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1.
Clin Appl Thromb Hemost ; 30: 10760296241283166, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39279317

RESUMEN

The study aims to evaluate the prognosis and risk factors of sepsis-associated thrombocytopenia (SAT) among patients with coagulopathy, and to provide evidence of the relationship between adverse outcomes and potential risks. Patients with sepsis-associated coagulopathy were included in the study from January 2014 to December 2022. The primary outcome was sepsis-associated thrombocytopenia (platelet count less than 100 *109/L), which was evaluated by logistic regression models adjusted for demographic characteristics and comorbidities. Among patients in the SAT group, 54% developed severe SAT, while 16% of these patients recovered from thrombocytopenia. The in-hospital mortality rate was significantly higher in the SAT group compared to the non-SAT group (31% in SAT group vs 23.9% in non-SAT group, p = 0.029). Even after adjusting for age, gender, Charlson comorbidity, white blood cell, and Sequential Organ Failure Assessment score, the differences in mortality rate persisted (Odds Ratio 0.72, [95% Confidence Interval 0.52-0.92]). Correlation analyses revealed that prothrombin time (r = 0.08, p = 0.50), international normalized ratio (r = 0.08, p = 0.42), prothrombin activity (r = -0.06, p > 0.999), D-dimer (r = -0.02, p > 0.999), and inflammatory parameters such as C-reactive protein (r = -0.11, p = 0.37) were not significantly correlated with platelet counts. According to subgroup analyses, patients with lung infection complicated by SAT had slightly higher mortality (OR 0.66, [95% CI, 0.46 to 0.94]). Sepsis-associated coagulopathy indicates a subset of critical ill patients, with those experiencing thrombocytopenia at greater risk for in-hospital death compared to those without it.


Asunto(s)
Trastornos de la Coagulación Sanguínea , Sepsis , Trombocitopenia , Humanos , Sepsis/complicaciones , Sepsis/mortalidad , Sepsis/sangre , Masculino , Femenino , Factores de Riesgo , Trombocitopenia/sangre , Anciano , Persona de Mediana Edad , Trastornos de la Coagulación Sanguínea/etiología , Trastornos de la Coagulación Sanguínea/sangre , Trastornos de la Coagulación Sanguínea/mortalidad , Mortalidad Hospitalaria
2.
Sci Rep ; 14(1): 21229, 2024 09 11.
Artículo en Inglés | MEDLINE | ID: mdl-39261512

RESUMEN

SETANTA (Study of HEarT DiseAse and ImmuNiTy After COVID-19 in Ireland) study aimed to investigate symptom burden and incidence of cardiac abnormalities after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)/COVID-19 and to correlate these results with biomarkers of immunological response and coagulation. SETANTA was a prospective, single-arm observational cross-sectional study condcuted in a primary practice setting, and prospectively registered with ClinicalTrials.gov (identifier: NCT04823182). Patients with recent COVID-19 infection (≥ 6 weeks and ≤ 12 months) were prospectively enrolled. Primary outcomes of interest were markers of cardiac injury detected by cardiac magnetic resonance imaging (CMR), which included left ventricular ejection fraction, late gadolinium enhancement and pericardial abnormalities, as well as relevant biomarkers testing immunological response and coagulopathy. 100 patients (n = 129 approached) were included, amongst which 64% were female. Mean age of the total cohort was 45.2 years. The median (interquartile range) time interval between COVID-19 infection and enrolment was 189 [125, 246] days. 83% of participants had at least one persistent symptom, while 96% had positive serology for prior SARS-CoV-2 infection. Late gadolinium enhancement, pericardial effusion, was present in 2.2% and 8.3% respectively, while left ventricular ejection fraction was below the normal reference limit in 17.4% of patients. Von Willebrand factor antigen was elevated in 32.7% of patients and Fibrinogen and D-Dimer levels were found to be elevated in 10.2% and 11.1% of patients, respectively. In a cohort of primary practice patients recently recovered from SARS-CoV-2 infection, prevalence of persistent symptoms and markers of abnormal coagulation were high, despite a lower frequency of abnormalities on CMR compared with prior reports of patients assessed in a hospital setting.Trial Registration: Clinicaltrials.gov, NCT04823182 (prospectively registered on 30th March 2021).


Asunto(s)
Trastornos de la Coagulación Sanguínea , COVID-19 , Cardiopatías , SARS-CoV-2 , Humanos , COVID-19/complicaciones , COVID-19/sangre , Femenino , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Cardiopatías/sangre , Cardiopatías/etiología , Estudios Transversales , SARS-CoV-2/aislamiento & purificación , Trastornos de la Coagulación Sanguínea/etiología , Trastornos de la Coagulación Sanguínea/sangre , Trastornos de la Coagulación Sanguínea/epidemiología , Adulto , Biomarcadores/sangre , Irlanda/epidemiología , Imagen por Resonancia Magnética , Atención Primaria de Salud , Carga Sintomática
3.
Injury ; 55 Suppl 3: 111481, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39300624

RESUMEN

INTRODUCTION: Trauma-induced coagulopathy (TIC) refers to an abnormal coagulation process, an imbalance between coagulation and fibrinolysis due to several pathological factors, such as haemorrhage and tissue injury. Platelet activation and subsequent clot formation are associated with mitochondrial activity, suggesting a possible role for mitochondria in TIC. Comprehensive studies of mitochondrial dysfunction in platelets from severe trauma patients have not yet been performed. METHODS: In this prospective case-control study, patients with severe trauma (ISS≥16) had venous blood samples taken at arrival to the Emergency Unit of a Level 1 Trauma Centre. Mitochondrial functional measurements (Oxygraph-2k, Oroboros) were performed to determine oxygen consumption in different respiratory states, the H2O2 production and extramitochondrial Ca2+ movements. In addition, standard laboratory and coagulation tests, viscoelastometry (ClotPro) and aggregometry (Multiplate) were performed. Measurements data were compared with age and sex matched healthy control patients. RESULTS: Severe trauma patients (n = 113) with a median age of 38 years (IQR, 20-51), a median ISS of 28 (IQR, 20-48) met our inclusion criteria. Oxidative phosphorylation in platelet mitochondria from severe trauma patients significantly decreased compared to controls (34.7 ± 8.8 pmol/s/mL vs. 48.0 ± 19.7 pmol/s/mL). The mitochondrial H2O2 production significantly increased and greater endogenous Ca2+ release was found in the polytrauma group. Consistent with these results, clotting time (CT) increased while maximum clot firmness (MCF) decreased with the EX-test and FIB-test in severe trauma samples. Multiplate aggregometry showed significantly decreased ADP-test (38 ± 12 AUC vs. 112 ± 14 AUC) and ASPI test (78 ± 22 AUC vs. 84 ± 28 AUC) also tended to decrease in mitochondria of polytrauma patients as compared with controls. Significant strong correlation has been demonstrated between mitochondrial OxPhos and MCF while it was negatively correlated with ISS (R2=0.448, P˂0.05), INR, CT and lactate level of patients. CONCLUSIONS: The present study revealed that severe trauma is associated with platelet mitochondrial dysfunction resulting in reduced ATP synthesis and impaired extramitochondrial Ca2+ movement. These factors are required for platelet activation, recruitment and clot stability likely thus, platelet mitochondrial dysfunction contributes to the development of TIC.


Asunto(s)
Trastornos de la Coagulación Sanguínea , Plaquetas , Mitocondrias , Heridas y Lesiones , Humanos , Estudios Prospectivos , Masculino , Estudios de Casos y Controles , Femenino , Adulto , Plaquetas/metabolismo , Heridas y Lesiones/complicaciones , Heridas y Lesiones/sangre , Mitocondrias/metabolismo , Persona de Mediana Edad , Trastornos de la Coagulación Sanguínea/etiología , Trastornos de la Coagulación Sanguínea/sangre , Fosforilación Oxidativa , Coagulación Sanguínea/fisiología , Adulto Joven , Activación Plaquetaria/fisiología , Calcio/metabolismo , Calcio/sangre , Peróxido de Hidrógeno/metabolismo , Peróxido de Hidrógeno/sangre
4.
CNS Neurosci Ther ; 30(9): e70040, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39258827

RESUMEN

BACKGROUND: Nearly half of patients with diabetes experience diabetic peripheral neuropathy (DPN), resulting in a mere 53% survival rate within 3 years. Aberrations in coagulation function have been implicated in the pathogenesis of microvascular complications, prompting the need for a thorough investigation into its role as a contributing factor in the development and progression of DPN. METHODS: Data were gathered from 1211 type 2 diabetes patients admitted to five centers from September 2018 to October 2022 in China. DPN was evaluated by symptoms and electromyography. Motor and sensory nerve conduction velocity (NCV) was appraised and the NCV sum score was calculated for the median, ulnar, and peroneal motor or sensory nerves. RESULTS: Patients with DPN exhibited alterations in coagulation function. (i) Specifically, they exhibited prolonged thrombin time (p = 0.012), elevated fibrinogen (p < 0.001), and shortened activated partial thromboplastin time (APTT; p = 0.026) when compared to the control group. (ii) After accounting for potential confounders in linear regression, fibrinogen, and D-dimer were negatively related to the motor NCV, motor amplitude values, and mean velocity and amplitude. Also, fibrinogen was associated with higher Michigan neuropathy screening instrument (MNSI) scores (ß 0.140; p = 0.001). This result of fibrinogen can be validated in the validation cohort with 317 diabetic patients. (iii) Fibrinogen was independently associated with the risk of DPN (OR 1.172; p = 0.035). In the total age group, DPN occurred at a slower rate until the predicted fibrinogen level reached around 3.75 g/L, after which the risk sharply escalated. CONCLUSIONS: Coagulation function is warranted to be concerned in patients with type 2 diabetes to predict and prevent the occurrence of DPN in clinical practice.


Asunto(s)
Diabetes Mellitus Tipo 2 , Neuropatías Diabéticas , Progresión de la Enfermedad , Conducción Nerviosa , Humanos , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/fisiopatología , Neuropatías Diabéticas/sangre , Neuropatías Diabéticas/fisiopatología , Masculino , Femenino , Persona de Mediana Edad , Anciano , Conducción Nerviosa/fisiología , Trastornos de la Coagulación Sanguínea/etiología , Trastornos de la Coagulación Sanguínea/sangre
5.
Clin Appl Thromb Hemost ; 30: 10760296241280919, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39308431

RESUMEN

BACKGROUND: Coagulopathy is associated with poor prognosis of traumatic brain injury (TBI) patients. This study is performed to explore the association between serum magnesium level and the risk of coagulopathy in TBI. METHODS: TBI patients from the Medical Information Mart for Intensive Care-III database were included for this study. Logistic regression analysis was performed to explore risk factors and develop a predictive model for coagulopathy in TBI. The restricted cubic spline (RCS) was utilized to analyze the association between serum magnesium level and the development of coagulopathy. Receiver operating characteristic curve was drawn to evaluate the performance of the predictive model for coagulopathy. RESULTS: The incidence of coagulopathy in TBI was 32.6%. The RCS indicated the association between magnesium and coagulopathy was U-shaped. Multivariate logistic regression confirmed age, coronary heart disease, cerebral vascular disease, chronic liver disease, GCS, ISS, epidural hematoma, hemoglobin, shock index and magnesium level were independently associated with the coagulopathy in TBI. Compared with patients of magnesium level between 1.7 and 2.3 mg/dL, those with magnesium level below 1.7 mg/dL or above 2.2 mg/dL had a higher risk of coagulopathy. CONCLUSION: Both hypermagnesemia and hypomagnesemia are associated with higher risk of coagulopathy in TBI patients. Physicians should pay more attention on preventing coagulopathy in TBI patients with hypomagnesemia or hypermagnesemia.


Asunto(s)
Trastornos de la Coagulación Sanguínea , Lesiones Traumáticas del Encéfalo , Magnesio , Humanos , Lesiones Traumáticas del Encéfalo/sangre , Lesiones Traumáticas del Encéfalo/complicaciones , Magnesio/sangre , Trastornos de la Coagulación Sanguínea/sangre , Trastornos de la Coagulación Sanguínea/etiología , Femenino , Masculino , Persona de Mediana Edad , Adulto , Factores de Riesgo , Anciano
6.
Curr Med Sci ; 44(5): 912-922, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39285052

RESUMEN

OBJECTIVE: Coagulation abnormalities are common and prognostically significant in intensive care units (ICUs) and are associated with increased mortality. This study aimed to explore the association between the levels of coagulation markers and the risk of mortality among ICU patients with coagulation abnormalities. METHODS: This retrospective study investigated patients with coagulation abnormalities in the ICU between January 2021 and December 2022. The initial point for detecting hemostatic biomarkers due to clinical assessment of coagulation abnormalities was designated day 0. Patients were followed up for 28 days, and multivariate logistic regression analysis was utilized to identify risk factors for mortality. RESULTS: Of the 451 patients analyzed, 115 died, and 336 were alive at the end of the 28-day period. Multivariate analysis revealed that elevated thrombin-antithrombin complex (TAT), tissue plasminogen activator inhibitor complex (tPAIC), prolonged prothrombin time, and thrombocytopenia were independent risk factors for mortality. For nonovert disseminated intravascular coagulation (DIC) patients, older age and thrombocytopenia were associated with increased risks of mortality, whereas elevated levels of plasmin α2-plasmin inhibitor complex (PIC) were found to be independent predictors of survival. In patients with overt DIC, elevated levels of tPAIC were independently associated with increased risks of mortality. Nevertheless, thrombocytopenia was independently associated with increased risks of mortality in patients with pre-DIC. CONCLUSION: Coagulation markers such as the TAT, tPAIC, PIC, and platelet count were significantly associated with mortality, underscoring the importance of maintaining a balance between coagulation and fibrinolysis. These findings highlight the potential for targeted therapeutic interventions based on specific coagulation markers to improve patient outcomes.


Asunto(s)
Trastornos de la Coagulación Sanguínea , Enfermedad Crítica , Unidades de Cuidados Intensivos , Humanos , Masculino , Estudios Retrospectivos , Femenino , Enfermedad Crítica/mortalidad , Factores de Riesgo , Persona de Mediana Edad , Anciano , Trastornos de la Coagulación Sanguínea/mortalidad , Trastornos de la Coagulación Sanguínea/sangre , Biomarcadores/sangre , Coagulación Intravascular Diseminada/mortalidad , Coagulación Intravascular Diseminada/sangre , Antitrombina III , Trombocitopenia/mortalidad , Trombocitopenia/sangre , Péptido Hidrolasas
7.
Eur Surg Res ; 65(1): 115-122, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39348804

RESUMEN

INTRODUCTION: Coagulopathic disorders (CDs) complicate treatment in polytraumatised patients. Against this background, operative strategies for fracture management are controversial in this cohort. This study therefore investigated the effects of two established operative concepts, early total care (ETC) and damage control orthopaedics (DCO), on CD in a large-animal polytrauma (PT) model. METHODS: Twenty-two animals (Sus scrofa domesticus) sustained PT involving blunt-chest trauma, liver laceration, bilateral femur fracture, and pressure-controlled haemorrhagic shock. After resuscitation, animals were allocated to ETC (n = 8), DCO (n = 8), or served as a non-traumatised control group (CG, n = 6). Animals were ventilated and monitored under ICU standards for 72 h. Blood samples were collected at baseline and post-trauma after 1.5, 2.5, 24, 48, and 72 h. Plasminogen activator inhibitor-1 (PAI-1) and thrombin-antithrombin (TAT) complex concentrations were determined by ELISA. RESULTS: Compared to the CG, ETC and DCO subjects had significantly increased plasma concentrations of PAI-1 after 2.5 h (CG vs. ETC: p = 0.0050, CG vs. DCO: p = 0.0016). Furthermore, the ETC group showed significantly increased plasma PAI-1 concentrations after 24 h compared to the CG and DCO groups (CG vs. ETC: p = 0.0002, DCO vs. ETC: p = 0.0004). During the later clinical course, concentrations of TAT were significantly increased in the ETC group compared to the CG and DCO group after 72 h (CG vs. ETC: p = 0.0290, DCO vs. ETC: p = 0.0322). CONCLUSION: PT is strongly associated with CD in the early post-traumatic course. In comparison to DCO, ETC appeared to be negatively associated with CD. Future studies must investigate this impact, especially in those patients admitted with trauma-induced coagulopathy, to improve outcomes.


Asunto(s)
Trastornos de la Coagulación Sanguínea , Modelos Animales de Enfermedad , Traumatismo Múltiple , Animales , Traumatismo Múltiple/complicaciones , Trastornos de la Coagulación Sanguínea/etiología , Trastornos de la Coagulación Sanguínea/sangre , Porcinos , Inhibidor 1 de Activador Plasminogénico/sangre , Antitrombina III , Procedimientos Ortopédicos/efectos adversos , Masculino , Péptido Hidrolasas
8.
Thromb Res ; 243: 109152, 2024 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-39288599

RESUMEN

INTRODUCTION: Sepsis-induced coagulopathy (SIC) is a severe complication of sepsis, characterized by poor prognosis and high mortality. However, the predictors of SIC in pediatric patients have yet to be identified. Our aim was to develop a user-friendly and efficient nomogram for predicting SIC in sepsis patients admitted to the pediatric intensive care unit (PICU). MATERIALS AND METHODS: We screened 948 sepsis patients admitted to the PICU in three hospitals located in Shandong, China. Least absolute shrinkage and selector operation (LASSO) regression was used in the training cohort for variable selection and regularization. The selected variables were utilized to construct a nomogram for predicting the risk of SIC among sepsis patients admitted to the PICU. RESULTS: Overall, SIC was observed in 324 (40.3 %) patients. The morbidity of SIC in sepsis patients is associated with age, fibrinogen, prothrombin time, C-reactive protein, lactate and the pediatric sequential organ failure assessment score. We developed a nomogram for the early identification of SIC in the training cohort (area under the curve [AUC] 0.869, 95 % confidence interval [CI] 0.830-0.907, sensitivity 75.7 %, specificity 84.8 %) and validation cohorts (validation cohort 1: AUC 0.854, 95 % CI 0.805-0.903, sensitivity 72.0 %, specificity 86.9 %; validation cohort 2: AUC 0.853, 95 % CI 0.796-0.910, sensitivity 70.1 %, specificity 87.8 %). The calibration plots of the nomogram demonstrated a high level of concordance in the SIC probabilities between the observed and predicted values. CONCLUSIONS: The novel nomogram showed excellent predictive performance for the morbidity of SIC among sepsis patients admitted to the PICU, potentially assisting healthcare professionals in early identification and intervention for SIC.


Asunto(s)
Trastornos de la Coagulación Sanguínea , Unidades de Cuidado Intensivo Pediátrico , Nomogramas , Sepsis , Humanos , Estudios Retrospectivos , Masculino , Femenino , Sepsis/sangre , Sepsis/complicaciones , Unidades de Cuidado Intensivo Pediátrico/estadística & datos numéricos , Preescolar , Niño , Trastornos de la Coagulación Sanguínea/sangre , Trastornos de la Coagulación Sanguínea/diagnóstico , Trastornos de la Coagulación Sanguínea/etiología , Lactante
9.
J Cardiothorac Vasc Anesth ; 38(10): 2368-2376, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39129096

RESUMEN

OBJECTIVES: Perioperative coagulation management in liver transplantation recipients is challenging. Viscoelastic testing with rotational thromboelastography (TEG) can help quantify hemostatic profiles. The current work aimed to investigate whether the etiology of end-stage liver disease, pretransplant disease severity, or pretransplant thrombotic or bleeding complications are associated with specific TEG patterns. DESIGN: Retrospective cohort study. SETTING: Single quaternary care hospital. PARTICIPANTS: A total of 1,078 adult liver transplant patients. INTERVENTIONS: The primary exposure was the etiology of end-stage liver disease classified as either intrinsic or nonintrinsic (eg, biliary obstruction or cardiovascular). Secondary exposures were patients' preoperative Model for End-Stage Liver Disease (MELD) score, Child-Pugh class, presence of major preoperative thrombotic complications, and major bleeding complications. MEASUREMENTS AND MAIN RESULTS: Patients with intrinsic liver disease (84%) showed higher odds of hypocoagulable (odds ratio [OR]: 3.70, 95% confidence interval [CI]: 1.94-7.07, p < 0.0001) and mixed TEG patterns (OR: 4.59, 95% CI: 2.07-10.16, p = 0.0002) compared with those with nonintrinsic disease. Increasing MELD scores correlated with higher odds of hypocoagulable (OR: 1.14, 95% CI: 1.08-1.19, p < 0.0001) and mixed TEG patterns (OR: 1.08, 95% CI: 1.03-1.14, p = 0.0036). Child-Pugh class C was associated with higher odds of hypocoagulable (OR: 8.55, 95% CI: 3.26-22.42, p < 0.0001) and mixed patterns (OR: 12.48, 95% CI: 3.89-40.03, p < 0.0001). Major preoperative thrombotic complications were not associated with specific TEG patterns, although an interaction with liver disease severity was observed. CONCLUSIONS: Liver transplantation candidates with intrinsic liver disease tend to exhibit hypocoagulable TEG patterns, while nonintrinsic disease is associated with hypercoagulability. Increasing end-stage liver disease severity, as evidenced by increasing MELD scores and higher Child-Pugh classification, was also associated with hypocoagulable TEG patterns.


Asunto(s)
Enfermedad Hepática en Estado Terminal , Trasplante de Hígado , Tromboelastografía , Humanos , Tromboelastografía/métodos , Estudios Retrospectivos , Trasplante de Hígado/efectos adversos , Masculino , Enfermedad Hepática en Estado Terminal/cirugía , Enfermedad Hepática en Estado Terminal/sangre , Enfermedad Hepática en Estado Terminal/complicaciones , Femenino , Persona de Mediana Edad , Estudios de Cohortes , Coagulación Sanguínea/fisiología , Adulto , Anciano , Trastornos de la Coagulación Sanguínea/etiología , Trastornos de la Coagulación Sanguínea/diagnóstico , Trastornos de la Coagulación Sanguínea/sangre , Trastornos de la Coagulación Sanguínea/epidemiología
10.
J Thromb Haemost ; 22(11): 3059-3069, 2024 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-39151703

RESUMEN

BACKGROUND: Vitamin K (VK) deficiency (VKD) impairs γ-carboxylation of VK-dependent factors (VKDFs), resulting in higher factor (F)II levels measured by Ecarin (FIIE) reagents (that convert des-γ-carboxylated FII to meizothrombin) than by prothrombin time (FII) reagents. OBJECTIVES: To evaluate FII/FIIE abnormalities among patients assessed for coagulopathies and identify findings predictive of coagulopathy improvement after VK. METHODS: We retrospectively assessed consecutive cases from 2002 to 2021 with FII/FIIE tests and the sensitivity and specificity of FII/FIIE ratios and FIIE-FII differences for VKD defined as international normalized ratio correction/improvement of ≥0.5 after VK. RESULTS: Two hundred ninety-two patients (males, 58.2%; adults, 85.6%; median age, 73 years) were evaluated (84.2% hospitalized, 48.3% in intensive care, 71.6% with active liver disease, and 28% deceased at discharge) and 25% to 38% had FII/FIIE findings suggestive of VKD. Among 170 patients assessed for response to VK, FII/FIIE ratios of ≤0.84 to 0.91 and FIIE-FII differences of >0.04 U/mL had similar modest sensitivity (47.7%-69.3%) and modest to good specificity (67.1%-91.5%) for VKD. FII/FIIE ratios of <0.86, suggestive of VKD (sensitivity, 47.7%; specificity, 90.2%), were more common in patients deficient in only VKDF (P = .0001), but were detected in 16% with non-VKDF deficiencies. Low FIIE was commonly associated with active liver disease (P = .0002). Patients with and without probable VKD (based on FII/FIIE ratios of <0.86) had similar mortality, bleeding, and rates of prothrombin complex concentrate and red cell transfusions (P ≥ .78), but fewer with probable VKD received plasma and fibrinogen replacement (P ≤ .024). CONCLUSION: FII/FIIE comparison aids the diagnosis of VKD and predicts clinical responses to VK treatment among patients with coagulopathies.


Asunto(s)
Tiempo de Protrombina , Protrombina , Deficiencia de Vitamina K , Humanos , Masculino , Femenino , Estudios Retrospectivos , Anciano , Persona de Mediana Edad , Deficiencia de Vitamina K/sangre , Deficiencia de Vitamina K/diagnóstico , Deficiencia de Vitamina K/complicaciones , Anciano de 80 o más Años , Trastornos de la Coagulación Sanguínea/diagnóstico , Trastornos de la Coagulación Sanguínea/sangre , Valor Predictivo de las Pruebas , Coagulación Sanguínea/efectos de los fármacos , Relación Normalizada Internacional , Adulto , Indicadores y Reactivos , Vitamina K , Factores de Tiempo , Reproducibilidad de los Resultados
11.
J Thromb Haemost ; 22(11): 3048-3058, 2024 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-39128655

RESUMEN

BACKGROUND: Preoperative identification of patients with hemostasis abnormalities leading to an increased bleeding risk is based on routine hemostasis tests: prothrombin time (PT), activated partial thromboplastin time (APTT), and platelet count. Because of their low predictive performance, guidelines recommend replacing them with structured bleeding risk questionnaires, but none is validated in this population. OBJECTIVES: To assess the diagnostic accuracy of 3 strategies, performed at the preanesthesia visit before scheduled interventions, and to identify patients with hemostasis abnormalities leading to an increased bleeding risk METHODS: A multicenter study was performed in 7 French academic hospitals, involving patients scheduled for surgical intervention, without antiplatelet/anticoagulant treatment. The 3 strategies consisted of 1-a structured screening questionnaire; 2-PT, APTT, and platelet count ordered in selected patients; and 3-systematic PT, APTT, and platelet count. The reference standard comprised von Willebrand factor activity/antigen, factor (F)VIII, FIX, FXI, platelet function analyzer, and, when required, FII, FV, FX, and FVII and hemostasis consultation. RESULTS: Eighteen (1.2%) of 1484 patients had a hemostasis abnormality leading to an increased bleeding risk according to reference standard. In the overall cohort, sensitivity of the questionnaire-based strategy was 50% (95% CI, 26%-74%; specificity, 87% [95% CI, 85%-88%]); sensitivity was 0% (95% CI, 0%-41%) in men vs 82% (95% CI, 48%-98%) in women. For selective routine tests, sensitivity was 33% (95% CI, 13%-59%) and specificity 97% (95% CI, 96%-98%). Corresponding values for systematic routine tests were 44% (95% CI, 22%-69%) and 93% (95% CI, 91%-94%). CONCLUSION: Sensitivity was low for all 3 strategies investigated. The structured screening questionnaire had clinically acceptable diagnostic accuracy only in women.


Asunto(s)
Hemorragia , Hemostasis , Tiempo de Protrombina , Humanos , Femenino , Masculino , Persona de Mediana Edad , Encuestas y Cuestionarios , Anciano , Tiempo de Tromboplastina Parcial , Hemorragia/diagnóstico , Hemorragia/sangre , Recuento de Plaquetas , Medición de Riesgo , Factores de Riesgo , Valor Predictivo de las Pruebas , Francia , Adulto , Reproducibilidad de los Resultados , Trastornos de la Coagulación Sanguínea/diagnóstico , Trastornos de la Coagulación Sanguínea/sangre , Cuidados Preoperatorios , Pruebas de Coagulación Sanguínea , Coagulación Sanguínea/efectos de los fármacos , Sensibilidad y Especificidad , Estudios Prospectivos
12.
Clin Lab Med ; 44(3): 527-539, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39089756

RESUMEN

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.


Asunto(s)
Tiempo de Protrombina , Humanos , Pruebas de Coagulación Sanguínea , Coagulación Sanguínea , Tiempo de Tromboplastina Parcial , Trastornos de la Coagulación Sanguínea/diagnóstico , Trastornos de la Coagulación Sanguínea/sangre , Productos de Degradación de Fibrina-Fibrinógeno/análisis
13.
Scand J Trauma Resusc Emerg Med ; 32(1): 71, 2024 Aug 19.
Artículo en Inglés | MEDLINE | ID: mdl-39160625

RESUMEN

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.


Asunto(s)
Trastornos de la Coagulación Sanguínea , Puntaje de Gravedad del Traumatismo , Fenotipo , Heridas y Lesiones , Humanos , Masculino , Femenino , Trastornos de la Coagulación Sanguínea/etiología , Trastornos de la Coagulación Sanguínea/sangre , Adulto , Persona de Mediana Edad , Heridas y Lesiones/complicaciones , Heridas y Lesiones/sangre , Biomarcadores/sangre , Endotelio Vascular/fisiopatología , Endotelio Vascular/lesiones , Europa (Continente)/epidemiología
14.
Hamostaseologie ; 44(5): 358-367, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-38950624

RESUMEN

Bleeding disorder of unknown cause (BDUC) is a diagnosis of exclusion after exhaustive evaluation of plasmatic coagulation and platelet function. This review explores the utility of global hemostatic assays as confirmatory tests and in elucidating the pathophysiology of BDUC. Unlike traditional hemostatic tests that focus on coagulation factors, global assays are conducted both in plasma and also whole blood. These assays provide a more comprehensive understanding of the cell-based model of coagulation, aid in the identification of plasmatic factor abnormalities that may reduce hemostatic capacity, and allow for the assessment of impaired platelet-endothelial interactions under shear stress, as well as hyperfibrinolytic states. While clinical tests such as skin bleeding time and global assays such as PFA-100 exhibit limited diagnostic capacity, the role of viscoelastic testing in identifying hemostatic dysfunction in patients with BDUC remains unclear. Thrombin generation assays have shown variable results in BDUC patients; some studies demonstrate differences compared with healthy controls or reference values, whereas others question its clinical utility. Fibrinolysis assessment in vitro remains challenging, with studies employing euglobulin clot lysis time, plasma clot lysis time, and fluorogenic plasmin generation yielding inconclusive or conflicting results. Notably, recent studies suggest that microfluidic analysis unveils shear-dependent platelet function defects in BDUC patients, undetected by conventional platelet function assays. Overall, global assays might be helpful for exploring underlying hemostatic impairments, when conventional hemostatic laboratory tests yield no results. However, due to limited data and/or discrepant results, further research is needed to evaluate the utility of global assays as screening tools.


Asunto(s)
Hemostasis , Humanos , Hemostasis/fisiología , Pruebas de Coagulación Sanguínea/métodos , Trastornos Hemorrágicos/sangre , Trastornos Hemorrágicos/diagnóstico , Pruebas de Función Plaquetaria/métodos , Trastornos de la Coagulación Sanguínea/sangre , Trastornos de la Coagulación Sanguínea/diagnóstico
15.
PLoS One ; 19(7): e0304231, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38985805

RESUMEN

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.


Asunto(s)
Plaquetas , Hemostasis , Microfluídica , Heridas y Lesiones , Humanos , Plaquetas/metabolismo , Masculino , Femenino , Adulto , Heridas y Lesiones/sangre , Heridas y Lesiones/complicaciones , Microfluídica/métodos , Persona de Mediana Edad , Trastornos de la Coagulación Sanguínea/etiología , Trastornos de la Coagulación Sanguínea/sangre , Factor de von Willebrand/metabolismo , Fibrinógeno/metabolismo , Estudios de Casos y Controles , Tiempo de Sangría
16.
Int J Mol Sci ; 25(14)2024 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-39063005

RESUMEN

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.


Asunto(s)
Plaquetas , Lesiones Traumáticas del Encéfalo , Humanos , Lesiones Traumáticas del Encéfalo/mortalidad , Lesiones Traumáticas del Encéfalo/sangre , Lesiones Traumáticas del Encéfalo/complicaciones , Lesiones Traumáticas del Encéfalo/fisiopatología , Masculino , Femenino , Persona de Mediana Edad , Adulto , Plaquetas/metabolismo , Estudios Retrospectivos , Tromboelastografía , Anciano , Pronóstico , Biomarcadores/sangre , Trastornos de la Coagulación Sanguínea/etiología , Trastornos de la Coagulación Sanguínea/mortalidad , Trastornos de la Coagulación Sanguínea/sangre
17.
Mol Genet Metab ; 142(4): 108530, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38968673

RESUMEN

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.


Asunto(s)
Trastornos de la Coagulación Sanguínea , Trastornos Congénitos de Glicosilación , Fosfoglucomutasa , Humanos , Trastornos Congénitos de Glicosilación/genética , Trastornos Congénitos de Glicosilación/complicaciones , Trastornos Congénitos de Glicosilación/patología , Fosfoglucomutasa/genética , Fosfoglucomutasa/deficiencia , Masculino , Femenino , Estudios Retrospectivos , Trastornos de la Coagulación Sanguínea/genética , Trastornos de la Coagulación Sanguínea/sangre , Lactante , Preescolar , Niño , Adolescente , Galactosa , Adulto , Adulto Joven , Glicosilación , Recién Nacido , Coagulación Sanguínea/genética
18.
J Infect Dev Ctries ; 18(5): 666-671, 2024 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-38865388

RESUMEN

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.


Asunto(s)
Trastornos de la Coagulación Sanguínea , COVID-19 , Productos de Degradación de Fibrina-Fibrinógeno , Valor Predictivo de las Pruebas , Humanos , COVID-19/sangre , COVID-19/diagnóstico , COVID-19/complicaciones , Productos de Degradación de Fibrina-Fibrinógeno/análisis , Masculino , Femenino , Persona de Mediana Edad , Tiempo de Tromboplastina Parcial , Trastornos de la Coagulación Sanguínea/diagnóstico , Trastornos de la Coagulación Sanguínea/sangre , Adulto , Anciano , Índice de Severidad de la Enfermedad , SARS-CoV-2/aislamiento & purificación
19.
Adv Gerontol ; 37(1-2): 149-152, 2024.
Artículo en Ruso | MEDLINE | ID: mdl-38944786

RESUMEN

In the treatment of coronavirus infections, it is important not only to understand the course of the disease, but also to understand what is happening in the human body, especially in the circulatory system, that is, which disorders lead to deterioration and further complications. Hemostasis disorder in COVID-19 plays an important role in the etiology and clinical manifestations of the disease. The ability to identify factors and risk groups for the development of thrombotic complications, the ability to dynamically interpret peripheral blood parameters and coagulograms, knowledge of diagnostic criteria for possible hemostasis disorders (for example, DIC syndrome, sepsis-associated coagulopathy, antiphospholipids, hemophagocytosis and hypercoagulation syndrome) are necessary to determine the indications for the test. Differentiated prescribing of clinically justified therapy (including anticoagulants and blood components) is important, which determines the complexity of treatment and prognosis for patients with COVID-19. This article is a review of the literature on the topic of hemostasis disorders in elderly and senile patients with mesenteric thrombosis in COVID 19 over the past few years.


Asunto(s)
COVID-19 , SARS-CoV-2 , Trombosis , Humanos , COVID-19/complicaciones , COVID-19/fisiopatología , Anciano , Trombosis/etiología , Trombosis/diagnóstico , Trombosis/sangre , Trastornos de la Coagulación Sanguínea/etiología , Trastornos de la Coagulación Sanguínea/diagnóstico , Trastornos de la Coagulación Sanguínea/sangre , Hemostasis/fisiología , Anticoagulantes/uso terapéutico , Anticoagulantes/administración & dosificación
20.
Burns ; 50(7): 1769-1778, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38902134

RESUMEN

BACKGROUND: In the days following a burn injury, major burn patients (MBP) present a multifactorial coagulation disorder known as acute burn-induced coagulopathy. Several studies have investigated coagulation in MBPs; however, Factor XIII (FXIII), which converts fibrin monomers into a stable clot and promotes wound healing, has not yet been studied. OBJECTIVE: To determine the kinetics of FXIII and other coagulation factors and cofactors in MBPs in order to clarify coagulopathy in these patients and its potential relationship with surgical bleeding. METHODS: Prospective observational pilot study of the kinetics of FXIII and other coagulation factors and cofactors in MBPs during the first 30 days of burn injury. RESULTS: FXIII levels show a significant decline of 75.10% in the interval between the burn injury and surgery, and a decline of 87.70% in the 24 h following surgery. Patients undergo surgery with a median antigenic FXIII of 32%. Plasma levels of most factors decrease significantly 24 h after the burn injury. CONCLUSION: MBPs experience a significant decrease in plasma levels of FXIII from the time of admission up to 24 h after surgery. Abnormally low levels were observed at the time of surgery that could not be detected by other coagulation tests. The decrease in most factors at 24 h seems to be associated with dilution due to intensive fluid resuscitation.


Asunto(s)
Trastornos de la Coagulación Sanguínea , Quemaduras , Factor XIII , Quemaduras/sangre , Quemaduras/metabolismo , Quemaduras/complicaciones , Humanos , Masculino , Adulto , Femenino , Persona de Mediana Edad , Factor XIII/metabolismo , Estudios Prospectivos , Proyectos Piloto , Trastornos de la Coagulación Sanguínea/etiología , Trastornos de la Coagulación Sanguínea/sangre , Anciano , Adulto Joven , Coagulación Sanguínea/fisiología
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