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1.
Clin Biochem ; 75: 78-82, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31770522

RESUMO

BACKGROUND: Till date, China has not issued industry standards for reference intervals (RIs) of pediatric blood coagulation indices. Here, we evaluated changes in the coagulation indices in the venous blood of healthy children aged 29 days to 12 years derived using the ACL Top 700 system and established appropriate RIs. METHODS: We analyzed venous blood from 1770 healthy children for five coagulation indices. RIs were established according to the Clinical and Laboratory Standards Institute C28-A3c guideline. RESULTS: The coagulation indices were grouped by age. For prothrombin time (PT) and international normalization ratio (INR), the RIs of infants and toddlers were identical; preschool children had the same RI as school-age children. Pediatric RIs for PT and INR were slightly lower than those for adults. The RIs of activated partial thromboplastin time (APTT), thrombin time (TT), and fibrinogen (FIB) in childhood were divided into two groups by age (1 month to 1 year and 1-12 years). The RI of APTT in infants was the widest; the overall level of FIB in infants was the lowest; children's APTT and FIB RIs were lower than those of adults. The pattern of TT values and RI trends in childhood were similar to those of APTT. CONCLUSIONS: There were minor changes in the RIs of coagulation indices for children. The RIs of PT, INR, APTT, TT, and FIB must be grouped by age. The RIs of coagulation indices for children were different from those for adults; therefore, establishing separate RIs for children is necessary.


Assuntos
Testes de Coagulação Sanguínea/normas , Coagulação Sanguínea/fisiologia , Criança , Pré-Escolar , China/epidemiologia , Feminino , Voluntários Saudáveis , Humanos , Lactente , Recém-Nascido , Masculino , Valores de Referência
2.
Immunity ; 51(6): 983-996.e6, 2019 12 17.
Artigo em Inglês | MEDLINE | ID: mdl-31836429

RESUMO

Excessive activation of the coagulation system leads to life-threatening disseminated intravascular coagulation (DIC). Here, we examined the mechanisms underlying the activation of coagulation by lipopolysaccharide (LPS), the major cell-wall component of Gram-negative bacteria. We found that caspase-11, a cytosolic LPS receptor, activated the coagulation cascade. Caspase-11 enhanced the activation of tissue factor (TF), an initiator of coagulation, through triggering the formation of gasdermin D (GSDMD) pores and subsequent phosphatidylserine exposure, in a manner independent of cell death. GSDMD pores mediated calcium influx, which induced phosphatidylserine exposure through transmembrane protein 16F, a calcium-dependent phospholipid scramblase. Deletion of Casp11, ablation of Gsdmd, or neutralization of phosphatidylserine or TF prevented LPS-induced DIC. In septic patients, plasma concentrations of interleukin (IL)-1α and IL-1ß, biomarkers of GSDMD activation, correlated with phosphatidylserine exposure in peripheral leukocytes and DIC scores. Our findings mechanistically link immune recognition of LPS to coagulation, with implications for the treatment of DIC.


Assuntos
Caspases Iniciadoras/metabolismo , Coagulação Intravascular Disseminada/patologia , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Lipopolissacarídeos/metabolismo , Proteínas de Ligação a Fosfato/metabolismo , Fosfatidilserinas/metabolismo , Tromboplastina/metabolismo , Animais , Coagulação Sanguínea/fisiologia , Caspases Iniciadoras/genética , Linhagem Celular Tumoral , Endotoxemia/patologia , Ativação Enzimática , Células HT29 , Células HeLa , Humanos , Interleucina-1alfa/sangue , Interleucina-1beta/sangue , Peptídeos e Proteínas de Sinalização Intracelular/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteínas de Ligação a Fosfato/genética , Piroptose/fisiologia , Transdução de Sinais/fisiologia
3.
Infect Immun ; 87(12)2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31548314

RESUMO

Leptospirosis is one of the most widespread zoonoses caused by pathogenic Leptospira spp. In this study, we report that the LIC11966/ErpY-like lipoprotein is a surface-exposed outer membrane protein exclusively present in pathogenic species of Leptospira The recombinant ErpY (rErpY)-like protein is recognized by the immunoglobulins of confirmed leptospirosis sera of diverse hosts (human, bovine, and canine), suggesting the expression of the native leptospiral surface protein during infection. Circular dichroism of pure rErpY-like protein showed the secondary structural integrity to be uncompromised during the purification process. Analysis of the rErpY-like protein by native polyacrylamide gel electrophoresis, chemical cross-linking, dynamic light scattering, and field emission transmission electron microscopy demonstrated it undergoes supramolecular assembly. The rErpY-like protein can bind to diverse host extracellular matrices, and it presented a saturable and strong binding affinity (dissociation constant [KD ] of 70.45 ± 4.13 nM) to fibrinogen, a central host plasma component involved in blood clotting. In the presence of the rErpY-like supramolecule, thrombin-catalyzed fibrin clot formation is inhibited up to 7%, implying its role in inhibiting blood coagulation during Leptospira infection. In addition, binding of the rErpY-like supramolecule to complement factors H and I suggests the protein also contributes to Leptospira evading innate host defense during infection by inactivating alternative complement pathways. This study reveals that rErpY-like protein is functionally active in the supramolecular state and performs moonlighting activity under the given in vitro conditions.


Assuntos
Proteínas da Membrana Bacteriana Externa/metabolismo , Coagulação Sanguínea/fisiologia , Fator H do Complemento/metabolismo , Fator I do Complemento/metabolismo , Leptospira/imunologia , Leptospirose/diagnóstico , Animais , Dicroísmo Circular , Via Alternativa do Complemento/imunologia , Feminino , Tempo de Lise do Coágulo de Fibrina , Lipoproteínas/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Ligação Proteica , Estrutura Secundária de Proteína , Trombina/metabolismo
4.
Clin Lab ; 65(8)2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31414765

RESUMO

BACKGROUND: Collective specific variegated alterations in the hemostatic system cast doubt on the uncritical usage of standard hemotherapy algorithms in patients with chronic liver disease. The aims of the present study were to examine the applicability of commonly used early viscoelastic parameters in this particular collective and to develop first-time thresholds for the early detection of clinically relevant platelet dysfunction. METHODS: Patients suffering from advanced chronic liver disease were enrolled in this prospective single-centre study and consecutively allocated to Group 1 (MELD (Model for End-Stage Liver Disease) score 6 - 11) or Group 2 (MELD score > 16). We performed conventional laboratory coagulation analyses, as well as viscoelastometry (ROTEM®, EXTEM test, and FIBTEM test) and aggregometry (Multiplate®, ASPItest, and ADPtest), in each patient to analyze their hemostatic capacity. We analyzed the association between the A10 values (clot firmness 10 minutes after the initiation of clot building) in the EXTEM and FIBTEM tests and the corresponding Maximum Clot Firmness (MCF) values and performed receiver operating characteristic (ROC) curve analyses to investigate the ability of early parameters from the ASPItest and ADPtest (Aggregation Units (AU) 1 minute (T1), 2 minutes (T2) and 3 minutes (T3) after induction of platelet aggregation) of the Multiplate® system to predict clinically relevant platelet dysfunction. RESULTS: In the complete study collective (n = 50) and in Group 1 and Group 2 (each n = 25), A10 values correlated highly significantly with corresponding MCF values. The bias between the A10 and the MCF values was 5.1 ± 2.4 mm and 1.2 ± 1.1 mm for the EXTEM test and FIBTEM test, respectively. The highest sensitivity and specificity values for the prediction of clinically relevant platelet dysfunction at measuring point T3 were analyzed to be the values 54.9 AU/min in the ASPItest and 50.1 AU/min in the ADPtest. CONCLUSIONS: The results of the study indicate that the basic principle of using the A10 values as so-called early vis-coelastic parameters for the estimation of MCF values is legitimate. The presumably divergent bias between the A10 and MCF values necessitates the development of collective specific thresholds in hemotherapy algorithms for coagulopathic patients suffering from advanced chronic liver disease.


Assuntos
Coagulação Sanguínea/fisiologia , Plaquetas/fisiologia , Hepatopatias/sangue , Agregação Plaquetária/fisiologia , Tromboelastografia/métodos , Idoso , Testes de Coagulação Sanguínea/métodos , Plaquetas/metabolismo , Viscosidade Sanguínea/fisiologia , Doença Crônica , Feminino , Humanos , Hepatopatias/diagnóstico , Hepatopatias/fisiopatologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Curva ROC
5.
PLoS Comput Biol ; 15(8): e1007266, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31381558

RESUMO

During thrombosis, thrombin generates fibrin, however fibrin reversibly binds thrombin with low affinity E-domain sites (KD = 2.8 µM) and high affinity γ'-fibrin sites (KD = 0.1 µM). For blood clotting on collagen/tissue factor (1 TF-molecule/µm2) at 200 s-1 wall shear rate, high µM-levels of intraclot thrombin suggest robust prothrombin penetration into clots. Setting intraclot zymogen concentrations to plasma levels (and neglecting cofactor rate limitations) allowed the linearization of 7 Michaelis-Menton reactions between 6 species to simulate intraclot generation of: Factors FXa (via TF/VIIa or FIXa), FIXa (via TF/FVIIa or FXIa), thrombin, fibrin, and FXIa. This reduced model [7 rates, 2 KD's, enzyme half-lives~1 min] predicted the measured clot elution rate of thrombin-antithrombin (TAT) and fragment F1.2 in the presence and absence of the fibrin inhibitor Gly-Pro-Arg-Pro. To predict intraclot fibrin reaching 30 mg/mL by 15 min, the model required fibrinogen penetration into the clot to be strongly diffusion-limited (actual rate/ideal rate = 0.05). The model required free thrombin in the clot (~100 nM) to have an elution half-life of ~2 sec, consistent with measured albumin elution, with most thrombin (>99%) being fibrin-bound. Thrombin-feedback activation of FXIa became prominent and reached 5 pM FXIa at >500 sec in the simulation, consistent with anti-FXIa experiments. In predicting intrathrombus thrombin and fibrin during 15-min microfluidic experiments, the model revealed "cascade amplification" from 30 pM levels of intrinsic tenase to 15 nM prothrombinase to 15 µM thrombin to 90 µM fibrin. Especially useful for multiscale simulation, this reduced model predicts thrombin and fibrin co-regulation during thrombosis under flow.


Assuntos
Coagulação Sanguínea/fisiologia , Modelos Biológicos , Trombose/sangue , Plaquetas/metabolismo , Colágeno/sangue , Biologia Computacional , Simulação por Computador , Cisteína Endopeptidases/sangue , Fator XIa/metabolismo , Fibrina/metabolismo , Humanos , Técnicas In Vitro , Cinética , Proteínas de Neoplasias/sangue , Fluxo Sanguíneo Regional/fisiologia , Trombina/metabolismo , Tromboplastina/metabolismo
6.
Ann Biol Clin (Paris) ; 77(4): 447-452, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31339492

RESUMO

The complement system is composed of a set of plasma or membrane proteins. Complement protein deficiencies can be inherited or acquired, through the presence of autoantibodies or through consumption. We evaluated the analytical performance of the Optilite® analyser for the determination of the C3 and C4 levels and for the evaluation of the total complement activity. The intra- and inter-series CVs were evaluated and have showed satisfactory results, the concordances with analysers currently used in the laboratory (BNII® and BCT®, Siemens) are very good, as is the agreement between the serum and plasma samples. We also determined the reference values for the different parameters tested in view of a routine use of Optilite® analyser in the laboratory.


Assuntos
Complemento C3/análise , Complemento C4/análise , Proteínas do Sistema Complemento/análise , Testes Hematológicos/instrumentação , Adulto , Artefatos , Automação Laboratorial/instrumentação , Automação Laboratorial/normas , Análise Química do Sangue/instrumentação , Análise Química do Sangue/métodos , Análise Química do Sangue/normas , Coagulação Sanguínea/fisiologia , Complemento C3/metabolismo , Complemento C4/metabolismo , Proteínas do Sistema Complemento/metabolismo , Contaminação de Equipamentos , Testes Hematológicos/métodos , Testes Hematológicos/normas , Humanos , Padrões de Referência , Reprodutibilidade dos Testes
7.
Cancer Treat Res ; 179: 11-36, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31317478

RESUMO

Thrombosis is a major cause of morbidity and mortality in cancer patients. The pathogenesis of blood coagulation activation in oncological patients is complex and involves both clinical and biological factors. Abnormalities in one or more coagulation test are common in cancer patients, even without thrombotic manifestations, indicating an ongoing hypercoagulable condition. Moreover, venous thromboembolism (VTE) can be the first symptom of an occult malignancy in an otherwise healthy individual. The levels of laboratory markers of activation of blood coagulation parallel the development of malignancy, being the coagulant mechanisms important for both thrombogenesis and tumor progression. Besides general clinical risk factors for VTE, also disease-specific clinical factors, i.e., type and stage of the tumor, and anticancer therapies increase the thrombotic risk in these patients. Furthermore, biological factors, including the cancer cell-specific prothrombotic properties together with the host cell inflammatory response to the tumor, are relevant as well as unique players in the pathogenesis of the cancer-associated hypercoagulability. Cancer cells produce and release procoagulant and fibrinolytic proteins, inflammatory cytokines, and procoagulant microparticles. They also express adhesion molecules binding to the receptors of host vascular cells (i.e., endothelial cells, platelets, and leukocytes), thereby stimulating the prothrombotic properties of these normal cells, including the shed of cell-specific microparticles and neutrophil extracellular traps. Of interest, several genes responsible for the cellular neoplastic transformation drive the programs of hemostatic properties expressed by cancer tissues. A better understanding of such mechanisms will help the development of novel strategies to prevent and treat the Trousseau's syndrome (i.e., cancer-associated thrombosis).


Assuntos
Neoplasias/fisiopatologia , Trombose/fisiopatologia , Coagulação Sanguínea/fisiologia , Humanos , Neoplasias/complicações , Trombose/etiologia
8.
Braz J Cardiovasc Surg ; 34(3): 327-334, 2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-31310472

RESUMO

OBJECTIVE: The main goal of our study was to assess the impact of vascular procedures on the activity of hemostatic and fibrinolytic pathways. METHODS: We enrolled 38 patients with ≥ 45 years old undergoing surgery for abdominal aortic aneurysm or peripheral artery disease under general or regional anesthesia and who were hospitalized at least one night after the procedure. Patients undergoing carotid artery surgery and those who had acute bypass graft thrombosis, cancer, renal failure defined as estimated glomerular filtration rate < 30 ml/min/1.73m2, venous thromboembolism three months prior to surgery, or acute infection were excluded from the study. We measured levels of markers of hemostasis (factor VIII, von Willebrand factor:ristocetin cofactor [vWF:CoR], antithrombin), fibrinolysis (D-dimer, tissue plasminogen activator [tPA], plasmin-antiplasmin complexes), and soluble cluster of differentiation 40 ligand (sCD40L) before and 6-12h after vascular procedure. RESULTS: Significant differences between preoperative and postoperative levels of factor VIII (158.0 vs. 103.3, P<0.001), antithrombin (92.1 vs. 74.8, P<0.001), D-dimer (938.0 vs. 2406.0, P=0.005), tPA (10.1 vs. 12.8, P=0.002), and sCD40L (9092.9 vs. 1249.6, P<0.001) were observed. There were no significant differences between pre- and postoperative levels of vWF:CoR (140.6 vs. 162.8, P=0.17) and plasmin-antiplasmin complexes (749.6 vs. 863.7, P=0.21). CONCLUSION: Vascular surgery leads to significant alterations in hemostatic and fibrinolytic systems. However, the direction of these changes in both pathways remains unclear and seems to be different depending on the type of surgery. A study utilizing dynamic methods of coagulation and fibrinolysis assessment performed on a larger population is warranted.


Assuntos
Aneurisma da Aorta Abdominal/cirurgia , Coagulação Sanguínea/fisiologia , Fibrinólise/fisiologia , Doença Arterial Periférica/cirurgia , Procedimentos Cirúrgicos Vasculares/efeitos adversos , Idoso , Biomarcadores/sangue , Fatores de Coagulação Sanguínea/análise , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Período Pós-Operatório , Período Pré-Operatório , Valores de Referência , Fatores de Risco , Estatísticas não Paramétricas , Resultado do Tratamento
9.
Hypertens Pregnancy ; 38(3): 176-183, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31271326

RESUMO

Objective: We aimed to determine whether abnormal coagulation laboratory testing results in preeclampsia, are associated with adverse pregnancy outcomes and placental histopathology lesions. Methods: Demographic, labor, laboratory-testing, and placental histopathology reports of pregnancies complicated by preeclampsia were compared between those with and without abnormal coagulation profile (ACP). Results: Of 348 cases of preeclampsia 16.1% had ACP. There were no differences between the groups in GA at delivery, severe features, placental-abruption, SGA, composite adverse neonatal outcome and placental histopathology lesions. Conclusion: ACP in pregnancies complicated by preeclampsia was not associated with any of the studied outcomes. Our data question the usefulness of routine coagulation tests in the initial assessment of women presenting with preeclampsia.


Assuntos
Coagulação Sanguínea/fisiologia , Placenta/patologia , Pré-Eclâmpsia/sangue , Adulto , Testes de Coagulação Sanguínea , Feminino , Humanos , Recém-Nascido Pequeno para a Idade Gestacional , Pré-Eclâmpsia/patologia , Gravidez , Resultado da Gravidez , Adulto Jovem
10.
Forensic Sci Int ; 302: 109856, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31247451

RESUMO

The assessment and interpretation of the timing of skeletal trauma can be of extreme difficulty in post-mortem specimens, especially because of post-mortem processes and taphonomic events. The chronological diagnosis of bone trauma, consisting usually in the gross distinction between antemortem, perimortem and post-mortem, is based almost uniquely on macroscopic and morphologic parameters in the anthropological field. However, both the interference of taphonomy and the scarce persistence of specific features indicating vitality (meaning etymologically "produced in life") and/or some very early bone healing reactions, make it extremely difficult. In this perspective, it is important not only to distinguish between peri and post-mortem lesions, but also to interpret perimortem lesions with respect to vitality and time elapsed since the trauma which may change the course of the investigations. And techniques of forensic pathology applied to forensic anthropology can come in extremely handy. If any traces of vital blood extravasation, haemorrhage, hematoma, inflammation, and biomarkers of early healing reaction are found in the bone tissue of a skeletal lesion (regardless the state of preservation of the body), then can they be used as a diagnostic tool or marker of vitality for that lesion? In these terms, vital reactions like bleeding or any early sign of bone healing can be the only evidence for demonstrating that a traumatic event was prior the death. Nevertheless, very little information, or research for that matter, is available in literature concerning persistence and detectability of vitality markers during the bone decomposition process. A fundamental point for properly determining the vitality of a fracture and estimating the post-traumatic time interval in skeletal lesions is the physio-pathological picture of the very initial healing process. This article attempts to provide a review of the physiopathological current knowledge available and applicable to osteology.


Assuntos
Remodelação Óssea/fisiologia , Fraturas Ósseas/patologia , Osteogênese/fisiologia , Biomarcadores/metabolismo , Coagulação Sanguínea/fisiologia , Citocinas/fisiologia , Hematoma/patologia , Hemorragia/patologia , Humanos , Imuno-Histoquímica , Peptídeos e Proteínas de Sinalização Intercelular/fisiologia , Neovascularização Fisiológica/fisiologia , Osteoblastos/fisiologia , Osteoclastos/fisiologia
11.
Ann Biol Clin (Paris) ; 77(3): 272-280, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-31219420

RESUMO

The aim of this study is to evaluate the anomalies of coagulation (by assaying the factor VIII, fibrinogen, D-dimer and resistance to activated protein C) in patients with lung cancer. METHODS: 101 patients newly diagnosed with lung cancer before treatment and 72 control blood donors were included in the study after informed consent. All coagulation tests were performed on Stago STA-Compact. Statistical analyses were performed using the SPSS software version 22. RESULTS: The study of the coagulation showed that plasma levels of all coagulation parameters were significantly higher in patients compared to controls. Coagulation was not influenced by the age of patients. No significant difference was found between the histological types in terms of coagulation. Factor VIII level was significantly elevated in stage IV patients compared to stage I + II + III patients. At the cut-off value of 6.22 g/L, the elevation of fibrinogen had a significant statistical relationship with thromboembolic disease (p=0.014) giving an hazard ratio of 3.868, confidence interval [1.358-11.012]. In multivariate analysis the hazard ratio doubled to 6.398, confidence interval [1,970-20,778]. DISCUSSION: Lung cancer patients showed an increase in coagulation factors that resulted in a state of hypercoagulability that was independent of the histology of lung cancer. The elevation of fibrinogen was predictive of thromboembolic disease at the early diagnosis of lung cancer before any therapy.


Assuntos
Adenocarcinoma de Pulmão/sangue , Carcinoma Pulmonar de Células não Pequenas/sangue , Neoplasias Pulmonares/sangue , Ativação Plaquetária/fisiologia , Adenocarcinoma de Pulmão/fisiopatologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Coagulação Sanguínea/fisiologia , Fatores de Coagulação Sanguínea/análise , Fatores de Coagulação Sanguínea/metabolismo , Testes de Coagulação Sanguínea , Carcinoma Pulmonar de Células não Pequenas/fisiopatologia , Estudos de Casos e Controles , Feminino , Fibrinogênio/análise , Humanos , Neoplasias Pulmonares/fisiopatologia , Masculino , Pessoa de Meia-Idade , Tempo de Tromboplastina Parcial , Prognóstico
12.
Adv Exp Med Biol ; 1176: 81-88, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31069723

RESUMO

Hypercoagulability and altered lipid metabolism, which are observed in normal pregnancy, can be enhanced in diabetes mellitus. The aim of the study was to evaluate the influence of glycemic control on coagulation and lipid metabolism in women with pregestational (PGDM) and gestational (GDM) diabetes treated with insulin. There were 50 patients with PGDM and 101 patients with GDM enrolled into the study. Serum lipid and coagulation parameters were assessed at 18-22, 25-28, and 31-34 weeks of pregnancy and were compared within the diabetic groups with reference to the effectiveness of glycemia control. We found that poor glycemic control was associated with shortened activated partial thromboplastin time (APTT) and increased activity of antithrombin III (ATIII) in both diabetic groups and with a higher plasminogen activator inhibitor (PAI-1) content level in the GDM group. Poorly controlled PGDM was associated with higher levels of total cholesterol and high-density cholesterol (HDL) in the second trimester and triglycerides in the third trimester. In patients with poorly controlled GDM, a higher concentration of HDL was observed in third trimester, whereas a higher triglyceride level was found in both second and third trimesters. Positive correlations between total cholesterol and APTT and between triglyceride and APTT and ATIII were found in the poorly controlled PGDM group. We conclude that poor glycemic control of diabetic pregnancy impacts both lipid metabolism and the blood coagulation system.


Assuntos
Coagulação Sanguínea , Diabetes Gestacional , Metabolismo dos Lipídeos , Coagulação Sanguínea/fisiologia , Colesterol/sangue , Diabetes Gestacional/fisiopatologia , Feminino , Humanos , Metabolismo dos Lipídeos/fisiologia , Gravidez , Triglicerídeos/sangue
13.
Anaesthesia ; 74(7): 883-890, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31032890

RESUMO

Coagulopathy in patients with traumatic brain injury is associated with an increase in morbidity and mortality. Although timely and aggressive treatment of coagulopathy is of paramount importance, excessive transfusion of blood products has been linked with poor long-term outcomes in patients with traumatic brain injury. A point-of-care thromboelastometric-guided algorithm could assist in creating a more individually tailored approach to each patient. The aim of this study was to evaluate the feasibility of implementing a thromboelastometric-guided algorithm in centres that were formerly naïve to thromboelastometry. Hence, we developed such an algorithm and provided training to four centres across Europe to direct the haemostatic management of patients with severe traumatic brain injury. The primary outcome was adherence to the algorithm and timing of the availability of relevant results. Thirty-two patients were included in the study. Complete adherence to the algorithm was observed in 20 out of 32 cases. The availability of thromboelastometric results after hospital admission was reported significantly earlier than conventional coagulation tests (median (IQR [range]) 33 (20-40 [14-250]) min vs. 71 (51-101 [32-290]) min; p = 0.037). Although only 5 out of 32 patients had abnormalities of conventional coagulation tests, 21 out of 32 patients had a coagulopathic baseline thromboelastometric trace. Implementing a thromboelastometric-guided algorithm for the haemostatic therapy of traumatic brain injury is feasible in centres formerly naïve to this technology and may lead to more rapid and precise coagulation management. Further large-scale studies are warranted to confirm the results of this pilot trial and evaluate clinical outcomes.


Assuntos
Transtornos da Coagulação Sanguínea/complicações , Transtornos da Coagulação Sanguínea/terapia , Lesões Encefálicas Traumáticas/complicações , Hemostasia/fisiologia , Tromboelastografia/métodos , Coagulação Sanguínea/fisiologia , Europa (Continente) , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Sistemas Automatizados de Assistência Junto ao Leito , Guias de Prática Clínica como Assunto , Estudos Prospectivos
14.
Surgery ; 165(6): 1108-1115, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31027837

RESUMO

BACKGROUND: Acute traumatic coagulopathy has been described in adult trauma patients. Acute traumatic coagulopathy may be associated with higher mortality and morbidity in pediatric trauma patients. We aimed to (1) compare acute traumatic coagulopathy incidence among various age groups, using age-adjusted normal reference values for three tests of coagulation, and (2) compare acute traumatic coagulopathy-associated mortality by age. METHODS: We queried our institutional trauma database for all level 1 and 2 activations with an injury severity score ≥ 9 during 2012 to 2017. Demographics, injury information, and coagulation test results were collected. Coagulopathy was defined using published age-specific and assay-specific parameters. Variables were compared among age groups (children, adults, and older adults), and logistic regression was used to determine independent associations with mortality. RESULTS: A total of 1,983 patients were included with a median injury severity score of 17 and mortality of 12%. Prolonged partial thromboplastin time, prolonged international normalized ratio, and hypofibrinogenemia were all strongly associated with mortality among adults and children, but not among older adults (P < .001, P < .001, and P > .01, respectively). Logistic regression revealed an independent association between prolonged partial thromboplastin time and mortality (P < .001). CONCLUSION: Prolonged partial thromboplastin time/international normalized ratio and hypofibrinogenemia were common among trauma patients of all ages and were associated with mortality among children and adults, but not older adults, perhaps implicating age-related hemostatic biologic differences.


Assuntos
Transtornos da Coagulação Sanguínea/mortalidade , Ferimentos e Lesões/mortalidade , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/sangue , Envelhecimento/fisiologia , Coagulação Sanguínea/fisiologia , Transtornos da Coagulação Sanguínea/diagnóstico , Transtornos da Coagulação Sanguínea/etiologia , Criança , Pré-Escolar , Feminino , Fibrinogênio/análise , Mortalidade Hospitalar , Humanos , Incidência , Escala de Gravidade do Ferimento , Coeficiente Internacional Normatizado , Masculino , Pessoa de Meia-Idade , Tempo de Tromboplastina Parcial , Fatores de Risco , Ferimentos e Lesões/complicações , Ferimentos e Lesões/diagnóstico , Adulto Jovem
15.
Transfus Apher Sci ; 58(2): 216-222, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30954379

RESUMO

The contact system initiates the intrinsic pathway of coagulation and is started by Factor XII activation, which then activates prekallicrein to kallicrein and Factor XI to Factor XIa and, in the presence of high molecular weight kininogen, forms a "contact phase activation loop", that amplifies Factor XII activation. FXII deficiency is not associated with bleeding tendencies, but when the blood clots, the thrombus is less dense, thus favoring antithrombotic protection. Activated Factor XII inhibition emerges as an efficient target for preventing thrombo-embolic diseases without inducing a hemorrhagic risk. Activated Factor XII exhibits other activities, in that it can activate complement and provoke inflammation, contributing to innate immunity. It also stimulates fibrinolysis through uPA activation from scu-PA. Among the other components of the contact phase, Factor XI has a more important role in coagulation pathways and can directly activate FX, FVIII and FV, in a FIX independent pathway. Its deficiency is associated with a mild bleeding diathesis ("pseudo-hemophilia" or hemophilia C), with a variable incidence among kindreds. Recently, the occurrence of thrombotic events the same day following infusion of immunoglobulin concentrates has been demonstrated to be caused by the presence of trace amounts of activated Factor XI, pointing out the key role of this factor for thrombogenicity. Prekallicrein can be activated at the endothelial surface in the presence of high molecular weight kininogen, whose cleavage generates bradykinins and contributes to vessel tonicity and inflammation. The contact phase, through its activation loop, is then an important physiological system, which can initiate and regulate various biological functions and is at the crossroads of various biological activities. Many of the body's physiological functions are intimately linked between them, making the global approach of special usefulness for understanding the interactions which can result from any abnormality of one of them. New pharmaceutical drugs targeting a defined activity need to be investigated for all the possible interferences or side effects. In this article we aim to present and summarize the present understanding of contact phase system activation and regulation, its involvement in various physiological functions, and the laboratory tools for its exploration.


Assuntos
Transtornos da Coagulação Sanguínea/fisiopatologia , Coagulação Sanguínea/fisiologia , Fibrinólise/fisiologia , Humanos
16.
Khirurgiia (Mosk) ; (2): 65-71, 2019.
Artigo em Russo | MEDLINE | ID: mdl-30855593

RESUMO

AIM: To evaluate the effectiveness of the Remaxol in the correction of hemostatic system in patients with severe acute peritonitis. MATERIAL AND METHODS: 52 patients with acute peritonitis of different severity were examined, and divided into 4 groups: I - mild, II - moderate, III - severe. The patients of these groups had treated using standard therapy. The IV group had patients with severe peritonitis, who received an additional Remaxol. The hemostasis system was evaluated using a TEG 5000 thromboelastograph and biochemical tests. RESULTS: It has been established that the acute peritonitis is accompanied by significant hemostatic disorders - hypercogulation and hyperfibrinolysis, independently of the disease severity. CONCLUSION: In the severe peritonitis, disorders of the coagulation-lytic system were especially expressed. The use of the Remaxol in patients of this group led to a decrease the blood coagulation disorders.


Assuntos
Transtornos da Coagulação Sanguínea/tratamento farmacológico , Coagulação Sanguínea/efeitos dos fármacos , Hemostasia/efeitos dos fármacos , Hemostáticos/uso terapêutico , Peritonite/fisiopatologia , Succinatos/uso terapêutico , Coagulação Sanguínea/fisiologia , Transtornos da Coagulação Sanguínea/diagnóstico , Transtornos da Coagulação Sanguínea/etiologia , Transtornos da Coagulação Sanguínea/fisiopatologia , Hemostasia/fisiologia , Hemostáticos/farmacologia , Humanos , Peritonite/complicações , Succinatos/farmacologia , Tromboelastografia
17.
Crit Care ; 23(1): 98, 2019 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-30917843

RESUMO

BACKGROUND: Severe traumatic injury continues to present challenges to healthcare systems around the world, and post-traumatic bleeding remains a leading cause of potentially preventable death among injured patients. Now in its fifth edition, this document aims to provide guidance on the management of major bleeding and coagulopathy following traumatic injury and encourages adaptation of the guiding principles described here to individual institutional circumstances and resources. METHODS: The pan-European, multidisciplinary Task Force for Advanced Bleeding Care in Trauma was founded in 2004, and the current author group included representatives of six relevant European professional societies. The group applied a structured, evidence-based consensus approach to address scientific queries that served as the basis for each recommendation and supporting rationale. Expert opinion and current clinical practice were also considered, particularly in areas in which randomised clinical trials have not or cannot be performed. Existing recommendations were re-examined and revised based on scientific evidence that has emerged since the previous edition and observed shifts in clinical practice. New recommendations were formulated to reflect current clinical concerns and areas in which new research data have been generated. RESULTS: Advances in our understanding of the pathophysiology of post-traumatic coagulopathy have supported improved management strategies, including evidence that early, individualised goal-directed treatment improves the outcome of severely injured patients. The overall organisation of the current guideline has been designed to reflect the clinical decision-making process along the patient pathway in an approximate temporal sequence. Recommendations are grouped behind the rationale for key decision points, which are patient- or problem-oriented rather than related to specific treatment modalities. While these recommendations provide guidance for the diagnosis and treatment of major bleeding and coagulopathy, emerging evidence supports the author group's belief that the greatest outcome improvement can be achieved through education and the establishment of and adherence to local clinical management algorithms. CONCLUSIONS: A multidisciplinary approach and adherence to evidence-based guidance are key to improving patient outcomes. If incorporated into local practice, these clinical practice guidelines have the potential to ensure a uniform standard of care across Europe and beyond and better outcomes for the severely bleeding trauma patient.


Assuntos
Coagulação Sanguínea/efeitos dos fármacos , Guias como Assunto , Hemorragia/tratamento farmacológico , Ferimentos e Lesões/complicações , Coagulação Sanguínea/fisiologia , Encefalocele/prevenção & controle , Europa (Continente) , Medicina Baseada em Evidências/métodos , Medicina Baseada em Evidências/tendências , Humanos , Respiração Artificial/métodos , Ferimentos e Lesões/tratamento farmacológico
18.
Biomech Model Mechanobiol ; 18(4): 1139-1153, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30900051

RESUMO

Thrombus formation is one of the main issues in the development of blood-contacting medical devices. This article focuses on the modeling of one aspect of thrombosis, the coagulation cascade, which is initiated by the contact activation at the device surface and forms thrombin. Models exist representing the coagulation cascade by a series of reactions, usually solved in quiescent plasma. However, large parameter uncertainty involved in the kinetic models can affect the predictive capabilities of this approach. In addition, the large number of reactions of the kinetic models prevents their use in the simulation of complex flow configurations encountered in medical devices. In the current work, both issues are addressed to improve the applicability and fidelity of kinetic models. A sensitivity analysis is performed by two different techniques to identify the most sensitive parameters of an existing detailed kinetic model of the coagulation cascade. The results are used to select the form of a novel reduced model of the coagulation cascade which relies on eight chemical reactors only. Then, once its parameters have been calibrated thanks to the Bayesian inference, this model shows good predictive capabilities for different initial conditions.


Assuntos
Coagulação Sanguínea/fisiologia , Modelos Biológicos , Teorema de Bayes , Simulação por Computador , Humanos , Cinética , Trombina/metabolismo
19.
Am J Cardiol ; 123(10): 1696-1702, 2019 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-30885417

RESUMO

Adults with cyanotic congenital heart diseases (CCHD) have a higher risk for bleeding, but also for thrombosis. Rotational thromboelastometry (RT), using tissue factor (EXTEM), a contact activator (INTEM) or cytochalasin (FIBTEM), assesses coagulation by determining the time to initiation of clotting (CT) and clot firmness (MCF) including platelet-fibrin-interaction. The aim of this study was to evaluate RT and whole blood impedance aggregometry (IA) in CCHD compared with a control group without chronic cyanosis (NCCHD). These were used to establish normal reference ranges. We prospectively included 124 patients (76 CCHD, 48 NCCHD). Mean oxygen saturation in CCHD was 81.5%, and 98% in NCCHD (p <0.001). Fifty-five CCHD and 1 NCCHD had pulmonary hypertension. Eisenmenger syndrome was present in 39 CCHD (51.3%). Hemoglobin, hematocrit, and reticulocyte levels were significantly higher in CCHD, and they also showed more thrombocytopenia. Platelet aggregation was under normal range in 89.5% of CCHD after triggering with ADP, in 85.5% after triggering with arachidonic acid (ASPI) and in 73.7% after TRAP-6. RT showed significantly longer clotting times and reduced clot firmness in both EXTEM and INTEM tests. FIBTEM-MCF was also significantly reduced. Moderate inverse correlation was found between platelet count and erythrocytes (r = -0.608, p <0.001). Significant correlations were found between platelet number and RT-parameters as well as with all IA parameters. In conclusion, according to RT and IA, CCHD present hypocoagulable disorders. No signs of hypercoagulability were found.


Assuntos
Transtornos da Coagulação Sanguínea/diagnóstico , Coagulação Sanguínea/fisiologia , Cianose/complicações , Cardiopatias Congênitas/complicações , Agregação Plaquetária/fisiologia , Tromboelastografia/métodos , Adulto , Transtornos da Coagulação Sanguínea/sangue , Transtornos da Coagulação Sanguínea/complicações , Cianose/sangue , Cianose/congênito , Feminino , Cardiopatias Congênitas/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Reprodutibilidade dos Testes , Adulto Jovem
20.
Immunity ; 50(4): 1033-1042.e6, 2019 04 16.
Artigo em Inglês | MEDLINE | ID: mdl-30926232

RESUMO

Ancient organisms have a combined coagulation and immune system, and although links between inflammation and hemostasis exist in mammals, they are indirect and slower to act. Here we investigated direct links between mammalian immune and coagulation systems by examining cytokine proproteins for potential thrombin protease consensus sites. We found that interleukin (IL)-1α is directly activated by thrombin. Thrombin cleaved pro-IL-1α at a site perfectly conserved across disparate species, indicating functional importance. Surface pro-IL-1α on macrophages and activated platelets was cleaved and activated by thrombin, while tissue factor, a potent thrombin activator, colocalized with pro-IL-1α in the epidermis. Mice bearing a mutation in the IL-1α thrombin cleavage site (R114Q) exhibited defects in efficient wound healing and rapid thrombopoiesis after acute platelet loss. Thrombin-cleaved IL-1α was detected in humans during sepsis, pointing to the relevance of this pathway for normal physiology and the pathogenesis of inflammatory and thrombotic diseases.


Assuntos
Coagulação Sanguínea/fisiologia , Sistema Imunitário/imunologia , Interleucina-1alfa/fisiologia , Trombina/fisiologia , Imunidade Adaptativa , Sequência de Aminoácidos , Animais , Plaquetas/metabolismo , Humanos , Imunidade Inata , Interleucina-1alfa/genética , Interleucina-1alfa/imunologia , Queratinócitos/metabolismo , Macrófagos/metabolismo , Mamíferos/imunologia , Camundongos , Precursores de Proteínas/metabolismo , Seleção Genética , Sepse/imunologia , Alinhamento de Sequência , Homologia de Sequência de Aminoácidos , Trombopoese/imunologia , Cicatrização/imunologia
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