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1.
Medicine (Baltimore) ; 99(52): e23831, 2020 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-33350770

RESUMO

ABSTRACT: The International Society on Thrombosis and Haemostasis (ISTH) scoring system has been used for diagnosing overt disseminated intravascular coagulation (DIC). However, the cut-off points of fibrin-related markers remain unclear. The ability of the ISTH DIC score and Multiple Organ Dysfunction (MODS) score to predict mortality in cases of exertional heat illness (EHI) was tested. In the process, 3 different D-dimer cut-off values for diagnosing overt DIC were evaluated.Data were obtained on the first day of hospitalization for 76 patients with EHI. The DIC score was calculated according to the ISTH scoring system using 3 D-dimer cut-off values.In predicting mortality, methods 1 and 2 had the same sensitivity and specificity, which were 85% and 73.2%, respectively. The sensitivity for method 3 was 70%. Furthermore, the specificity of the DIC score for method 3 was 89%, which was higher than that of the other 2 methods. The correlation coefficients of the DIC and MODS scores of these 3 methods were 0.757, 0.748, and 0.756, respectively. For the prediction of mortality, the area under the receiver operating characteristic (ROC) curve for the DIC scores of these 3 methods was 0.838, 0.842, and 0.85, respectively. Furthermore, the area under the ROC curve of the MODS score was 0.927.The DIC score had a certain predictive power of a poor outcome of EHI patients, but this was not better than the MODS score. The present data may serve as a reference in selecting the appropriate D-dimer cut-off point for the ISTH DIC score.


Assuntos
Coagulação Intravascular Disseminada , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Transtornos de Estresse por Calor , Escores de Disfunção Orgânica , Adulto , China , Coagulação Intravascular Disseminada/sangue , Coagulação Intravascular Disseminada/diagnóstico , Feminino , Transtornos de Estresse por Calor/sangue , Transtornos de Estresse por Calor/diagnóstico , Transtornos de Estresse por Calor/mortalidade , Humanos , Masculino , Avaliação de Resultados em Cuidados de Saúde/métodos , Valor Preditivo dos Testes , Prognóstico , Curva ROC , Projetos de Pesquisa/normas , Sensibilidade e Especificidade
2.
Isr Med Assoc J ; 22(10): 613-617, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-33070484

RESUMO

BACKGROUND: An association was shown between thrombocytosis and future development of several cancers. OBJECTIVES: To investigate whether pre-treatment platelet counts correlated with clinical outcomes of patients with breast cancer. METHODS: This retrospective study included 22 patients who had been diagnosed with stage I breast cancer and were 66.8 ± 13.2 years of age. Of these, 22 with stage II were 61.6 ± 12.3 years old and 9 with stage III and IV were 64.4 ± 15.3 years old. Clinical and hematological data from the first visit to the oncology clinic were collected. The follow-up period was 12 months to 5 years. RESULTS: A significant difference in platelet counts was found between patients who died (187,000 ± 4000 µ/L) and those who were disease free for 5 years (248,000 ± 83,000 µ/L, P = 0.0001). A significant difference in platelet-to-lymphocyte ratio was found between patients who died and those with recurrence (192 ± 81 vs. 124 ± 71, P = 0.01). A negative correlation was found between age and lymph nodes (Ps = -0.305, P = 0.02) and staging and white blood cells count (Ps = -0.280, P = 0.04). A positive correlation was found between clinical staging and lymph nodes (Ps = 0.443, P = 0.001) and clinical staging and metastases (P = 0.308, P = 0.02). CONCLUSIONS: Platelet counts may be a prognostic marker for breast cancer. Patients who died within 1 year had lower pre-treatment platelet count, which could represent an insidious disseminated intravascular coagulopathy cancer related consumption process.


Assuntos
Neoplasias da Mama/epidemiologia , Neoplasias da Mama/patologia , Coagulação Intravascular Disseminada/epidemiologia , Trombocitose/epidemiologia , Idoso , Biomarcadores/análise , Plaquetas/fisiologia , Neoplasias da Mama/sangue , Estudos de Coortes , Comorbidade , Coagulação Intravascular Disseminada/sangue , Feminino , Humanos , Incidência , Israel , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Contagem de Plaquetas , Prognóstico , Estudos Retrospectivos , Medição de Risco , Análise de Sobrevida , Trombocitose/diagnóstico
3.
Thromb Res ; 195: 62-68, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32659462

RESUMO

BACKGROUND: Early detection of suspected critical patients infected with coronavirus disease 2019 (COVID-19) is very important for the treatment of patients. This study aimed to investigate the role of COVID-19 associated coagulopathy (CAC) to preview and triage. METHODS AND RESULTS: A cohort study was designed from government designated COVID-19 treatment center. CAC was defined as International Society on Thrombosis and Haemostasis (ISTH) score ≥2. Data from 117 patients COVID-19 were reviewed on admission. The primary and secondary outcomes were admission to Intensive Care Unit (ICU), the use of mechanical ventilation, vital organ dysfunction, discharges of days 14, 21 and 28 from admission and hospital mortality. Among them, admission to ICU was increased progressively from 16.1% in patients with non-CAC to 42.6% in patients with CAC (P < 0.01). Likely, invasive ventilation and noninvasive ventilation were increased from 1.8%, 21.4% in patients with non-CAC to 21.3%, 52.5% in patients with CAC, respectively (P < 0.01). The incidences of acute hepatic injury and acute respiratory distress syndrome in non-CAC and CAC were 28.6% vs. 62.3%, 8.9% vs. 27.9%, respectively (P < 0.01). The discharges of days 14, 21 and 28 from admission were more in non-CAC than those of CAC (P < 0.05). Multiple logistic regression results showed that ISTH score ≥2 was obviously associated with the admission to ICU (OR 4.07, 95% CI 1.47-11.25 P = 0.007) and the use of mechanical ventilation (OR 5.54, 95% CI 2.01-15.28 P = 0.001) in patients with COVID-19. CONCLUSION: All results show ISTH score ≥2 is an important indicator to preview and triage for COVID-19 patients.


Assuntos
Infecções por Coronavirus/complicações , Coagulação Intravascular Disseminada/etiologia , Pneumonia Viral/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Betacoronavirus/isolamento & purificação , China/epidemiologia , Infecções por Coronavirus/sangue , Infecções por Coronavirus/terapia , Coagulação Intravascular Disseminada/sangue , Coagulação Intravascular Disseminada/terapia , Feminino , Hospitalização , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/sangue , Pneumonia Viral/terapia , Respiração Artificial , Estudos Retrospectivos , Resultado do Tratamento
5.
Curr Probl Cardiol ; 45(9): 100648, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32703535

RESUMO

The exceptional outbreak of COVID-19 pandemic has let the scientific community to work closely and quickly learnt things in a very short period of time. This has let us recognize that thromboembolic complications are responsible for morbidity and mortality among the COVID-19 infected patients. Available data have suggested a possible multifactorial basis of these complications, and while efforts are being made to treat this infection, preventive measures with the use of systemic anticoagulation were quickly adopted to deal with this issue. Despite obvious benefits as appeared with the use of systemic anticoagulation, most of the emerged data were retrospective, hence raise questions on the possible interplay of the confounders as well as long-term benefits and safety of systemic anticoagulation.


Assuntos
Anticoagulantes/uso terapêutico , Transtornos da Coagulação Sanguínea/sangue , Infecções por Coronavirus/sangue , Pneumonia Viral/sangue , Tromboembolia/sangue , Betacoronavirus , Transtornos da Coagulação Sanguínea/tratamento farmacológico , Transtornos da Coagulação Sanguínea/etiologia , Infecções por Coronavirus/complicações , Infecções por Coronavirus/tratamento farmacológico , Coagulação Intravascular Disseminada/sangue , Coagulação Intravascular Disseminada/tratamento farmacológico , Coagulação Intravascular Disseminada/etiologia , Células Endoteliais , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Heparina/uso terapêutico , Heparina de Baixo Peso Molecular/uso terapêutico , Humanos , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/tratamento farmacológico , Tromboembolia/tratamento farmacológico , Tromboembolia/etiologia , Receptores Toll-Like/metabolismo , Fator de von Willebrand/metabolismo
6.
Eur J Clin Invest ; 50(7): e13311, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32511751
8.
Hamostaseologie ; 40(3): 264-269, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32498097

RESUMO

The novel coronavirus, SARS-CoV-2, is causing a global pandemic of life-threatening multiorgan disease, called COVID-19. Accumulating evidence indicates that patients with COVID-19 are at significant risk of thromboembolic complications, mainly affecting the venous, but also the arterial vascular system. While the risk of venous thromboembolism (VTE) appears to be higher in patients requiring intensive care unit support compared to those admitted to general wards, recent autopsy findings and data on the timing of VTE diagnosis relative to hospitalization clearly suggest that thromboembolic events also contribute to morbidity and mortality in the ambulatory setting. In addition to a severe hypercoagulable state caused by systemic inflammation and viral endotheliitis, some patients with advanced COVID-19 may develop a coagulopathy, which meets established laboratory criteria for disseminated intravascular coagulation, but is not typically associated with relevant bleeding. Similar to other medical societies, the Society of Thrombosis and Haemostasis Research has issued empirical recommendations on initiation, dosing, and duration of pharmacological VTE prophylaxis in COVID-19 patients.


Assuntos
Transtornos da Coagulação Sanguínea/etiologia , Infecções por Coronavirus/complicações , Pneumonia Viral/complicações , Tromboembolia Venosa/prevenção & controle , Anticoagulantes/uso terapêutico , Autopsia/estatística & dados numéricos , Betacoronavirus/isolamento & purificação , Transtornos da Coagulação Sanguínea/epidemiologia , Estudos de Casos e Controles , China/epidemiologia , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/patologia , Infecções por Coronavirus/virologia , Coagulação Intravascular Disseminada/sangue , Coagulação Intravascular Disseminada/diagnóstico , Coagulação Intravascular Disseminada/fisiopatologia , Heparina de Baixo Peso Molecular/uso terapêutico , Hospitalização , Humanos , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/patologia , Pneumonia Viral/virologia , Sobreviventes/estatística & dados numéricos , Síndrome de Resposta Inflamatória Sistêmica/fisiopatologia , Síndrome de Resposta Inflamatória Sistêmica/virologia , Trombofilia/etiologia , Tromboembolia Venosa/tratamento farmacológico , Tromboembolia Venosa/mortalidade
11.
Transl Res ; 222: 1-16, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32417429

RESUMO

Disseminated intravascular coagulation (DIC) is a frequent complication of sepsis that affects patient outcomes due to accompanying thrombo-inflammation and microvascular permeability changes. Platelet endothelial cell adhesion molecule-1 (PECAM-1), a cellular adhesion and signaling receptor that is expressed on both hematopoietic and endothelial cells, plays an important anti-inflammatory role in acute and chronic inflammatory disease models. Little is known, however, about role and mechanism of PECAM-1 in septic DIC. Here, we investigated whether PECAM-1 might play a protective role in hindering the development of septic DIC. Plasma levels of soluble PECAM-1 were markedly elevated in septic patients that developed DIC, with a correspondingly poorer outcome. PECAM-1 knockout exhibited more severe DIC and poorer outcome in the LPS induced- and cecal ligation and puncture-induced DIC model, which could be alleviated by tissue factor inhibitor. This phenomenon seemed to be equally linked to PECAM-1 expression by both endothelial and blood cells. Furthermore, PECAM-1 was found to exert its protective effect on developing septic DIC by the following 2 distinct mechanisms: the inhibition of macrophage pyroptosis and the acceleration of the restoration of the endothelial cell barrier. Taken together, these results implicate PECAM-1 as a potentially attractive target for the development of novel therapeutics to manage and treat septic DIC.


Assuntos
Vasos Sanguíneos/patologia , Coagulação Intravascular Disseminada/prevenção & controle , Inflamação/patologia , Macrófagos/patologia , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo , Piroptose , Animais , Coagulação Intravascular Disseminada/sangue , Coagulação Intravascular Disseminada/complicações , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Feminino , Fibrinólise , Humanos , Lipopolissacarídeos , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Pessoa de Meia-Idade , Fenótipo , Molécula-1 de Adesão Celular Endotelial a Plaquetas/sangue , Molécula-1 de Adesão Celular Endotelial a Plaquetas/deficiência , Sepse/sangue , Sepse/complicações , Resultado do Tratamento
14.
Platelets ; 31(6): 740-745, 2020 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-32456506

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the coronavirus disease in 2019 (COVID-19) which rapidly evolved from an outbreak in Wuhan, China into a pandemic that has resulted in over millions of infections and over hundreds of thousands of mortalities worldwide. Various coagulopathies have been reported in association with COVID-19, including disseminated intravascular coagulation (DIC), sepsis-induced coagulopathy (SIC), local microthrombi, venous thromboembolism (VTE), arterial thrombotic complications, and thrombo-inflammation. There is a plethora of publications and conflicting data on hematological and hemostatic derangements in COVID-19 with some data suggesting the link to disease progress, severity and/or mortality. There is also growing evidence of potentially useful clinical biomarkers to predict COVID-19 progression and disease outcomes. Of those, a link between thrombocytopenia and COVID-19 severity or mortality was suggested. In this opinion report, we examine the published evidence of hematological and hemostatic laboratory derangements in COVID-19 and the interrelated SARS-CoV-2 induced inflammation, with a focussed discussion on platelet count alterations. We explore whether thrombocytopenia could be a potential disease biomarker and we provide recommendations for future studies in this regard.


Assuntos
Betacoronavirus , Transtornos da Coagulação Sanguínea/etiologia , Infecções por Coronavirus/sangue , Pandemias , Contagem de Plaquetas , Pneumonia Viral/sangue , Trombocitopenia/etiologia , Trombocitose/etiologia , Contagem de Células Sanguíneas , Transtornos da Coagulação Sanguínea/sangue , Testes de Coagulação Sanguínea , Infecções por Coronavirus/complicações , Coagulação Intravascular Disseminada/sangue , Coagulação Intravascular Disseminada/etiologia , Humanos , Inflamação/sangue , Inflamação/etiologia , Pneumonia Viral/complicações , Tromboelastografia , Trombocitopenia/sangue , Trombocitose/sangue , Trombofilia/sangue , Trombofilia/etiologia
16.
Br J Haematol ; 189(5): 846-847, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32304577

RESUMO

Emerging evidence shows that severe coronavirus disease 2019 (COVID-19) can be complicated with coagulopathy, namely disseminated intravascular coagulation, which has a rather prothrombotic character with high risk of venous thromboembolism. The incidence of venous thromboembolism among COVID-19 patients in intensive care units appears to be somewhat higher compared to that reported in other studies including such patients with other disease conditions. D-dimer might help in early recognition of these high-risk patients and also predict outcome. Preliminary data show that in patients with severe COVID-19, anticoagulant therapy appears to be associated with lower mortality in the subpopulation meeting sepsis-induced coagulopathy criteria or with markedly elevated d-dimer. Recent recommendations suggest that all hospitalized COVID-19 patients should receive thromboprophylaxis, or full therapeutic-intensity anticoagulation if such an indication is present.


Assuntos
Anticoagulantes/administração & dosagem , Betacoronavirus , Infecções por Coronavirus , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Pandemias , Pneumonia Viral , Tromboembolia Venosa , Infecções por Coronavirus/sangue , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/epidemiologia , Coagulação Intravascular Disseminada/sangue , Coagulação Intravascular Disseminada/tratamento farmacológico , Coagulação Intravascular Disseminada/epidemiologia , Coagulação Intravascular Disseminada/virologia , Feminino , Humanos , Incidência , Masculino , Pneumonia Viral/sangue , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/epidemiologia , Fatores de Risco , Tromboembolia Venosa/sangue , Tromboembolia Venosa/tratamento farmacológico , Tromboembolia Venosa/epidemiologia , Tromboembolia Venosa/virologia
17.
Am J Hematol ; 95(7): 834-847, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32282949

RESUMO

COVID-19 is a systemic infection with a significant impact on the hematopoietic system and hemostasis. Lymphopenia may be considered as a cardinal laboratory finding, with prognostic potential. Neutrophil/lymphocyte ratio and peak platelet/lymphocyte ratio may also have prognostic value in determining severe cases. During the disease course, longitudinal evaluation of lymphocyte count dynamics and inflammatory indices, including LDH, CRP and IL-6 may help to identify cases with dismal prognosis and prompt intervention in order to improve outcomes. Biomarkers, such high serum procalcitonin and ferritin have also emerged as poor prognostic factors. Furthermore, blood hypercoagulability is common among hospitalized COVID-19 patients. Elevated D-Dimer levels are consistently reported, whereas their gradual increase during disease course is particularly associated with disease worsening. Other coagulation abnormalities such as PT and aPTT prolongation, fibrin degradation products increase, with severe thrombocytopenia lead to life-threatening disseminated intravascular coagulation (DIC), which necessitates continuous vigilance and prompt intervention. So, COVID-19 infected patients, whether hospitalized or ambulatory, are at high risk for venous thromboembolism, and an early and prolonged pharmacological thromboprophylaxis with low molecular weight heparin is highly recommended. Last but not least, the need for assuring blood donations during the pandemic is also highlighted.


Assuntos
Betacoronavirus , Infecções por Coronavirus/sangue , Linfopenia/etiologia , Pneumonia Viral/sangue , Trombofilia/etiologia , Anticoagulantes/uso terapêutico , Biomarcadores , Testes de Coagulação Sanguínea , Doadores de Sangue/provisão & distribução , Proteína C-Reativa/análise , Técnicas de Laboratório Clínico , Infecções por Coronavirus/complicações , Infecções por Coronavirus/diagnóstico , Síndrome da Liberação de Citocina/sangue , Síndrome da Liberação de Citocina/etiologia , Citocinas/sangue , Coagulação Intravascular Disseminada/sangue , Coagulação Intravascular Disseminada/etiologia , Diagnóstico Precoce , Ferritinas/sangue , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Humanos , Metanálise como Assunto , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/diagnóstico , Risco , Trombofilia/sangue , Trombofilia/tratamento farmacológico , Tromboembolia Venosa/sangue , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/prevenção & controle
18.
J Thromb Haemost ; 18(7): 1648-1652, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32302459

RESUMO

We present a putative link between maternal COVID-19 infection in the peripartum period and rapid maternal deterioration with early organ dysfunction and coagulopathy. The current pandemic with SARS-CoV-2 has already resulted in high numbers of critically ill patients and deaths in the non-pregnant population, mainly due to respiratory failure. During viral outbreaks, pregnancy poses a uniquely increased risk to women due to changes to immune function, alongside physiological adaptive alterations, such as increased oxygen consumption and edema of the respiratory tract. The laboratory derangements may be reminiscent of HELLP (hemolysis, elevated liver enzymes, low platelet count) syndrome, and thus knowledge of the COVID-19 relationship is paramount for appropriate diagnosis and management. In addition to routine measurements of D-dimers, prothrombin time, and platelet count in all patients presenting with COVID-19 as per International Society on Thrombosis and Haemostasis (ISTH) guidance, monitoring of activated partial thromboplastin time (APTT) and fibrinogen levels should be considered in pregnancy, as highlighted in this report. These investigations in SARS-CoV-2-positive pregnant women are vital, as their derangement may signal a more severe COVID-19 infection, and may warrant pre-emptive admission and consideration of delivery to achieve maternal stabilization.


Assuntos
Betacoronavirus/patogenicidade , Coagulação Sanguínea , Infecções por Coronavirus/virologia , Coagulação Intravascular Disseminada/virologia , Pneumonia Viral/virologia , Complicações Hematológicas na Gravidez/virologia , Complicações Infecciosas na Gravidez/virologia , Adulto , Testes de Coagulação Sanguínea , Técnicas de Laboratório Clínico , Infecções por Coronavirus/sangue , Infecções por Coronavirus/diagnóstico , Coagulação Intravascular Disseminada/sangue , Coagulação Intravascular Disseminada/diagnóstico , Coagulação Intravascular Disseminada/terapia , Feminino , Interações Hospedeiro-Patógeno , Humanos , Pandemias , Pneumonia Viral/sangue , Pneumonia Viral/diagnóstico , Gravidez , Complicações Hematológicas na Gravidez/sangue , Complicações Hematológicas na Gravidez/diagnóstico , Complicações Hematológicas na Gravidez/terapia , Complicações Infecciosas na Gravidez/sangue , Complicações Infecciosas na Gravidez/diagnóstico , Complicações Infecciosas na Gravidez/terapia , Terceiro Trimestre da Gravidez/sangue , Resultado do Tratamento , Adulto Jovem
19.
PLoS One ; 15(3): e0229616, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32130237

RESUMO

BACKGROUND: The aim of this study was to characterize the time-resolved progression of clinical laboratory disturbances days-following an exertional heat stroke (EHS). Currently, normalization of organ injury clinical biomarker values is the primary indicator of EHS recovery. However, an archetypical biochemical recovery profile following EHS has not been established. METHODS: We performed a retrospective analysis of EHS patient records in US military personnel from 2008-2014 using the Military Health System Data Repository (MDR). We focused on commonly reported clinical laboratory analytes measured on the day of injury and all proceeding follow-up visits. RESULTS: Over the prescribed period, there were 2,529 EHS episodes treated at 250 unique treatment locations. Laboratory results, including a standardized set of blood, serum and urine assays, were analyzed from 0-340 days following the initial injury. Indicators of acute kidney injury, including serum electrolyte disturbances and abnormal urinalysis findings, were most prevalent on the day of the injury but normalized within 24-48hours (creatinine, blood urea nitrogen, and blood and protein in urine). Muscle damage and liver function-associated markers peaked 0-4 days after injury and persisted outside their respective reference ranges for 2-16 days (alanine aminotransferase, aspartate aminotransferase, creatine phosphokinase, myoglobin, prothrombin time). CONCLUSION: Biochemical recovery from EHS spans a 16-day time course, and markers of end-organ damage exhibit distinct patterns over this period. This analysis underscores the prognostic value of each clinical laboratory analyte and will assist in evaluating EHS patient presentation, injury severity and physiological recovery.


Assuntos
Golpe de Calor/sangue , Golpe de Calor/urina , Esforço Físico/fisiologia , Lesão Renal Aguda/sangue , Lesão Renal Aguda/etiologia , Lesão Renal Aguda/urina , Adulto , Biomarcadores/sangue , Biomarcadores/urina , Nitrogênio da Ureia Sanguínea , Creatinina/sangue , Coagulação Intravascular Disseminada/sangue , Coagulação Intravascular Disseminada/etiologia , Feminino , Insuficiência Hepática/sangue , Insuficiência Hepática/etiologia , Insuficiência Hepática/urina , Humanos , Masculino , Saúde Militar , Militares , Músculos/lesões , Mioglobina/sangue , Estudos Retrospectivos , Fatores de Tempo , Estados Unidos , Adulto Jovem
20.
Blood ; 135(14): 1087-1100, 2020 04 02.
Artigo em Inglês | MEDLINE | ID: mdl-32016282

RESUMO

Bacterial infection not only stimulates innate immune responses but also activates coagulation cascades. Overactivation of the coagulation system in bacterial sepsis leads to disseminated intravascular coagulation (DIC), a life-threatening condition. However, the mechanisms by which bacterial infection activates the coagulation cascade are not fully understood. Here we show that type 1 interferons (IFNs), a widely expressed family of cytokines that orchestrate innate antiviral and antibacterial immunity, mediate bacterial infection-induced DIC by amplifying the release of high-mobility group box 1 (HMGB1) into the bloodstream. Inhibition of the expression of type 1 IFNs and disruption of their receptor IFN-α/ßR or downstream effector (eg, HMGB1) uniformly decreased gram-negative bacteria-induced DIC. Mechanistically, extracellular HMGB1 markedly increased the procoagulant activity of tissue factor by promoting the externalization of phosphatidylserine to the outer cell surface, where phosphatidylserine assembles a complex of cofactor-proteases of the coagulation cascades. These findings not only provide novel insights into the link between innate immune responses and coagulation, but they also open a new avenue for developing novel therapeutic strategies to prevent DIC in sepsis.


Assuntos
Coagulação Intravascular Disseminada/imunologia , Endotoxemia/imunologia , Bactérias Gram-Negativas/imunologia , Infecções por Bactérias Gram-Negativas/imunologia , Interferon-alfa/imunologia , Interferon beta/imunologia , Proteínas Adaptadoras de Transporte Vesicular/imunologia , Animais , Coagulação Sanguínea , Coagulação Intravascular Disseminada/sangue , Coagulação Intravascular Disseminada/etiologia , Endotoxemia/sangue , Endotoxemia/complicações , Infecções por Bactérias Gram-Negativas/sangue , Infecções por Bactérias Gram-Negativas/complicações , Proteína HMGB1/sangue , Proteína HMGB1/imunologia , Humanos , Imunidade Inata , Camundongos Endogâmicos C57BL
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