , Receptores Fc/imunologia , Anticorpos de Cadeia Única/genética , Trombocitopenia/imunologia
20.
J Pediatr Hematol Oncol ; 41(2): 81-86, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30543580

RESUMO

BACKGROUND: Autoimmune thrombocytopenia in immune thrombocytopenic purpura (ITP), thrombotic thrombocytopenic purpura (TTP), and heparin-induced thrombocytopenia (HIT) is associated with immunologic degradation of platelets and reduced platelet counts in patients, leading to bleeding risk in patients. Considering the role of human leukocyte antigens (HLA) in the development of immune response, in this review, we examine the relationship between HLA and pathogenesis of the above-mentioned diseases. METHODS: Relevant English-language literature was searched and retrieved from Google Scholar search engine and PubMed database (1979 to 2018). The following keywords were used: "Immune Thrombocytopenic purpura," "Thrombotic Thrombocytopenic Purpura," Human Leukocyte Antigen," and "Heparin-induced thrombocytopenia." RESULTS: In autoimmune thrombocytopenia, HLA molecule presents self-antigens or foreign antigens similar to self-antigens, provoking an immune response against platelets that results in the degradation of platelets in peripheral blood and possible bleeding in the patient. For example, HLA-DRB1 *11 presents the self-antigen and induces an immune response against ADAMTS13, which is associated with thrombocytopenia in TTP patients. CONCLUSIONS: HLA alleles can be used as prognostic biomarkers for immunologic disorders of platelet such as ITP, TTP, and HIT. Different DRB1 alleles enable the assessment of resistance to common ITP treatments as well as disease prognosis. Due to the genetic association between HLA-DR1 and HLA-DQ1 alleles and the role of HLA-DRB1 *11 in TTP, the HLA-DQB1 *02: 02 allele may also play a role in TTP pathogenesis.


Assuntos
Antígenos HLA/imunologia , Hemorragia/imunologia , Heparina/efeitos adversos , Púrpura Trombocitopênica Idiopática/imunologia , Púrpura Trombocitopênica Trombótica/imunologia , Trombocitopenia/imunologia , Antígenos HLA/sangue , Hemorragia/sangue , Hemorragia/patologia , Humanos , Contagem de Plaquetas , Púrpura Trombocitopênica Idiopática/sangue , Púrpura Trombocitopênica Idiopática/patologia , Púrpura Trombocitopênica Trombótica/sangue , Púrpura Trombocitopênica Trombótica/patologia , Trombocitopenia/sangue , Trombocitopenia/induzido quimicamente , Trombocitopenia/patologia
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