RESUMO
The term 'routine coagulation' typically applies to hemostasis tests routinely performed in hematology laboratories, often available 24/7, and potentially ordered urgently. These tests would comprise of the prothrombin time (PT), the PT converted to an international normalized ratio, the activated partial thromboplastin time (often called partial thromboplastin time in North American laboratories) and potentially the thrombin time, the D-dimer assay, and fibrinogen assays. Although other tests could feasibly be offered (testing feasible), there are good reasons for not including all of these other tests in all routine coagulation laboratories.
Assuntos
Tempo de Protrombina , Humanos , Testes de Coagulação Sanguínea , Coagulação Sanguínea , Tempo de Tromboplastina Parcial , Transtornos da Coagulação Sanguínea/diagnóstico , Transtornos da Coagulação Sanguínea/sangue , Produtos de Degradação da Fibrina e do Fibrinogênio/análiseRESUMO
Patients with liver cirrhosis often exhibit complex alterations in their hemostatic system that can be associated with both bleeding and thrombotic complications. While prophylactic correction of abnormal coagulation parameters should be avoided, an individualized approach is recommended prior to invasive procedures, whereby specific preventive measures to stabilize hemostasis should be based on the periprocedural bleeding risk. While the haemostatic system of patients with compensated cirrhosis is often in a rebalanced haemostatic state due to a parallel decline in both pro- and anti-haemostatic factors, a decompensation of liver cirrhosis can lead to destabilization of this fragile equilibrium. Since conventional coagulation tests do not adequately capture the complex changes in the hemostatic system in cirrhosis, functional analysis methods such as viscoelastic tests or thrombin generation assays can be used for evaluating the coagulation status. This review describes the underlying pathophysiological changes in the hemostatic system in liver cirrhosis, provides an overview of diagnostic methods and discusses therapeutic measures in case of bleeding and thrombotic complications.
Assuntos
Transtornos da Coagulação Sanguínea , Cirrose Hepática , Humanos , Cirrose Hepática/complicações , Cirrose Hepática/diagnóstico , Transtornos da Coagulação Sanguínea/diagnóstico , Transtornos da Coagulação Sanguínea/terapia , Transtornos da Coagulação Sanguínea/etiologia , Testes de Coagulação Sanguínea , Hemorragia/etiologia , Hemorragia/terapia , Hemorragia/diagnóstico , Trombose/diagnóstico , Trombose/etiologia , Trombose/terapia , Trombose/prevenção & controleRESUMO
INTRODUCTION: Blood transfusion is one of the most common medical practices worldwide. However, current scientific literature has shown that the immunomodulatory effects of blood transfusion are associated with an increased likelihood of infection, prolonged hospitalization, and morbimortality. Also, it means high costs for healthcare systems. METHODS: In this context, acknowledging that blood transfusions are essentially heterologous cell transplantations, the use of therapeutic options has gained strength and is collectively known as the patient blood management (PBM) program. PBM is an approach based on three main pillars: (1) treating anemias and coagulopathies in an optimized manner, especially in the preoperative period; (2) optimizing perioperative hemostasis and the use of blood recovery systems to avoid the loss of the patient's blood; (3) anemia tolerance, with improved oxygen delivery and reduced oxygen demand, particularly in the postoperative period. RESULTS: Current scientific evidence supports the effectiveness of PBM by reducing the need for blood transfusions, decreasing associated complications, and promoting more efficient and safer blood management. Thus, PBM not only improves clinical outcomes for patients but also contributes to the economic sustainability of healthcare systems. CONCLUSION: The aim of this review was to summarize PBM strategies in a comprehensive, evidence-based approach through a systematic and structured model for PBM implementation in tertiary hospitals. The recommendations proposed herein are from researchers and experts of a high-complexity university hospital in the network of the Sistema Único de Saúde, presenting itself as a strategy that can be followed as a guideline for PBM implementation in other settings.
Assuntos
Anemia , Transfusão de Sangue , Humanos , Transfusão de Sangue/normas , Anemia/terapia , Anemia/prevenção & controle , Transtornos da Coagulação Sanguínea/terapia , Transtornos da Coagulação Sanguínea/prevenção & controleRESUMO
BACKGROUND: Trauma induced coagulopathy remains to be an important cause of high transfusion requirements and mortality and shock induced endotheliopathy (SHINE) has been implicated. METHODS: European multicenter observational study of adult trauma patients with injury severity score ≥ 16 arriving within 2 h from injury to the trauma centers. Admission blood samples obtained were used for analysis of the SHINE biomarkers (syndecan-1, soluble thrombomodulin, adrenaline) and extensive analysis of coagulation, -and fibrinolytic factors together with collection of clinical data. Hierarchical clustering of the SHINE biomarkers was used to identify the SHINE phenotypes. RESULTS: The 313 patients clustered into four SHINE phenotypes. Phenotype 2, having the highest glycocalyx shedding, encompassing 22% of the whole cohort, had severe coagulopathy with lower levels of prothrombin, FV, IX, X, XI and severe hyperfibrinolysis with higher plasmin - alpha 2-antiplasmin (PAP) - and tPA levels and lower alpha2 - antiplasmin levels. This phenotype had significantly higher transfusion requirements and higher mortality (39% vs. 23%, 15% and 14%) but similar injury severity score (ISS) compared to the others phenotypes. CONCLUSIONS: Hierarchical clustering identified four SHINE phenotype in a cohort of trauma patients. Trauma induced coagulopathy was confined to only one of the SHINE phenotypes, encompassing 22% of the total cohort. This phenotype was characterized by severe hypocoagulability and hyperfibrinolysis, which translated to significantly higher transfusion requirements and higher mortality compared to the other SHINE phenotypes with similar injury severity, warranting further investigation.
Assuntos
Transtornos da Coagulação Sanguínea , Escala de Gravidade do Ferimento , Fenótipo , Ferimentos e Lesões , Humanos , Masculino , Feminino , Transtornos da Coagulação Sanguínea/etiologia , Transtornos da Coagulação Sanguínea/sangue , Adulto , Pessoa de Meia-Idade , Ferimentos e Lesões/complicações , Ferimentos e Lesões/sangue , Biomarcadores/sangue , Endotélio Vascular/fisiopatologia , Endotélio Vascular/lesões , Europa (Continente)/epidemiologiaRESUMO
Coagulation disorders are common in Kawasaki disease (KD). The main objectives of the present study were to probe the associations of coagulation profiles with clinical classification, IVIG responsiveness, coronary artery abnormalities (CAAs) in the acute episode of KD. A total of 313 KD children were recruited and divided into six subgroups, including complete KD (n = 217), incomplete KD (n = 96), IVIG-responsive KD (n = 293), IVIG-nonresponsive KD (n = 20), coronary artery noninvolvement KD (n = 284) and coronary artery involvement KD (n = 29). Blood samples were collected within 24-h pre-IVIG therapy and 48-h post-IVIG therapy. Coagulation profiles, conventional inflammatory mediators and blood cell counts were detected. Echocardiography was performed during the period from 2- to 14-day post-IVIG infusion. In addition, 315 sex- and age-matched healthy children were enrolled as the controls. (1) Before IVIG therapy, coagulation disorders were more prone to appear in KD patients than in healthy controls, and could be overcome by IVIG therapy. FIB and DD significantly increased in the acute phase of KD, whereas reduced to normal levels after IVIG therapy. (2) PT and APTT were significantly longer in patients with complete KD when compared with their incomplete counterparts after IVIG therapy. (3) The larger δDD, δFDP and the smaller δPT, δINR predicted IVIG nonresponsiveness. (4) The higher δDD and δFDP correlated with a higher risk for CAAs (DD: r = -0.72, FDP: r = -0.54). Coagulation disorders are correlated with complete phenotype, IVIG nonresponsiveness and CAA occurrence in the acute episode of KD, and can be rectified by synergistic effects of IVIG and aspirin.
Assuntos
Imunoglobulinas Intravenosas , Síndrome de Linfonodos Mucocutâneos , Humanos , Síndrome de Linfonodos Mucocutâneos/tratamento farmacológico , Síndrome de Linfonodos Mucocutâneos/sangue , Síndrome de Linfonodos Mucocutâneos/complicações , Imunoglobulinas Intravenosas/uso terapêutico , Masculino , Feminino , Pré-Escolar , Lactente , Criança , Vasos Coronários/patologia , Vasos Coronários/diagnóstico por imagem , Ecocardiografia , Coagulação Sanguínea/efeitos dos fármacos , Resultado do Tratamento , Transtornos da Coagulação Sanguínea/tratamento farmacológico , Transtornos da Coagulação Sanguínea/etiologia , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/tratamento farmacológicoRESUMO
Disorders of blood coagulation can lead to manifest spontaneous bleeding and an increased risk of bleeding during surgical procedures and interventions. Pathophysiologically, a distinction can be made between defects in primary haemostasis, which lead to impaired platelet adhesion and platelet aggregation, and disorders of secondary (plasmatic) haemostasis, which are characterised by impaired fibrin formation or fibrin stabilisation. Aetiologically, a distinction can be made between rare genetically-determined hereditary defects and common acquired coagulation disorders, which may be based on different pathomechanisms. This overview is intended to provide ophthalmic surgeons with a basis for the perioperative management of patients with genetically determined coagulation disorders undergoing ophthalmic surgery. As there are no specific recommendations in this regard, the recommendations are based on the procedure for other surgical interventions, taking into account the specific bleeding risk associated with ophthalmic surgery.
Assuntos
Transtornos da Coagulação Sanguínea , Procedimentos Cirúrgicos Oftalmológicos , Assistência Perioperatória , Humanos , Procedimentos Cirúrgicos Oftalmológicos/métodos , Procedimentos Cirúrgicos Oftalmológicos/efeitos adversos , Transtornos da Coagulação Sanguínea/diagnóstico , Transtornos da Coagulação Sanguínea/etiologia , Assistência Perioperatória/métodos , Perda Sanguínea Cirúrgica/prevenção & controleRESUMO
Trauma is the leading cause of death in individuals up to 45 years of age. Alterations in platelet function are a critical component of trauma-induced coagulopathy (TIC), yet these changes and the potential resulting dysfunction is incompletely understood. The lack of clinical assays available to explore platelet function in this patient population has hindered detailed understanding of the role of platelets in TIC. The objective of this study was to assess trauma patient ex vivo flow-dependent platelet hemostatic capacity in a microfluidic model. We hypothesized that trauma patients would have flow-regime dependent alterations in platelet function. Blood was collected from trauma patients with level I activations (N = 34) within 60 min of hospital arrival, as well as healthy volunteer controls (N = 10). Samples were perfused through a microfluidic model of injury at venous and arterial shear rates, and a subset of experiments were performed after incubation with fluorescent anti-CD41 to quantify platelets. Complete blood counts were performed as well as plasma-based assays to quantify coagulation times, fibrinogen, and von Willebrand factor (VWF). Exploratory correlation analyses were employed to identify relationships with microfluidic hemostatic parameters. Trauma patients had increased microfluidic bleeding times compared to healthy controls. While trauma patient samples were able to deposit a substantial amount of clot in the model injury site, the platelet contribution to microfluidic hemostasis was attenuated. Trauma patients had largely normal hematology and plasma-based coagulation times, yet had elevated D-Dimer and VWF. Venous microfluidic bleeding time negatively correlated with VWF, D-Dimer, and mean platelet volume (MPV), while arterial microfluidic bleeding time positively correlated with oxygenation. Arterial clot growth rate negatively correlated with red cell count, and positively with mean corpuscular volume (MCV). We observed changes in clot composition in trauma patient samples reflected by significantly diminished platelet contribution, which resulted in reduced hemostatic function in a microfluidic model of vessel injury. We observed a reduction in platelet clot contribution under both venous and arterial flow ex vivo in trauma patient samples. While our population was heterogenous and had relatively mild injury severity, microfluidic hemostatic parameters correlated with different patient-specific data depending on the flow setting, indicating potentially differential mechanistic pathways contributing to platelet hemostatic capacity in the context of TIC. These data were generated with the goal of identifying key features of platelet dysfunction in bleeding trauma patients under conditions of flow and to determine if these features correlate with clinically available metrics, thus providing preliminary surrogate markers of physiological platelet dysfunction to be further studied across larger cohorts. Future studies will continue to explore those relationships and further define mechanisms of TIC and their relationship with patient outcomes.
Assuntos
Plaquetas , Hemostasia , Microfluídica , Ferimentos e Lesões , Humanos , Plaquetas/metabolismo , Masculino , Feminino , Adulto , Ferimentos e Lesões/sangue , Ferimentos e Lesões/complicações , Microfluídica/métodos , Pessoa de Meia-Idade , Transtornos da Coagulação Sanguínea/etiologia , Transtornos da Coagulação Sanguínea/sangue , Fator de von Willebrand/metabolismo , Fibrinogênio/metabolismo , Estudos de Casos e Controles , Tempo de SangramentoRESUMO
BACKGROUND: The objective of this study was to explore the correlation between statin administration in the intensive care unit (ICU) setting and the in-hospital mortality risk of patients suffering from sepsis-induced coagulopathy (SIC). METHODS: Utilizing a retrospective cohort study design, this investigation collected data from the Medical Information Mart for Intensive Care (MIMIC)-IV spanning 2008 to 2019. The diagnosis of SIC was established based on a SIC score of 4 or above. Statin usage during the ICU period was extracted from the prescription records based on the keywords of statin medications. The primary endpoint analyzed was the in-hospital mortality within the ICU, characterized by any death occurring during the ICU admission. RESULTS: During the follow-up, which had a median duration of approximately 7.28 days, 18.19% of the 4,777 SIC patients died in the ICU. Statin was linked with a decrease in the risk of in-hospital mortality for SIC patients in the ICU [hazard ratio (HR): 0.73, 95% confidence interval (CI): 0.60-0.89, P = 0.002]. Relative to rosuvastatin, the use of atorvastatin (HR: 0.54, 95% CI: 0.34-0.85, P = 0.008) or simvastatin (HR: 0.55, 95% CI: 0.33-0.92, P = 0.024), as well as combinations of multiple statins (HR: 0.36, 95% CI: 0.15-0.86, P = 0.022), was associated with a reduction in ICU in-hospital mortality risk. Subgroup analysis also suggested that the use of atorvastatin, simvastatin, or a combination of statins had an advantage over rosuvastatin in reducing ICU in-hospital mortality in SIC patients older than 65 years of age or SIC patients with respiratory failure or cardiogenic shock (all P < 0.05). CONCLUSION: The present study supports the potential benefits of statin use in mortality in SIC patients during ICU stays. The study encourages clinicians to consider the benefits of statins and supports the ongoing exploration of statins for enhanced outcomes in critical care settings.
Assuntos
Mortalidade Hospitalar , Inibidores de Hidroximetilglutaril-CoA Redutases , Unidades de Terapia Intensiva , Sepse , Humanos , Masculino , Sepse/mortalidade , Sepse/tratamento farmacológico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Feminino , Unidades de Terapia Intensiva/estatística & dados numéricos , Estudos Retrospectivos , Idoso , Pessoa de Meia-Idade , Transtornos da Coagulação Sanguínea/tratamento farmacológico , Transtornos da Coagulação Sanguínea/mortalidade , Transtornos da Coagulação Sanguínea/etiologia , Bases de Dados Factuais , Idoso de 80 Anos ou maisRESUMO
BACKGROUND AND AIM: The use of cefoperazone/sulbactam (CPZ/SAM) could commonly cause vitamin K-dependent coagulation disorders and even hemorrhage sometimes. However, there is a lack of prediction tools estimating the risk for this. This study aimed at developing and internally validating a model for predicting CPZ/SAM-associated coagulation disorders in Chinese inpatients. METHODS: A case-control study was conducted in 11,092 adult inpatients admitted to a Chinese general hospital between 2020 and 2021 and treated with CPZ/SAM. Patients with CPZ/SAM-associated coagulation disorders were identified through the Adverse Drug Events Active Surveillance and Assessment System-II and subsequent manual evaluation. Controls were selected from eligible patients who didn't develop coagulation disorders after CPZ/SAM therapy, with a 1:1 propensity score matching. The final predictors were obtained by univariable and multivariable logistic regression analyses. Internal validation and calibration for the model were performed using 1000 bootstrap resamplings. RESULTS: 258 patients were identified as CPZ/SAM-associated coagulation disorders in 2184 patients eligible for inclusions and exclusions and the incidence was 11.8%. A final population of 252 cases and 252 controls was included for model development and validation. Malnutrition (OR = 2.41 (1.56-3.77)), history of recent bleeding (OR = 1.95 (1.32-2.90)), treatment duration (OR = 1.10 (1.07-1.14)), combination with carbapenems (OR = 4.43 (1.85-11.88)), and serum creatinine (OR = 1.01 (1.00-1.01)) were identified as final predictors. The model showed good discrimination, calibration, and clinical practicality, with the validated area under the receiver operating characteristic curve being 0.723 (0.683-0.770). CONCLUSIONS: The model with good performance quantifies the risk for CPZ/SAM-associated coagulation disorders, and may support individual assessment and interventions to mitigate the risk after external validation.
Assuntos
Antibacterianos , Transtornos da Coagulação Sanguínea , Cefoperazona , Sulbactam , Humanos , Cefoperazona/uso terapêutico , Cefoperazona/efeitos adversos , Sulbactam/uso terapêutico , Sulbactam/efeitos adversos , Feminino , Masculino , Pessoa de Meia-Idade , Estudos de Casos e Controles , Idoso , Antibacterianos/efeitos adversos , Antibacterianos/uso terapêutico , China , Transtornos da Coagulação Sanguínea/induzido quimicamente , Adulto , Pacientes Internados , População do Leste AsiáticoRESUMO
Hematologic emergencies are bleeding or clotting disorders that are hereditary or acquired and must be treated emergently to avoid significant morbidity or mortality. Patients experiencing a hematologic emergency may present with spontaneous bleeding, jaundice, petechiae, or purpura. Initial diagnostic testing should include a complete blood count. Patients who have bleeding associated with a hereditary disorder should receive clotting factor replacement before diagnostic testing. Acute chest syndrome is an uncommon but serious complication of sickle cell disease. Hemolysis caused by autoimmune disorders or iatrogenic errors from blood product transfusions has a distinct clinical presentation and requires immediate action. Severe thrombocytopenia presenting as immune or thrombotic thrombocytopenic purpura should be differentiated and treated appropriately. Disseminated intravascular coagulation and trauma coagulopathy are sometimes confused with each other, but both can cause serious injury and require unique treatments. Primary care physicians should promptly recognize patients who require emergent referral to a hematologic specialist.
Assuntos
Emergências , Humanos , Doenças Hematológicas/terapia , Doenças Hematológicas/diagnóstico , Doenças Hematológicas/complicações , Transtornos da Coagulação Sanguínea/diagnóstico , Transtornos da Coagulação Sanguínea/terapia , Transtornos da Coagulação Sanguínea/etiologia , Diagnóstico DiferencialRESUMO
INTRODUCTION: The 2021 Surviving Sepsis Campaign guidelines recommend low-molecular-weight heparin for the prevention of venous thromboembolism in sepsis. However, observational studies suggest that anticoagulants as a whole may benefit severely ill sepsis patients with coagulopathy, but the optimal targets of unfractionated heparin remain unclear. This study investigated which sepsis patients could most benefit from unfractionated heparin. MATERIALS AND METHODS: In this retrospective observational study, we identified adult sepsis patients requiring urgent hospitalization from 2006 to 2019 using a large-scale Japanese medical database. Patients were divided into two groups: those receiving unfractionated heparin within 72 h of admission and those who did not. We compared in-hospital mortality, major bleeding complications, and thromboembolic events between these groups using a multivariate logistic regression model adjusted for patient and treatment variables. Additionally, we assessed the association between heparin administration and in-hospital mortality across various subgroups. RESULTS: Among 30,342 sepsis patients, 2520 received early heparin administration, and 27,822 did not. Multivariate logistic regression revealed a significant association between heparin and reduced in-hospital mortality (adjusted OR: 0.735, 95 % CI: 0.596-0.903) but no significant association with major bleeding and thromboembolic risk (adjusted OR: 1.137, 1.243; 95 % CI: 0.926-1.391, 0.853-1.788, respectively). Subgroup analyses suggested significant survival benefits associated with heparin only in the sepsis patients with moderate coagulopathy and sepsis-induced coagulopathy scores of 3 or 4 (adjusted OR: 0.452, 0.625; 95 % CI: 0.265-0.751, 0.410-0.940, respectively). CONCLUSIONS: Early heparin administration upon admission is associated with lower in-hospital mortality, especially in moderate sepsis-induced coagulopathy, and no significant increase in complications.
Assuntos
Transtornos da Coagulação Sanguínea , Heparina , Sepse , Humanos , Sepse/complicações , Sepse/tratamento farmacológico , Sepse/mortalidade , Masculino , Feminino , Heparina/uso terapêutico , Estudos Retrospectivos , Idoso , Pessoa de Meia-Idade , Transtornos da Coagulação Sanguínea/tratamento farmacológico , Transtornos da Coagulação Sanguínea/complicações , Transtornos da Coagulação Sanguínea/etiologia , Anticoagulantes/uso terapêutico , Mortalidade Hospitalar , Idoso de 80 Anos ou maisRESUMO
Phosphoglucomutase-1-congenital disorder of glycosylation (PGM1-CDG) is a rare genetic disorder caused by biallelic variants in the PGM1 gene, leading to the deficiency of the PGM1 enzyme. The most common clinical presentations include muscle involvement, failure to thrive, cleft palate, and cardiac involvement. Abnormal serum N-glycosylation, hypoglycemia, and liver function abnormalities including coagulation abnormalities are the most common laboratory abnormalities. While PGM1-CDG has been extensively studied, little is known about the extent of the coagulation abnormalities in individuals with PGM1-CDG. Unlike most CDG, some symptoms of PGM1-CDG are treatable with D-galactose (D-gal) supplementation, though reliable clinical endpoints are necessary to appropriately evaluate the potential improvement with D-gal in PGM1-CDG. Here, we aimed to describe the incidence of coagulation abnormalities in PGM1-CDG and their evolution, their relation to clinical events, and the ability of D-gal treatment to improve them. A retrospective analysis was conducted on 73 reported individuals. All individuals had a molecularly confirmed PGM1-CDG diagnosis. All incidences of antithrombin (AT), aPTT, PT, factor (F) XI, FX, FIX, FVII, protein C and protein S data and major clinical events related to coagulation abnormalities, were collected. Coagulation information was available for only 58.9 % of the reported individuals, out of which 67.4 % of PGM1-CDG individuals were reported to have abnormalities. The most frequently observed abnormality was AT (mean: 30.8% R:80-120 %) deficiency. Four individuals had major thrombotic events. Coagulation status on D-gal treatment, were reported in 19 individuals. Several factors showed improvement including AT (mean: 64.5 %), indicating galactose is beneficial in treating coagulation abnormalities in PGM1-CDG. Due to the scarcity of the reported data on coagulation parameters, we also evaluated data collected in sixteen PGM1-CDG individuals enrolled in the FCDGC Natural History Study. Longitudinal data showed improvements in several coagulant parameters and disease severity improved for almost all patients of whom we had multiple datapoints on D-gal. AT showed significant improvement on D-gal. We conclude that coagulation abnormalities are frequently present in PGM1-CDG and show improvement on D-gal. We recommend coagulation parameters should be routinely checked in individuals with PGM1-CDG or suspected of having PGM1-CDG. Finally, AT may be used as a primary or secondary clinical endpoint for upcoming clinical trials in PGM1-CDG individuals.
Assuntos
Transtornos da Coagulação Sanguínea , Defeitos Congênitos da Glicosilação , Fosfoglucomutase , Humanos , Defeitos Congênitos da Glicosilação/genética , Defeitos Congênitos da Glicosilação/complicações , Defeitos Congênitos da Glicosilação/patologia , Fosfoglucomutase/genética , Fosfoglucomutase/deficiência , Masculino , Feminino , Estudos Retrospectivos , Transtornos da Coagulação Sanguínea/genética , Transtornos da Coagulação Sanguínea/sangue , Lactente , Pré-Escolar , Criança , Adolescente , Galactose , Adulto , Adulto Jovem , Glicosilação , Recém-Nascido , Coagulação Sanguínea/genéticaRESUMO
Coagulopathy and traumatic brain injury (TBI) are complexly intertwined. In isolated TBI, coagulopathy may contribute to hemorrhagic lesion development, progression, or recurrence, as it may lead to a particular pattern of coagulopathy called TBI-induced coagulopathy (TBI-IC). We performed a retrospective and descriptive evaluation of 63 patients admitted to the Emergency Clinical Hospital Bucharest with the diagnosis of moderate/severe brain injury. In addition to demographic data, all included patients had a complete paraclinical evaluation that included rotational thromboelastometric (ROTEM) blood-clot analysis. The platelet component (PLTEM) and the endotheliopathy activation and stress index score (EASIX) were calculated. These parameters were presented comparatively according to survival at 30 days and helped define the two study groups: survivors and non-survivors at 30 days. The contribution of platelets to clot strength is derived from maximum clot elasticity (MCE) and maximum clot firmness (MCF). MCE is defined as (MCF × 100)/(100 - MCF), and PLTEM is defined as EXTEM MCE-FIBTEM MCE. EASIX is a novel biomarker recently studied in TBI patients, calculated according to the following formula: lactate dehydrogenase (U/L) × creatinine (mg/dL)/platelets (109 cells/L). Regarding the demographic data, there were no significant differences between the survivors and non-survivors. All ROTEM parameters related to clot amplitude (A5, A10, A20, MCF in EXTEM and FIBTEM channels) were higher in the group of patients who survived. Also, PLTEM was decreased in the group of deceased patients (89.71 ± 22.86 vs. 132.3 ± 16.56 p < 0.0001). The cut-off point determined with the ROC curve is 114.10, with a sensitivity of 94.74% and a specificity of 93.18%, for the detection of the negative prognosis (death at 30 days). The EASIX score was significantly higher in the patients who survived the traumatic event, with a median difference value of 1.15 (p < 0.0001). The ROC analysis of this biomarker highlights a cut-off point of 2.12, with a sensitivity of 88.64% and a specificity of 94.74% (AUC = 0.95, p < 0.0001), for the prediction of mortality. The comparative analysis of the two studied markers was performed using the Cox proportional hazard ratio and highlighted the greater influence that PLTEM has on survival time (b value = -0.05, p < 0.0001) compared to EASIX (b value = 0.49, p = 0.0026). The present retrospective study indicates the potential of the TBI-IC reflecting parameters PLTEM and EASIX as markers of mortality prognosis. Larger prospective studies are needed to confirm their combined prognostic value and use in decision-making and reduction in the burden of disease by adequate allocation of resources in a personalized and timely manner.
Assuntos
Plaquetas , Lesões Encefálicas Traumáticas , Humanos , Lesões Encefálicas Traumáticas/mortalidade , Lesões Encefálicas Traumáticas/sangue , Lesões Encefálicas Traumáticas/complicações , Lesões Encefálicas Traumáticas/fisiopatologia , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Plaquetas/metabolismo , Estudos Retrospectivos , Tromboelastografia , Idoso , Prognóstico , Biomarcadores/sangue , Transtornos da Coagulação Sanguínea/etiologia , Transtornos da Coagulação Sanguínea/mortalidade , Transtornos da Coagulação Sanguínea/sangueRESUMO
OBJECTIVE: To investigate the intervention effect and mechanism of regulating miR-155 on young rats with dysfunction of blood coagulation. METHODS: Twenty-six healthy and clean SD male rats were selected to establish the coagulopathy models. Twenty-four rats successfully established models and were randomly divided into three groups: model group, up-regulated miR-155 group and down-regulated miR-155 group, with 8 rats in each group. The expression of miR-155 was detected by real-time fluorescence quantitative polymerase chain reaction. The changes of coagulation factors and coagulation indicators were observed. Liver pathological tissues were observed by HE staining. The expressions of HMGB1-RAGE/TLRs-NF-κB signaling pathway related proteins were detected by Western blot. RESULTS: Compared with model group, the expressions of HMGB1, RAGE, TLR2, TLR4 and NF-κB were significantly increased in up-regulated miR-155 group (all P < 0.05), while decreased in down-regulated miR-155 group (all P < 0.05). Compared with model group, the expressions of coagulation factor â ¡, â ¦, â ¨, and â © were significantly decreased in up-regulated miR-155 group (all P < 0.05), while increased in down-regulated miR-155 group (P < 0.05). There was no significant difference in the expression of coagulation factor â ª among the three groups (P >0.05). Compared with model group, the levels of prothrombin time (PT) and activated partial thromboplastin time (APTT) were lower and fibrinogen (FIB) was higher in up-regulated miR-155 group (all P < 0.05), while in the down-regulated miR-155 group they were opposite. CONCLUSION: Down-regulation of miR-155 can effectively improve coagulation factors and coagulation indexes and inhibit inflammation in young rats with dysfunction of blood coagulopathy, and the mechanism may be related to HMGB1-RAGE/TLRs-NF-κB signaling pathway.
Assuntos
Coagulação Sanguínea , Proteína HMGB1 , MicroRNAs , NF-kappa B , Ratos Sprague-Dawley , Transdução de Sinais , Animais , Ratos , Masculino , NF-kappa B/metabolismo , Proteína HMGB1/metabolismo , Transtornos da Coagulação Sanguínea , Regulação para Baixo , Receptor 4 Toll-Like/metabolismo , Fatores de Coagulação Sanguínea/metabolismo , Receptor 2 Toll-Like/metabolismoRESUMO
COVID-associated coagulopathy seemly plays a key role in post-acute sequelae of SARS- CoV-2 infection. However, the underlying pathophysiological mechanisms are poorly understood, largely due to the lack of suitable animal models that recapitulate key clinical and pathological symptoms. Here, we fully characterized AC70 line of human ACE2 transgenic (AC70 hACE2 Tg) mice for SARS-CoV-2 infection. We noted that this model is highly permissive to SARS-CoV-2 with values of 50% lethal dose and infectious dose as ~ 3 and ~ 0.5 TCID50 of SARS-CoV-2, respectively. Mice infected with 105 TCID50 of SARS-CoV-2 rapidly succumbed to infection with 100% mortality within 5 days. Lung and brain were the prime tissues harboring high viral titers, accompanied by histopathology. However, viral RNA and inflammatory mediators could be detectable in other organs, suggesting the nature of a systemic infection. Lethal challenge of AC70 hACE2 Tg mice caused acute onset of leukopenia, lymphopenia, along with an increased neutrophil-to-lymphocyte ratio (NLR). Importantly, infected animals recapitulated key features of COVID-19-associated coagulopathy. SARS-CoV-2 could induce the release of circulating neutrophil extracellular traps (NETs), along with activated platelet/endothelium marker. Immunohistochemical staining with anti-platelet factor-4 (PF4) antibody revealed profound platelet aggregates especially within blocked veins of the lungs. We showed that acute SARS-CoV-2 infection triggered a hypercoagulable state coexisting with ill-regulated fibrinolysis. Finally, we highlighted the potential role of Annexin A2 (ANXA2) in fibrinolytic failure. ANXA2 is a calcium-dependent phospholipid-binding protein that forms a heterotertrameric complexes localized at the extracellular membranes with two S100A10 small molecules acting as a co-receptor for tissue-plasminogen activator (t-PA), tightly involved in cell surface fibrinolysis. Thus, our results revealing elevated IgG type anti-ANXA2 antibody production, downregulated de novo ANXA2/S100A10 synthesis, and reduced ANXA2/S100A10 association in infected mice, this protein might serve as druggable targets for development of antithrombotic and/or anti-fibrinolytic agents to attenuate pathogenesis of COVID-19.
Assuntos
Enzima de Conversão de Angiotensina 2 , COVID-19 , Modelos Animais de Doenças , Camundongos Transgênicos , SARS-CoV-2 , Animais , COVID-19/patologia , COVID-19/complicações , COVID-19/virologia , COVID-19/metabolismo , Camundongos , Enzima de Conversão de Angiotensina 2/metabolismo , Enzima de Conversão de Angiotensina 2/genética , Humanos , Transtornos da Coagulação Sanguínea/virologia , Transtornos da Coagulação Sanguínea/patologia , Pneumonia Viral/virologia , Pneumonia Viral/patologia , Pneumonia Viral/metabolismo , Betacoronavirus , Pulmão/virologia , Pulmão/patologia , Pulmão/metabolismo , Infecções por Coronavirus/virologia , Infecções por Coronavirus/patologia , Infecções por Coronavirus/complicações , Pandemias , Armadilhas Extracelulares/metabolismoRESUMO
INTRODUCTION: Coronavirus 2019 symptoms include coagulopathy and thromboembolic risk. Using one parameter to diagnose coagulopathy has little predictive value. OBJECTIVE: This study will examine if D-dimer and APTT testing can predict COVID-19 severity and aid triage and manage patients. METHODS: 214 COVID-19 patients were enrolled and classified into two categories based on their respiratory manifestations; mild (126 cases) and severe (88 cases). Patient data regarding age, gender, D-Dimer level, and APTT level were collected. When both D-Dimer and APTT levels were abnormal, in this study, the patient was considered to have a coagulation disorder. Indicators of coagulation in the COVID-19 patients were collected and compared between the two groups. Chi-square (χ2) tests were used to determine the significant differences between coagulation disorders in the two groups. RESULTS: Our findings showed that patients with coagulopathies were more likely to belong to the severe group. Within the two groups of patients, the rate of coagulation disorders was as follows: mild = 8.8 % within coagulation disorders, 4.8% within the two Groups; severe = 91.2 % within coagulation disorders, 77.8 % within the two Groups. There was a statistically significant relationship between coagulation disorder and severe COVID-19 patients compared to mild patients (p < 0.05). CONCLUSIONS: Coagulation disorders are more likely to occur in severe COVID-19 patients. D-Dimer and APTT tests are significant indicators for predicting COVID-19 severity. Our research found an abnormal pattern of coagulation disorders and COVID-19 severity that should be considered in the COVID-19 treatment protocol.