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1.
J Surg Res ; 246: 605-613, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31668435

RESUMO

BACKGROUND: Platelet function tests such as thrombelastography platelet mapping and impedance aggregometry have demonstrated universal platelet dysfunction in trauma patients. In this study, we introduce the measurement of platelet contraction force as a test of platelet function. We hypothesize that force will correlate with established coagulation tests such as thrombelastography, demonstrate significant differences between healthy subjects and trauma patients, and identify critically ill trauma patients. METHODS: Blood samples were prospectively collected from level 1 trauma patients at initial presentation, assayed for force of and time to contraction and compared with thrombelastography. Blood from healthy subjects was assayed to establish a reference range. Results from trauma patients were compared with healthy controls and trauma patients that died. RESULTS: The study includes one hundred trauma patients with mean age 45 y, 74% were male, and median injury severity score of 14 ± 12. Patients that survived (n = 90) demonstrated significantly elevated platelet contraction force compared with healthy controls (n = 12) (6390 ± 2340 versus 4790 ± 470 µN, P = 0.043) and trauma patients that died (n = 10) (6390 ± 2340 versus 2860 ± 1830 µN, P = 0.0001). Elapsed time to start of platelet contraction was faster in trauma patients that survived compared with healthy controls (660 ± 467 versus 1130 ± 140 s, P = 0.0022) and those that died (660 ± 470 versus 1460 ± 1340 s, P < 0.0001). CONCLUSIONS: In contrast with all existing platelet function tests reported in the literature, which report platelet dysfunction in trauma patients, contractile force demonstrates hyperfunction in surviving trauma patients and dysfunction in nonsurvivors. Platelet contraction reflects platelet metabolic reserve and thus may be a potential biomarker for survival after trauma. Contractile force warrants further investigation to predict mortality in severely injured trauma patients.


Assuntos
Transtornos Plaquetários/diagnóstico , Plaquetas/fisiologia , Ferimentos e Lesões/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Coagulação Sanguínea/fisiologia , Transtornos Plaquetários/sangue , Transtornos Plaquetários/etiologia , Transtornos Plaquetários/fisiopatologia , Feminino , Humanos , Escala de Gravidade do Ferimento , Masculino , Pessoa de Meia-Idade , Testes de Função Plaquetária/métodos , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Curva ROC , Tromboelastografia , Ferimentos e Lesões/sangue , Ferimentos e Lesões/diagnóstico , Ferimentos e Lesões/mortalidade , Adulto Jovem
2.
J Trauma Acute Care Surg ; 88(2): 279-285, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31738314

RESUMO

BACKGROUND: Trauma-induced coagulopathy is a major driver of mortality following severe injury. Viscoelastic goal-directed resuscitation can reduce mortality after injury. The TEG 5000 system is widely used for viscoelastic testing. However, the TEG 6s system incorporates newer technology, with encouraging results in cardiovascular interventions. The purpose of this study was to validate the TEG 6s system for use in trauma patients. METHODS: Multicenter noninvasive observational study for method comparison conducted at 12 US Levels I and II trauma centers. Agreement between the TEG 6s and TEG 5000 systems was examined using citrated kaolin reaction time (CK.R), citrated functional fibrinogen maximum amplitude (CFF.MA), citrated kaolin percent clot lysis at 30 minutes (CK.LY30), citrated RapidTEG maximum amplitude (CRT.MA), and citrated kaolin maximum amplitude (CK.MA) parameters in adults meeting full or limited trauma team criteria. Blood was drawn ≤1 hour after admission. Assays were repeated in duplicate. Reliability (TEG 5000 vs. TEG 6s analyzers) and repeatability (interdevice comparison) was quantified. Linear regression was used to define the relationship between TEG 6s and TEG 5000 devices. RESULTS: A total of 475 patients were enrolled. The cohort was predominantly male (68.6%) with a median age of 49 years. Regression line slope estimates (ß) and linear correlation estimates (p) were as follows: CK.R (ß = 1.05, ρ = 0.9), CFF.MA (ß = 0.99, ρ = 0.95), CK.LY30 (ß = 1.01, ρ = 0.91), CRT.MA (TEG 6s) versus CK.MA (TEG 5000) (ß = 1.06, ρ = 0.86) as well as versus CRT.MA (TEG 5000) (ß = 0.93, ρ = 0.93), indicating strong reliability between the devices. Overall, within-device repeatability was better for TEG 6s versus TEG 5000, particularly for CFF.MA and CK.LY30. CONCLUSION: The TEG 6s device appears to be highly reliable for use in trauma patients, with close correlation to the TEG 5000 device and equivalent/improved within-device reliability. Given the potential advantages of using the TEG 6s device at the site of care, confirmation of agreement between the devices represents an important advance in diagnostic testing. LEVEL OF EVIDENCE: Diagnostic test, level II.


Assuntos
Transtornos da Coagulação Sanguínea/diagnóstico , Sistemas Automatizados de Assistência Junto ao Leito , Tromboelastografia/instrumentação , Ferimentos e Lesões/complicações , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Transtornos da Coagulação Sanguínea/sangue , Transtornos da Coagulação Sanguínea/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ferimentos e Lesões/sangue , Adulto Jovem
3.
J Surg Res ; 245: 610-618, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31522034

RESUMO

BACKGROUND: Herpes virus entry mediator (HVEM) is a coinhibitory molecule which can both stimulate and inhibit host immune responses. Altered expression of HVEM and its ligands is associated with increased nosocomial infections in septic patients. We hypothesize critically ill trauma patients will display increased lymphocyte HVEM expression and that such alteration is predictive of infectious events. MATERIALS AND METHODS: Trauma patients prospectively enrolled from the ICU were compared with healthy controls. Leukocytes were isolated from whole blood, stained for CD3 (lymphocytes) and HVEM, and evaluated by flow cytometry. Charts were reviewed for injuries sustained, APACHE II score, hospital course, and secondary infections. RESULTS: Trauma patients (n = 31) were older (46.7 ± 2.4 versus 36.8 ± 2.1 y; P = 0.03) than healthy controls (n = 10), but matched for male sex (74% versus 60%; P = 0.4). Trauma patients had higher presenting WBC (13.9 ± 1.3 versus 5.6 ± 0.5 × 106/mL; P = 0.002), lower percentage of CD3+ lymphocytes (7.5% ± 0.8 versus 22.5% ± 0.9; P < 0.001), but significantly greater expression of HVEM+/CD3+ lymphocytes (89.6% ± 1.46 versus 67.3% ± 1.7; P < 0.001). Among trauma patients, secondary infection during the hospitalization was associated with higher APACHE II scores (20.6 ± 1.6 versus 13.6 ± 1.4; P = 0.03) and markedly lower CD3+ lymphocyte HVEM expression (75% ± 2.6 versus 93% ± 0.7; P < 0.01). CONCLUSIONS: HVEM expression on CD3+ cells increases after trauma. Patients developing secondary infections have less circulating HVEM+CD3+. This implies HVEM signaling in lymphocytes plays a role in maintaining host defense to infection in after trauma. HVEM expression may represent a marker of infectious risk as well as a potential therapeutic target, modulating immune responses to trauma.


Assuntos
Tolerância Imunológica , Linfócitos/imunologia , Membro 14 de Receptores do Fator de Necrose Tumoral/metabolismo , Ferimentos e Lesões/imunologia , APACHE , Adulto , Biomarcadores/metabolismo , Complexo CD3/metabolismo , Estudos de Casos e Controles , Feminino , Voluntários Saudáveis , Humanos , /diagnóstico , Linfócitos/metabolismo , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Membro 14 de Receptores do Fator de Necrose Tumoral/imunologia , Ferimentos e Lesões/sangue , Ferimentos e Lesões/complicações
4.
J Vet Emerg Crit Care (San Antonio) ; 29(5): 521-527, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31482676

RESUMO

OBJECTIVE: To compare the prognostic value of admission hematologic parameters serum/plasma iron, red blood cell distribution width (RDW), and nucleated red blood cells (nRBCs) in dogs presenting with acute traumatic injury. DESIGN: Retrospective observational study (2009-2015). SETTING: University teaching hospital. ANIMALS: One hundred and twenty-nine clinical dogs presenting within 24 hours of acute traumatic injury. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: One hundred and twenty-nine dogs met the inclusion criteria and 109 (84.5%) survived, while 20 (15.5%) died or were euthanized in hospital. Patients with blunt force trauma comprised 79.8% of the patient population; dogs with penetrating trauma comprised 20.2% of cases. Hypoferremia occurred in all nonsurvivors, and the median serum/plasma iron concentration was significantly lower in nonsurvivors than survivors (P = 0.028). Normal or increased serum/plasma iron had 100% specificity and 100% positive predictive value for survival. Red blood cell distribution width was not significantly different between groups (P = 0.417). The presence of nRBCs was significantly associated with nonsurvival (P = 0.030), although the absolute nRBC concentrations were not significantly different (P = 0.070). A multiple logistic regression model found age, type of injury, presence of nRBCs, and serum/plasma iron to be independent predictors of survival with an area under the receiver operator characteristic curve of 0.813. CONCLUSIONS: The presence of nRBCs and low serum/plasma iron are associated with mortality in patients with acute trauma; however, red blood cell distribution width was not associated with survival. Absence of hypoferremia was highly associated with a favorable prognosis in this patient population. These parameters may warrant inclusion in trauma scoring systems.


Assuntos
Cães/lesões , Eritroblastos/fisiologia , Ferro/sangue , Ferimentos e Lesões/veterinária , Animais , Cães/sangue , Feminino , Escala de Gravidade do Ferimento , Modelos Logísticos , Masculino , Prognóstico , Curva ROC , Estudos Retrospectivos , Ferimentos e Lesões/sangue
5.
Surgery ; 166(6): 1122-1127, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31522748

RESUMO

BACKGROUND: Plasma thrombin generation has been used to characterize trauma-induced coagulopathy, but description of whole blood thrombin generation is lacking. This study aimed to evaluate plasma and whole blood thrombin generation in healthy volunteers and trauma patients. We hypothesized that (1) plasma and whole blood thrombin generation are distinct, (2) whole blood thrombin generation is more pronounced in trauma patients than in healthy volunteers, and (3) thrombin generation correlates with clinical coagulation assays. METHODS: Blood was collected from healthy volunteers and trauma patients at a single, level-1 trauma center. Whole blood thrombin generation was assessed with a prototype point-of-care whole blood thrombin generation device, and plasma thrombin generation was measured with a calibrated automated thrombogram analogue. Plasma and whole blood thrombin generation were compared and correlated with international normalized ratio and thrombelastography. RESULTS: Overall, 10 healthy volunteers (average age 30, 50% men) were included and 58 trauma patients (average age 34, 76% men, 55% blunt mechanism, and with a median new injury severity score of 17) were included. Plasma and whole blood thrombin generation differed with more robust thrombin generation in plasma. Trauma patients had a significantly increased whole blood thrombin generation compared with healthy volunteers]. Plasma thrombin generation correlated with international normalized ratio, whereas whole blood thrombin generation did not correlate with thrombelastography. CONCLUSION: Plasma and whole blood thrombin generation are distinct, highlighting the need to perform standardized assays to better understand their correlation and to assess how whole blood thrombin generation confers differential outcomes in trauma.


Assuntos
Transtornos da Coagulação Sanguínea/diagnóstico , Plasma/metabolismo , Trombina/metabolismo , Ferimentos e Lesões/complicações , Adulto , Transtornos da Coagulação Sanguínea/sangue , Transtornos da Coagulação Sanguínea/etiologia , Feminino , Voluntários Saudáveis , Humanos , Escala de Gravidade do Ferimento , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Tromboelastografia/métodos , Trombina/análise , Ferimentos e Lesões/sangue , Ferimentos e Lesões/diagnóstico
6.
J Trauma Acute Care Surg ; 87(2): 342-349, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31349348

RESUMO

BACKDROP: Clinicians intuitively recognize that faster time to hemostasis is important in bleeding trauma patients, but these times are rarely reported. METHODS: Prospectively collected data from the Pragmatic Randomized Optimal Platelet and Plasma Ratios trial were analyzed. Hemostasis was predefined as no intraoperative bleeding requiring intervention in the surgical field or resolution of contrast blush on interventional radiology (IR). Patients who underwent an emergent (within 90 minutes) operating room (OR) or IR procedure were included. Mixed-effects Poisson regression with robust error variance (controlling for age, Injury Severity Score, treatment arm, injury mechanism, base excess on admission [missing values estimated by multiple imputation], and time to OR/IR as fixed effects and study site as a random effect) with modified Bonferroni corrections tested the hypothesis that decreased time to hemostasis was associated with decreased mortality and decreased incidence of acute kidney injury (AKI), acute respiratory distress syndrome (ARDS), multiple-organ failure (MOF), sepsis, and venous thromboembolism. RESULTS: Of 680 enrolled patients, 468 (69%) underwent an emergent procedure. Patients with decreased time to hemostasis were less severely injured, had less deranged base excess on admission, and lower incidence of blunt trauma (all p < 0.05). In 408 (87%) patients in whom hemostasis was achieved, every 15-minute decrease in time to hemostasis was associated with decreased 30-day mortality (RR, 0.97; 95% confidence interval [CI], 0.94-0.99), AKI (RR, 0.97; 95% CI, 0.96-0.98), ARDS (RR, 0.98; 95% CI, 0.97-0.99), MOF (RR, 0.94; 95% CI, 0.91-0.97), and sepsis (RR, 0.98; 95% CI, 0.96-0.99), but not venous thromboembolism (RR, 0.99; 95% CI, 0.96-1.03). CONCLUSION: Earlier time to hemostasis was independently associated with decreased incidence of 30-day mortality, AKI, ARDS, MOF, and sepsis in bleeding trauma patients. Time to hemostasis should be considered as an endpoint in trauma studies and as a potential quality indicator. LEVEL OF EVIDENCE: Therapeutic/care management, level III.


Assuntos
Hemorragia/terapia , Técnicas Hemostáticas/mortalidade , Ferimentos e Lesões/terapia , Adulto , Hemorragia/sangue , Hemorragia/mortalidade , Humanos , Escala de Gravidade do Ferimento , Pessoa de Meia-Idade , Transfusão de Plaquetas/métodos , Distribuição de Poisson , Indicadores de Qualidade em Assistência à Saúde , Ressuscitação/métodos , Fatores de Tempo , Ferimentos e Lesões/sangue , Ferimentos e Lesões/mortalidade , Adulto Jovem
7.
J Trauma Acute Care Surg ; 87(2): 356-363, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31349349

RESUMO

BACKGROUND: The definition of massive transfusion (MT) in civilian pediatric trauma patients is not established. In combat-injured pediatric patients, the definition of MT is based on the volume of total blood products transfused. The aim of this study is to define MT in civilian pediatric trauma patients based on a packed red blood cell (PRBC) volume threshold and compare its predictive power to a total blood products volume threshold. METHODS: An analysis of the pediatric American College of Surgeons Trauma Quality Improvement Program database was performed (2014-2016) including pediatric trauma patients (4-18 years) who received blood products within 24 hours. Receiver operator characteristic curves for predicting mortality determined the optimal PRBC MT threshold. Area under receiver operating characteristic curve (AUROC) curve analysis was performed to compare the predictive power of a PRBC threshold to a total blood product threshold. RESULTS: A total of 1,495 patients were included. Sensitivity and specificity for 24-hour and in-hospital mortality were optimal at a PRBC threshold of 20 mL/kg. As compared with total blood products threshold, 20 mL/kg PRBCs volume achieved higher discriminatory power for predicting 24-hour (AUROC, 0.803 vs. 0.672; p < 0.001) and in-hospital mortality (AUROC, 0.815 vs. 0.686, p < 0.001). Patients who received an MT had higher Injury Severity Score (p < 0.001) and were more likely to receive mechanical ventilation (p < 0.001) and intensive care unit admission (p < 0.001). Overall 24-hour mortality (23.1% vs. 7.6%, p < 0.001) and in-hospital mortality (44.9% vs. 15.8%, p < 0.001) were higher in the MT group. On regression analysis, MT significantly predicted in-hospital mortality (odds ratio, 3.8 [2.9-4.9, 95% CI]) and 24-hour mortality (odds ratio, 3.3 [2.4-4.7, 95% CI]). CONCLUSION: The use of a PRBCs MT definition in civilian pediatric patients is a better predictor of mortality compared with total blood products threshold. These results provide a framework for MT protocol development. LEVEL OF EVIDENCE: Prognostic study, level III.


Assuntos
Hematócrito , Ressuscitação/mortalidade , Ferimentos e Lesões/terapia , Adolescente , Transfusão de Sangue , Criança , Pré-Escolar , Feminino , Hematócrito/métodos , Mortalidade Hospitalar , Humanos , Masculino , Valor Preditivo dos Testes , Curva ROC , Ressuscitação/métodos , Estudos Retrospectivos , Ferimentos e Lesões/sangue , Ferimentos e Lesões/mortalidade
8.
Surgery ; 166(3): 408-415, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31230841

RESUMO

BACKGROUND: Trauma patients with hypersensitivity to tissue plasminogen activator mediated fibrinolysis quantified by tissue plasminogen activator thromboelastography are at increased risk of massive transfusion. The tissue plasminogen activator thromboelastography assay has been tested in trauma patients using native thromboelastography with no exogenous activator. We hypothesize that adding an activator will expedite the time to results. METHODS: Healthy whole blood was assayed with and without exogenous plasmin, which acts to deplete inhibitors of fibrinolysis, mimicking trauma blood. Samples were assessed using native, kaolin, and rapid thromboelastography with and without tissue plasminogen activator. The tissue plasminogen activator thromboelastography indices of time to maximum amplitude and lysis at 30 minutes were contrasted between healthy blood with and without plasmin using the three different activators. The activators were then used with a tissue plasminogen activator thromboelastography in 100 trauma patients to assess performance in predicting massive transfusion. RESULTS: In healthy blood, regardless of activator, lysis at 30 minutes did not increase with plasmin alone, but did increase with tissue plasminogen activator (P = .012). Adding tissue plasminogen activator and plasmin increased lysis at 30 minutes (P = .036). Time to maximum amplitude was reduced with tissue plasminogen activator and plasmin compared with tissue plasminogen activator alone (P = .012). Activated thromboelastographies had increased lysis at 30 minutes (P = .002), but no difference in time to maximum amplitude compared with native thromboelastographies. In trauma patients, native tissue plasminogen activator thromboelastography had greater performance in predicting massive transfusion than activated tissue plasminogen activator thromboelastographies with no difference in time to maximum amplitude. CONCLUSION: Adding an activator to tissue plasminogen activator thromboelastography does not expedite time to maximum amplitude in healthy blood depleted of fibrinolysis inhibitors. Activated tissue plasminogen activator thromboelastographies are inferior to native tissue plasminogen activator thromboelastography for predicting massive transfusion and do not reduce the time to results.


Assuntos
Coagulação Sanguínea , Transfusão de Sangue , Tromboelastografia , Trombose/sangue , Trombose/diagnóstico , Ativador de Plasminogênio Tecidual , Ferimentos e Lesões/sangue , Ferimentos e Lesões/terapia , Adolescente , Adulto , Biomarcadores , Transfusão de Sangue/métodos , Viscosidade Sanguínea , Estudos de Casos e Controles , Gerenciamento Clínico , Feminino , Humanos , Masculino , Prognóstico , Ferimentos e Lesões/diagnóstico , Adulto Jovem
9.
Asia Pac J Clin Nutr ; 28(2): 411-418, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31192571

RESUMO

BACKGROUND AND OBJECTIVES: By combining the techniques of metabolomics and computational biology, this research aims to explore the mechanism of metabolic dynamics in critically injured patients and develop a new early warning method for mortality. METHODS AND STUDY DESIGN: A prospective cohort study was conducted, group plasma samples of critically injured patients were collected for 1H-NMR metabolomics analysis. The data was processed with partial least squares regression, to explore the role of enzyme-gene network regulatory mechanism in critically injured metabolic network regulation and to build a quantitative prediction model for early warning of fast death. RESULTS: In total, 60 patients were enrolled. There were significant differences in plasma metabolome between the surviving patients and the deceased ones. Compared to the surviving patients, 112 enzymes and genes regulating the 6 key metabolic marker disturbances of neopterin, corticosterone, 3-methylhistidine, homocysteine, Serine, tyrosine, prostaglandin E2, tryptophan, testosterone and estriol, were observed in the plasmas of deceased ones. Among patients of different injury stages, there were significant differences in plasma metabolome. Progressing from T0 to T50 stages of injury, increased levels of neopterin, corticosterone, prostaglandin E2, tryptophan and testosterone, together with decreased levels of homocysteine, and estriol, were observed. Eventually, the quantitative prediction model of death warning was established. Cross-validation results showed that the predictive effect was good (RMSE=0.18408, R2=0.87 p=0.036). CONCLUSIONS: Metabolomics approaches can be used to quantify the metabolic dynamics of patients with critically injuries and to predict death of critically injured patients by plasma 1H-NMR metabolomics.


Assuntos
Metaboloma/fisiologia , Metabolômica/métodos , Espectroscopia de Prótons por Ressonância Magnética/métodos , Ferimentos e Lesões/sangue , Ferimentos e Lesões/mortalidade , Adulto , Biomarcadores/sangue , Estudos de Coortes , Estado Terminal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
10.
Crit Care ; 23(1): 235, 2019 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-31253195

RESUMO

BACKGROUND: Necroptosis, a form of programmed cell death mediated by receptor interacting serine/threonine-protein kinase-3 (RIPK3), is implicated in murine models of acute respiratory distress syndrome (ARDS). We hypothesized that plasma RIPK3 concentrations in sepsis and trauma would be associated with ARDS development and that plasma RIPK3 would reflect changes in lung tissue RIPK3 in a murine model of systemic inflammation. METHODS: We utilized prospective cohort studies of critically ill sepsis (n = 120) and trauma (n = 180) patients and measured plasma RIPK3 at presentation and 48 h. Patients were followed for 6 days for ARDS by the Berlin definition. We used multivariable logistic regression to determine the association of plasma RIPK3 with ARDS in each cohort, adjusting for confounders. In mice, we determined whether plasma and lung tissue RIPK3 levels rise concomitantly 4 h after injection with lipopolysaccharide and ZVAD-FMK, an apoptosis inhibitor. RESULTS: The change in plasma RIPK3 from presentation to 48 h (ΔRIPK3) was associated with ARDS in sepsis (OR 1.30, 95% CI 1.03-1.63, per ½ standard deviation) and trauma (OR 1.79, 95% CI 1.33-2.40). This association was not evident for presentation RIPK3 levels. Secondary analyses showed similar findings for the association of ΔRIPK3 with acute kidney injury and 30-day mortality. Mice injected with lipopolysaccharide and ZVAD-FMK had significantly higher plasma (p < 0.001) and lung (p = 0.005) RIPK3 than control mice. CONCLUSIONS: The change in plasma RIPK3 from presentation to 48 h in both sepsis and trauma patients is independently associated with ARDS, and plasma RIPK3 may reflect RIPK3 activity in lung tissue.


Assuntos
Proteína Serina-Treonina Quinases de Interação com Receptores/análise , Síndrome do Desconforto Respiratório do Adulto/etiologia , Sepse/complicações , Ferimentos e Lesões/complicações , Adulto , Idoso , Biomarcadores/análise , Biomarcadores/sangue , Estudos de Coortes , Estado Terminal , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Proteína Serina-Treonina Quinases de Interação com Receptores/sangue , Síndrome do Desconforto Respiratório do Adulto/sangue , Síndrome do Desconforto Respiratório do Adulto/fisiopatologia , Sepse/sangue , Sepse/fisiopatologia , Índice de Gravidade de Doença , Ferimentos e Lesões/sangue , Ferimentos e Lesões/fisiopatologia
11.
Thromb Res ; 179: 56-63, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31078121

RESUMO

Wound healing is a complex process that consists of multiple phases, each of which are indispensable for adequate repair. Timely initiation and resolution of each of these phases namely, hemostasis, inflammation, proliferation and tissue remodeling, is critical for promoting healing and avoiding excess scar formation. While platelets have long been known to influence the healing process, other components of blood particularly coagulation factors and the fibrinolytic system also contribute to efficient wound repair. This review aims to summarize our current understanding of the role of platelets, the coagulation and fibrinolytic systems in cutaneous wound healing, with a focus on how these components communicate with immune and non-immune cells in the wound microenvironment. We also outline current and potential therapeutic strategies to improve the management of chronic, non-healing wounds.


Assuntos
Coagulação Sanguínea/fisiologia , Plaquetas/metabolismo , Cicatrização/fisiologia , Ferimentos e Lesões/sangue , Animais , Humanos , Camundongos
12.
J Trauma Acute Care Surg ; 87(3): 582-589, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31136528

RESUMO

BACKGROUND: Conventional coagulation assays (CCAs), prothrombin time (PT)/international normalized ratio (INR) and activated partial thromboplastin time (aPTT), detect clotting factor (CF) deficiencies in hematologic disorders. However, there is controversy about how these CCAs should be used to diagnose, treat, and monitor trauma-induced coagulopathy. Study objectives were to determine whether CCA abnormalities are reflective of deficiencies of coagulation factor activity in the setting of severe injury. METHODS: Patients without previous CF deficiency within a prospective database at an ACS-verified Level I trauma center had CF activity levels, PT/INR, aPTT, and fibrinogen levels measured upon emergency department arrival from 2014 to 2017. Linear regression assessed how CF activity explained the aPTT and PT/INR variation. Prolonged CCA values were set as INR greater than 1.3 and aPTT greater than 34 seconds. CF deficiency was defined as less than 30% activity, except for fibrinogen, defined as less than 150 mg/dL. RESULTS: Sixty patients with a mean age of 35.8 (SD, 13.6) years and median New Injury Severity Score of 32 (interquartile range, 12-43) were included; 53.3% sustained blunt injuries, 23.3% required massive transfusion, and mortality was 11.67%. Overall, 44.6% of the PT/INR variance and 49.5% of the aPTT variance remained unexplained by CF activity. Deficiencies of CFs were: common pathway, 25%; extrinsic pathway, 1.7%; and intrinsic pathway, 6.7%. The positive predictive value for CF deficiencies were: (1) PT/INR greater than 1.3:4.4% for extrinsic pathway, 56.5% for the common pathway; (2) aPTT greater than 34 seconds:16.7% for the intrinsic pathway, 73.7% for the common pathway. CONCLUSION: Almost half of the variances of PT/INR and aPTT were unexplained by CF activity. Prolonged PT/INR and aPTT were poor predictors of deficiencies in the intrinsic or extrinsic pathways; however, they were indicators of common pathway deficiencies. LEVEL OF EVIDENCE: Prognostic, level III.


Assuntos
Transtornos da Coagulação Sanguínea/etiologia , Ferimentos e Lesões/sangue , Adolescente , Adulto , Transtornos da Coagulação Sanguínea/sangue , Fatores de Coagulação Sanguínea/análise , Estudos de Casos e Controles , Criança , Transtornos de Proteínas de Coagulação/sangue , Transtornos de Proteínas de Coagulação/complicações , Fibrinogênio/análise , Humanos , Coeficiente Internacional Normatizado , Masculino , Tempo de Tromboplastina Parcial , Ferimentos e Lesões/complicações , Adulto Jovem
13.
Vet Comp Orthop Traumatol ; 32(4): 289-296, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31141824

RESUMO

OBJECTIVE: The aim of this study was to describe coagulation abnormalities and incidence of acute traumatic coagulopathy (ATC) in traumatized cats over the first 24 hours after admission. STUDY DESIGN: This was a prospective observational study at the university teaching hospital including 26 cats with acute (<5 hours) trauma. Blood was sampled for rotational thromboelastometry (ROTEM) parameters at presentation and 6 hours/24 hours thereafter. Rotational thromboelastometry tracings were defined as hypo- or hypercoagulable if ≥ 2 of the following parameters were above or below institutional reference intervals: clotting time, clot formation time (CFT), maximum clot firmness, maximum lysis or maximum clot elasticity. Hypocoagulability at presentation was defined as ATC. Injury severity scores, treatment and survival to hospital discharge were retrieved from patient records. RESULTS: The incidence of ATC was 15% and the most common ROTEM abnormalities in cats with ATC were clotting time and CFT prolongation in both extrinsic and intrinsic ROTEM profiles. After 24 hours, compared with presentation, significantly more cats were hypercoagulable (p = 0.047) and none of the cats showed hypocoagulopathy. Cats with ATC received significantly more blood transfusions (p = 0.008). CONCLUSION: The incidence of ATC in cats is higher than previously reported. Clotting time and CFT prolongations seem to be more common than hyperfibrinolysis and 53% of the cats became hypercoagulable within 24 hours. While the clinical relevance of ATC in cats needs to be investigated, cats diagnosed with ATC required significantly more blood transfusions.


Assuntos
Transtornos da Coagulação Sanguínea/veterinária , Doenças do Gato/sangue , Gatos/sangue , Gatos/lesões , Tromboelastografia/veterinária , Animais , Transtornos da Coagulação Sanguínea/sangue , Transtornos da Coagulação Sanguínea/epidemiologia , Transtornos da Coagulação Sanguínea/etiologia , Doenças do Gato/epidemiologia , Doenças do Gato/etiologia , Feminino , Hemostasia , Incidência , Masculino , Estudos Prospectivos , Ferimentos e Lesões/sangue , Ferimentos e Lesões/veterinária
14.
Ann Surg ; 269(6): 1184-1191, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31082919

RESUMO

OBJECTIVE: To determine the characteristics of trauma patients with low levels of fibrinolysis as detected by viscoelastic hemostatic assay (VHA) and explore the underlying mechanisms of this subtype. BACKGROUND: Hyperfibrinolysis is a central component of acute traumatic coagulopathy but a group of patients present with low levels of VHA-detected fibrinolysis. There is concern that these patients may be at risk of thrombosis if empirically administered an antifibrinolytic agent. METHODS: A prospective multicenter observational cohort study was conducted at 5 European major trauma centers. Blood was drawn on arrival, within 2 hours of injury, for VHA (rotation thromboelastometry [ROTEM]) and fibrinolysis plasma protein analysis including the fibrinolytic mediator S100A10. An outcomes-based threshold for ROTEM hypofibrinolysis was determined and patients grouped by this and by D-dimer (DD) levels. RESULTS: Nine hundred fourteen patients were included in the study. The VHA maximum lysis (ML) lower threshold was determined to be <5%. Heterogeneity existed among patients with low ML, with survivors sharing similar clinical and injury characteristics to patients with normal ML values (5-15%). Those who died were critically injured with a preponderance of traumatic brain injury and had a 7-fold higher DD level (died vs. survived: 103,170 vs. 13,672 ng/mL, P < 0.001). Patients with low ML and high DD demonstrated a hyperfibrinolytic biomarker profile, low tissue plasminogen activator levels but high plasma levels of S100A10. S100A10 was negatively correlated with %ML (r = -0.26, P < 0.001) and caused a significant reduction in %ML when added to whole blood ex-vivo. CONCLUSIONS: Patients presenting with low ML and low DD levels have low injury severity and normal outcomes. Conversely, patients with low ML but high DD levels are severely injured, functionally coagulopathic and have poor clinical outcomes. These patients have low tissue plasminogen activator levels and are not detectable by ROTEM. S100A10 is a cell surface plasminogen receptor which may drive the hyperfibrinolysis in these patients and which when shed artificially lowers %ML ex-vivo.


Assuntos
Anexina A2/sangue , Fibrinólise/fisiologia , Proteínas S100/sangue , Ferimentos e Lesões/sangue , Ferimentos e Lesões/complicações , Adulto , Idoso , Fatores de Coagulação Sanguínea/metabolismo , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Taxa de Sobrevida , Tromboelastografia , Ferimentos e Lesões/mortalidade , Adulto Jovem
16.
J Trauma Acute Care Surg ; 87(1): 49-53, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31033893

RESUMO

BACKGROUND: Recent data demonstrate the safety of uncrossmatched cold-stored whole blood (WB) transfusion in pediatric trauma patients. The hemostatic capabilities of platelets within the cold-stored WB unit have been demonstrated via in vitro studies and animal models. However, platelet function has not been evaluated in pediatric recipients of cold-stored WB transfusions. METHODS: Injured children, 2 years or older and 10 kg or greater with hemorrhagic shock received up to 30 mL/kg of cold-stored, low titer (<50) anti-A and -B, leukoreduced, group O- WB during their initial resuscitation. Patients were included if (1) they received WB and no conventional platelets, and (2) platelet count and thromboelastography maximum amplitude were measured both before and after transfusion. These data and relevant clinical outcomes (mortality, intensive care unit length of stay [LOS], hospital LOS and ventilator days) were compared to a historical cohort of pediatric trauma patients who received uncrossmatched red blood cells (RBC) and conventional room temperature platelets. RESULTS: Twenty-two children were included in the study; 14 in the component cohort versus 8 in the WB cohort. Neither posttransfusion platelet count (129 × 109/L vs. 135 × 109/L) nor function (thromboelastography maximum amplitude, 59.5 mm vs. 60.2 mm) differed significantly between children receiving cold-stored platelets within the WB unit versus children who received conventional warm platelets. Median (interquartile range) weight-adjusted platelet transfusion volume in the historical cohort was 4.6 (2.5-7.7) mL/kg vs. 2.4 (1.3-4.0) mL/kg in the WB cohort (p = 0.03). There was no difference between groups in age, race, mechanism of injury, Injury Severity Score, vital signs, and severe traumatic brain injury (TBI). Outcomes, including mortality, intensive care unit LOS, hospital LOS, and ventilator days, were not significantly different between groups. CONCLUSION: No difference was seen in posttransfusion platelet number or function in severely injured children receiving cold-stored WB platelets as compared to those receiving conventional room temperature-stored platelets. Larger cohorts are required to confirm these findings. LEVEL OF EVIDENCE: Therapeutic, level IV.


Assuntos
Plaquetas/fisiologia , Preservação de Sangue , Transfusão de Sangue , Choque Hemorrágico/terapia , Ferimentos e Lesões/terapia , Adolescente , Preservação de Sangue/métodos , Transfusão de Sangue/métodos , Criança , Pré-Escolar , Feminino , Humanos , Tempo de Internação/estatística & dados numéricos , Masculino , Contagem de Plaquetas , Refrigeração , Choque Hemorrágico/sangue , Ferimentos e Lesões/sangue
17.
Colloids Surf B Biointerfaces ; 179: 17-27, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-30928801

RESUMO

Antimicrobial resistance is becoming more and more serious and has become a potential hazard to human life and health. The fabrication of some new antibacterial substances against resistant bacteria is demanded. With the wide application and research of carbon nanomaterials, nitrogen-doped carbon quantum dots (NCQDs) were synthesized by a one-step chemical route herein. The particle size of NCQDs in the range of 2-5 nm were characterized by transmission electron microscopy (TEM), atomic force microscopy, and dynamic light scattering. The functional groups and optical properties of NCQDs were investigated by UV-vis absorption spectroscopy, X-ray photoelectron spectroscopy and Fourier transform infrared spectroscopy. Disk-diffusion tests showed that the NCQDs had specific antibacterial activity against Staphylococcus. TEM showed that the NCQDs could destroy the cell structure of Staphylococcus aureus and methicillin-resistant Staphylococcus aureus (MRSA) but could not combat Escherichia coli. The antibacterial mechanism may be that positively charged NCQDs firstly interacted with the negatively charged bacteria, and then specifically anchored on some specific sites on the surface of Staphylococcus. The NCQDs were applied to treat wounds infected with MRSA and showed the same therapeutic effect as vancomycin. Photomicrographs of hematoxylin-eosin-stained histological sections showed that the NCQDs at concentrations effectively killing S. aureus and MRSA caused negligible toxicity to the main rat organs, including heart, liver, spleen, lung, and kidney. Thus, the NCQDs can be developed as a promising antibacterial agent for Staphylococcus. And the NCQDs are likely to treat local infections caused by Staphylococcus clinically, especially S. aureus and MRSA.


Assuntos
Antibacterianos/uso terapêutico , Carbono/química , Nitrogênio/química , Pontos Quânticos/química , Staphylococcus aureus/efeitos dos fármacos , Ferimentos e Lesões/tratamento farmacológico , Ferimentos e Lesões/microbiologia , Animais , Antibacterianos/farmacologia , Proteína C-Reativa/metabolismo , Escherichia coli/efeitos dos fármacos , Células HeLa , Humanos , Contagem de Leucócitos , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Espectroscopia Fotoeletrônica , Pontos Quânticos/ultraestrutura , Ratos Sprague-Dawley , Testes de Toxicidade , Cicatrização/efeitos dos fármacos , Ferimentos e Lesões/sangue
18.
Transfusion ; 59(S2): 1467-1473, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30980736

RESUMO

BACKGROUND: Platelet (PLT) transfusion is a widely used therapy in treating or preventing bleeding and hemorrhage in patients with thrombocytopenia or trauma. Compared to the relative ease of PLT transfusion, current practice for PLT storage at room temperature (RT) for up to 5 to 7 days is inefficient, costly, wasteful, and relatively unsafe. STUDY DESIGN AND METHODS: This study was a review of major advances in PLT derivative products with improved hemostatic potential and safety feature. RESULTS: Recent progress in understanding the PLT activation and host clearance mechanisms has led to reassessments of current and new storage conditions that employ refrigeration and/or cryopreservation to overcome storage lesions and significantly extend shelf life of PLTs with reduced risk of pathogen contamination. DISCUSSION: It is anticipated that future PLT preservation involving cold, frozen, and/or pathogen reduction strategies in proper PLT additive solutions will enable longer term and safer PLT storage.


Assuntos
Plaquetas , Preservação de Sangue , Segurança do Sangue , Criopreservação , Transfusão de Plaquetas , Coagulação Sanguínea , Preservação de Sangue/métodos , Preservação de Sangue/tendências , Segurança do Sangue/métodos , Segurança do Sangue/tendências , Criopreservação/métodos , Criopreservação/tendências , Hemorragia/sangue , Hemorragia/terapia , Humanos , Transfusão de Plaquetas/métodos , Transfusão de Plaquetas/tendências , Trombocitopenia/sangue , Trombocitopenia/terapia , Ferimentos e Lesões/sangue , Ferimentos e Lesões/terapia
19.
Transfusion ; 59(S2): 1601-1607, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30980751

RESUMO

BACKGROUND: Hemorrhage is the leading cause of preventable trauma-related mortality and is frequently aggravated by acute traumatic coagulopathy (ATC). Viscoelastic tests such as rotational thromboelastometry (ROTEM) may improve identification and management of ATC. This study aimed to prospectively evaluate changes in ROTEM among combat casualties during the first 24 hours and compare the capabilities of our conventional clotting assay (international normalized ratio [INR], >1.2) to a proposed integrated ROTEM model (INR >1.2 with the addition of tissue factor pathway activation thromboelastometry [EXTEM] A5 ≤35 mm and/or EXTEM LI30 <97% on admission) to identify ATC and predict massive transfusion (MT). STUDY DESIGN AND METHODS: This was a prospective observational study of trauma patients treated in NATO hospitals in Afghanistan between January 2012 and June 2013. ROTEM (EXTEM, functional fibrinogen thromboelastometry, APTEM, EXTEM with the addition of a fibrinolysis inhibitor) was performed on admission and at 6 and 24 hours by a designated research team. Treatment teams did not have access to the ROTEM results. RESULTS: ROTEM values were available for 40 male casualties. The integrated ROTEM model classified 15% more patients with ATC than with INR alone and increased the detection of those that required MT by 22%. The sensitivity of the integrated ROTEM model to predict MT was higher than with INR greater than 1.2 (86% vs. 64%); however, specificity with both definitions for predicting MT was poor (38% vs. 50%, respectively). CONCLUSION: These observations support the importance of early identification of and intervention in ATC. Integrating ROTEM into the definition of ATC would increase detection of those requiring MT arguing for its use as an adjunct to clinical presentation in the ultimate decision to initiate MT.


Assuntos
Transtornos da Coagulação Sanguínea , Tomada de Decisão Clínica , Hemorragia , Coeficiente Internacional Normatizado , Modelos Biológicos , Tromboelastografia , Ferimentos e Lesões , Adolescente , Adulto , Campanha Afegã de 2001- , Afeganistão , Transtornos da Coagulação Sanguínea/sangue , Transtornos da Coagulação Sanguínea/terapia , Hemorragia/sangue , Hemorragia/terapia , Hospitais Militares , Humanos , Masculino , Militares , Valor Preditivo dos Testes , Estudos Prospectivos , Ferimentos e Lesões/sangue , Ferimentos e Lesões/terapia
20.
Med Leg J ; 87(2): 67-73, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30968747

RESUMO

Literature on electrocution in Italy is limited. The authors have focused their attention on the use of scanning electron microscope/energy-dispersive X-ray analysis in order to evaluate the current mark even on paraffin-embedded samples. A total of 24,104 autopsies were performed at the Section of Legal Medicine of Milan (1993-2017); all cases of death caused by electrocution (low and high voltage) were selected. We assessed a regular histological examination, a toxicological examination and detected metallisation with energy-dispersive X-ray spectroscopy analysis on paraffin-embedded tissues of typical current marks. We collected 27 high-voltage fatalities and five cases of low-voltage suicide electrocution; the technique revealed itself as sensitive. In all cases, microscopic examination highlighted the typical signs of electric current and thermal damage but the histochemical specific stainings for copper and iron gave negative results. Scanning electron microscope/energy-dispersive X-ray analysis, assessed on these same samples, even when paraffin-embedded, however, enabled us to detect these elements and differentiate between the various metal residues involved in the electrocution process. Based on their experience, authors advise the use of scanning electron microscope/energy-dispersive X-ray analysis on electrocution deaths to provide information for forensic diagnosis.


Assuntos
Traumatismos por Eletricidade/mortalidade , Suicídio/tendências , Ferimentos e Lesões/fisiopatologia , Adolescente , Adulto , Traumatismos por Eletricidade/sangue , Traumatismos por Eletricidade/fisiopatologia , Feminino , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Inclusão em Parafina/métodos , Análise Espectral/métodos , Ferimentos e Lesões/sangue , Ferimentos e Lesões/complicações
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