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During the coronavirus disease 2019 (COVID-19) pandemic, clinical staff learned how to manage patients enduring extended stays in an intensive care unit (ICU). COVID-19 patients requiring critical care in an ICU face a high risk of experiencing prolonged intensive care (PIC). The use of invasive mechanical ventilation in individuals with severe acute respiratory distress syndrome can cause numerous complications that influence both short-term and long-term morbidity and mortality. Those risks underscore the importance of proactively addressing functional complications. Mitigating secondary complications unrelated to the primary pathology of admission is imperative in minimizing the risk of PIC. Therefore, incorporating strategies to do that into daily ICU practice for both COVID-19 patients and those critically ill from other conditions is significantly important.
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Transfusion of blood products in orthotopic liver transplantation (OLT) significantly increases post-transplant morbidity and mortality and is associated with reduced graft survival. Based on these results, an active effort to prevent and minimize blood transfusion is required. Patient blood management is a revolutionary approach defined as a patient-centered, systematic, evidence-based approach to improve patient outcomes by managing and preserving a patient's own blood while promoting patient safety and empowerment. This approach is based on three pillars of treatment: (1) detecting and correcting anemia and thrombocytopenia, (2) minimizing iatrogenic blood loss, detecting, and correcting coagulopathy, and (3) harnessing and increasing anemia tolerance. This review emphasizes the importance of the three-pillar nine-field matrix of patient blood management to improve patient outcomes in liver transplant recipients.
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Since the report of the first case of COVID-19 in Wuhan, China, on December 31, 2019, several associated thrombotic complications have been reported, mainly venous thromboembolic events, and myocardial infarctions, in addition to peripheral arterial thrombosis and cerebral vascular events, which have been attributed to a hypercoagulable state. We aimed to know the prevalence and prognostic biomarkers in patients with pulmonary thromboembolism (PE) and SARS Cov-2 pneumonia. Hospitalized patients with SARS Cov-2 pneumonia who have had clinical, biomarker, and imaging data (chest angiography) of pulmonary thromboembolism were included. Descriptive statistics and prevalence rates were calculated. For the analysis between the groups, the paired Student's t and the Wilcoxon test were performed. CT angiography was performed on 26 patients at our institution, with a diagnosis of severe pneumonia secondary to SARS-CoV2. 9 of the patients (34.6%) had a venous thromboembolic disease. Type 2 DM was the most frequent comorbidity up to 55.5% of the total; it was followed by obesity and overweight in 55.5%, and in third place, by systemic arterial hypertension in 33.3% of the cases, 1 (11.1%) patient had chronic kidney disease and 1 (11.1%) patient with a history of cancer, only 1 patient met criteria and was treated with thrombolysis. 6 (66.6%) of the patients had segmental PE, 3 (33.3%) patients had subsegmental PE, and 4 (44.4%) patients presented pulmonary infarction.
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COVID-19 , Embolia Pulmonar , Tromboembolia Venosa , Trombose Venosa , Humanos , COVID-19/complicações , COVID-19/epidemiologia , Hospitais , Prevalência , Embolia Pulmonar/epidemiologia , Embolia Pulmonar/etiologia , RNA Viral , SARS-CoV-2 , Tromboembolia Venosa/epidemiologiaRESUMO
Background: The use of convalescent plasma (CP) has been considered for its immunological mechanisms that could benefit patients in moderate and severe stages of COVID-19. This study evaluated the safety and efficacy of the use of donor CP for COVID-19. Material and methods: A double-blind, randomized controlled clinical trial was conducted from May to October 2020. Thirty-nine participants with moderate (II) and severe (III) stages of COVID-19 confirmed by RT-PCR were included. The study randomization rate was set at 3:1. CPs were chosen for application with a neutralizing antibody titer of ≥1:32. Results: We observed a significantly lower 21-day post-transfusion mortality HR: 0.17 (95.0% CI [0.07−0.45, p < 0.001]) in the group receiving CP compared with the control group; protective units (PU) in the group receiving convalescent plasma after seven days were significantly higher (512 (32−16,384) vs. 96 (32−256), p = 0.01); the PAO2/FIO2 index showed a significant improvement in the group receiving CP (251.01 (109.4) vs. 109.2 (62.4), p < 0.001, in the control group). Conclusion: CP is safe and effective, as it decreased mortality in the CP group compared with the control group.
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Resumen: La tromboelastometría evalúa los cambios viscoelásticos en el proceso de coagulación. Nos ofrece una representación gráfica de la formación del coágulo, la estabilidad del mismo y la presencia de lisis. La tromboelastometría rotacional es una herramienta diagnóstica que representa de forma gráfica la funcionalidad del coágulo para un manejo dirigido e individualizado de la coagulopatía asociada a hemorragia. En este trabajo se puntualiza cómo la tromboelastometría rotacional es a la coagulación como el electrocardiograma es al corazón.
Abstract: Thromboelastometry evaluates viscoelastic changes in the coagulation process. It offers us a graphic representation of the formation of the clot, its stability and the presence of lysis. Rotational thromboelastometry is a diagnostic tool that graphs the functionality of the clot, for a targeted and individualized management of bleeding-associated coagulopathy. In this work it is specified how rotational thromboelastometry is to coagulation as the electrocardiogram is to the heart.
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A proof-of-concept study using thrombolysis with catheter-directed tissue plasminogen activator (tPA) and pulmonary angiography imaging was performed to visualize perfusion deficits and reperfusion/therapeutic effects of tPA. DESIGN: A prospective, open-label, compassionate study. Descriptive statistics were presented for categorical variables and as means with sds for continuous variables. The Wilcoxon test was used to determine the differences between the two-related samples and a t test for continuous variables. Statistical significance was set at p value of less than 0.05. Agreement between observations was evaluated using the Kappa Cohen index and overall agreement using the Fleiss Kappa coefficient. SETTING: A single COVID-19 ICU of Mexico´s General Hospital Dr Eduardo Liceaga. SUBJECTS: Fifteen patients with severe Delta variant severe acute respiratory syndrome coronavirus 2 infection, 18-75 years old, requiring mechanical ventilation with a persistent Fio2 requirement of 70% or higher and Pao2/Fio2 ratio (or imputed ratio) less than 150 for more than 4 hours. The coagulation inclusion criteria were International Society on Thrombosis and Haemostasis score greater than 5, and presence of a d-dimer greater than 1,200, with viscoelastic testing using rotational thromboelastometry (Instrumentation Laboratories, Mexico City, Mexico) showing both hypercoagulability (EXTEM amplitude at 5 min > 65 FIBTEM > 30) and hypofibrinolysis (EXTEM maximum lysis < 8%). INTERVENTIONS: Catheter-directed tPA angiography and iFlow system analysis to assess pre-tPA baseline pulmonary perfusion and changes in response to thrombolysis. RESULTS: Nine patients had microvascular filling defects demonstrated by angiography, and good agreement was found with iFlow analysis (Æ = 0.714). Statistically significant differences were identified in the area under the curve (AUC) region of interest/AUC reference tissue with and without filling defects in phase 2 DM -0.09206 (sd ± 0.16684) (p = 0.003). The Pao2/Fio2 values measured immediately and 48 hours after the procedure were significantly higher (p = 0.001 and p = 0.005, respectively). Statistically significant differences were found in d-dimer values (p = 0.007), Fio2 (p = 0.002), and oxygen saturation in arterial blood/Fio2 (p = 0.045), as well as in the number of patients who required prone positioning before, immediately after the procedure, and at 48 hours after the procedure (p = 0.002). CONCLUSIONS: Thrombolysis with catheter-directed tPA resulted in imaging evidence via pulmonary angiography and iFlow technology of improved lung perfusion in COVID-19 patients with severe respiratory failure.
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BACKGROUND AND OBJECTIVE: The use of fibrinogen concentrate to treat or prevent major bleeding with regard to potential adverse reactions has not been free of controversy. Our objective was to perform a post-authorization safety study to describe the use of Clottafact® (LFB Biomedicaments) fibrinogen concentrate in real-life medical practice in Mexico. METHODS: This was a prospective, observational study that collected and evaluated information between January 2017 and June 2019 related to suspected serious adverse reactions (SUSARs) during and after Clottafact® infusion. RESULTS: Information from 40 subjects was analyzed; 43% were women (n = 17), mean age was 39.05 ± 26.8 years (range 0-91 years). The medical specialties included in this analysis were cardiac surgery - 52.5% of the cases, gynecology/obstetrics - 17.5%, general surgery and orthopedics - 12.5% each, and hematology and neurosurgery - 2.5%, respectively. Mean plasma fibrinogen levels before and after Clottafact® infusion were 2.58 g/L and 4.02 g/L; p = 0.001, respectively. The mean Clottafact® dose was 2.20 ± 0.77 g. One patient presented SUSARs (dry mouth and dysgeusia) with drug administration, which ceased after treatment discontinuation. CONCLUSIONS: In this real-life post-marketing study, the safety profile of Clottafact® was very similar to previous reports. Thus, Clottafact® shows a favorable safety profile in clinical practice.
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Fibrinogênio/uso terapêutico , Hemorragia/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Fibrinogênio/efeitos adversos , Hemostáticos , Humanos , Lactente , Recém-Nascido , Masculino , México , Pessoa de Meia-Idade , Gravidez , Estudos Prospectivos , Adulto JovemRESUMO
There is currently a lack of universally accepted criteria for gastrointestinal (GI) failure or dysfunction in critical care. Moreover, the clinical assessment of intestinal function is notoriously difficult and thus often goes unrecognized, contributing to poor outcomes. A recent grading system has been proposed to define acute gastrointestinal injury (AGI) in conjunction with other organ function scores (e.g., SOFA). Ultrasonography has become widely accepted as a diagnostic tool for GI problems and pathology. We propose a sonographic examination of the abdomen, using the GUTS protocol (gastrointestinal and urinary tract sonography) in critically ill patients as part of the point-of-care ultrasound evaluation in patients with AGI. This article reviews possible applications of ultrasonography that may be relevant to monitor the GI function in critically ill patients. The GI ultrasound protocol (GUTS) focuses on four gastrointestinal endpoints: gastrointestinal diameter, mucosal thickness, peristalsis, and blood flow. Moreover, it is possible to examine the urinary tract and kidney function. Real-time ultrasound with the GUTS protocol is a simple, inexpensive, bedside imaging technique that can provide anatomical and functional information of the GI tract. Further studies are needed to investigate the utility of GUTS with other parameters, such as GI biomarkers, AGI class, and clinical outcomes.
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Estado Terminal/terapia , Trato Gastrointestinal/diagnóstico por imagem , Trato Gastrointestinal/fisiopatologia , Sistemas Automatizados de Assistência Junto ao Leito , Ultrassonografia , Sistema Urinário/diagnóstico por imagem , Abdome/diagnóstico por imagem , HumanosRESUMO
Resumen: El embarazo es un estado que impone un verdadero desafío para el sistema cardiovascular materno. Las pacientes obstétricas que se complican con preeclampsia, enfermedad cardiaca, sepsis, hemorragia y tromboembolia pulmonar, se caracterizan por profundas alteraciones hemodinámicas, las cuales representan las principales causas de morbilidad y mortalidad materna extrema, por lo que existe la necesidad de una correcta evaluación y monitoreo validado de estos parámetros en este tipo de pacientes. El objetivo de esta revisión es describir la tecnología disponible a la cabecera del enfermo para la implementación de este monitoreo hemodinámico en la paciente embarazada de alto riesgo.
Abstract: Pregnancy is a state, which poses a real challenge to the maternal cardiovascular system. Obstetric patients who are complicated by preeclampsia, heart disease, sepsis, hemorrhage and pulmonary thromboembolism are characterized by profound hemodynamic alterations, which represent the main causes of morbidity and extreme maternal mortality, so there is a need for a correct evaluation and monitoring of these parameters, which is validated in this type of patients. The objective of this review is to describe the technology available at the patient's bedside for the performance of this hemodynamic monitoring in the high-risk pregnant patient.
Resumo: A gravidez é um estado que representa um verdadeiro desafio para o sistema cardiovascular materno. A paciente obstétrica que apresenta complicações como pré-eclâmpsia, doenças cardíacas, sepse, hemorragia e tromboembolismo pulmonar, se caracterizam por profundas alterações hemodinâmicas que representam as principais causas de morbimortalidade materna extrema, por isso é necessária uma avaliação correta e a monitorização desses parâmetros, que esteja validado nesse tipo de pacientes. O objetivo desta revisão é descrever a tecnologia disponível à beira do leito para a realização da monitorização hemodinâmica na paciente obstétrica de alto risco.
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Resumen: El síndrome de insuficiencia respiratoria aguda engloba una constelación relativamente uniforme de características clínicas, radiológicas y fisiológicas en pacientes con falla respiratoria de inicio rápido. En la actualidad existen expertos que consideran la necesidad de denominar a este síndrome lesión alveolar difusa debido a sus reportes histopatológicos. El objetivo de este trabajo de revisión es dar a conocer los cambios histopatológicos de los pacientes con síndrome de insuficiencia respiratoria aguda y la relación que existe con las clasificaciones clínicas actuales.
Abstract: The acute respiratory distress syndrome, includes a relatively uniform radiological and physiological constellation of clinical features respiratory failure in patients with quick start. At present there are experts who consider the need to call this syndrome Diffuse alveolar injury, by histopathological reports this. The objective of this review paper is to make known the histopathologic changes of patients with acute respiratory distress syndrome and the relationship with current clinical classifications.
Resumo: A síndrome da angústia respiratória aguda (SARA) engloba uma constelação relativamente uniforme de características clínicas, radiológicas e fisiológicas em pacientes com falha respiratória de início rápido. Atualmente, existem especialistas que consideram a necessidade de chamar essa síndrome de Lesão Alveolar Difusa pelos relatórios de histopatologia desta. O objetivo deste artigo de revisão é aumentar a consciência das alterações histopatológicas dos pacientes com SARA e a relação com as classificações clínicas atuais.
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BACKGROUND: Metabolic changes of glucose in critically ill patients increase morbidity and mortality. The appropriate level of blood glucose has not been established so far and should be adjusted for different populations. However concepts such as glucose variability and relative hypoglycemia of critically ill patients are concepts that are changing management methods and achieving closer monitoring. OBJECTIVES: The purpose of this review is to present new data about the management and metabolic control of patients in critical areas. CONCLUSIONS: Currently glucose can no longer be regarded as an innocent element in critical patients; both hyperglycemia and hypoglycemia increase morbidity and mortality of patients. Protocols and better instruments for continuous measurement are necessary to achieve the metabolic control of our patients.
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Cuidados Críticos/métodos , Estado Terminal/terapia , Hiperglicemia/tratamento farmacológico , Hipoglicemia/tratamento farmacológico , Adaptação Fisiológica , Glicemia/análise , Ensaios Clínicos como Assunto , Gerenciamento Clínico , Metabolismo Energético , Gluconeogênese , Hormônios/metabolismo , Humanos , Hiperglicemia/epidemiologia , Hiperglicemia/etiologia , Hiperglicemia/fisiopatologia , Hipoglicemia/epidemiologia , Hipoglicemia/etiologia , Hipoglicemia/fisiopatologia , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/efeitos adversos , Hipoglicemiantes/uso terapêutico , Insulina/administração & dosagem , Insulina/efeitos adversos , Insulina/uso terapêutico , Estudos Multicêntricos como Assunto , Insuficiência de Múltiplos Órgãos/etiologia , Insuficiência de Múltiplos Órgãos/prevenção & controleRESUMO
Resumen: Objetivo: Comprobar la capacidad pronóstica como predictor de mortalidad de la clasificación de Child-Pugh lactato en la población de pacientes cirróticos que ingresan en la Unidad de Cuidados Intensivos de la Fundación Clínica Médica Sur. Material y métodos: Estudio de investigación clínica, cohorte no concurrente, donde se obtuvieron datos en el periodo comprendido del 1 de enero de 2012 al 31 de diciembre de 2014. Resultados: Ingresaron 28 casos a la Unidad de Terapia Intensiva de la Fundación Clínica Médica Sur con diagnóstico de cirrosis hepática; de ellos, fallecieron un total de 16 (57.1%) sujetos dentro de los primeros 40 días posteriores a su ingreso y sobrevivieron 12 (42.9%). Se calculó si existía correlación entre la defunción y el puntaje de la clasificación Child-Pugh lactato mayor de 14, y se encontró una r = 0.708. El puntaje mayor a 14 puntos se asoció a mortalidad en 87.5%, así como el puntaje menor a 14 se vinculó a supervivencia a 40 días en 83.33%. Conclusiones: La clasificación de Child-Pugh más lactato mayor de 14 puntos tiene una fuerte correlación con la mortalidad.
Abstract: Objective: This study aimed to establish if the Child-Pugh+lactate score is a reliable prognostic scoring tool as mortality predictor in cirrhotic patients admitted to the Médica Sur Clinic Foundation Intensive Care Unit. Material and methods: This was a 3-year, single-centered retrospective cohort study performed in a general ICU. Results: Twenty-eight cases were collected in the period from January 1, 2012 to December 31, 2014, of which a total of 16 patients (57.1%) died within the first 40 days after admission and 12 survived (42.9%). It was assessed if there was a correlation between death and a Child-Pugh lactate score greater than 14, finding an r = 0.708. Conclusions: A Child-Pugh+lactate score with a numerical value above 14 points has a direct relation with mortality in cirrhotic patients admitted to the ICU.
Resumo: Objetivo: Comprovar a capacidade prognóstica como preditor de mortalidade da Child Pugh lactato na população de pacientes cirróticos admitidos na terapia intensiva da Fundação Clínica Médica Sur. Material e métodos: Estudo de investigação clínica, coorte não concorrente, onde os dados foram coletados no período de 1 de Janeiro de 2012 a 31 Dezembro de 2014. Resultados: 28 casos admitidos na unidade de terapia intensiva da Fundação Clínica Médica Sur, diagnosticados com cirrose hepática, dos quais faleceram um total de 16 pacientes (57.1%) nos primeiros 40 dias após a admissão e sobreviveram 12 (42.9%). Calculou-se a existência de uma correlação entre a defunção e a Classificação Child Pugh lactato maior de 14 pontos, encontrando um r = 0.708. A pontuação CPL maior a 14 pontos está associado à mortalidade em 87.5% e inferior a 14 foi associado a sobrevida à 40 dias em um 83.33%. Conclusões: A Clasificação Child Pugh lactato maior a 14 pontos tem uma forte correlação com a mortalidade.
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INTRODUCTION: Mechanical ventilation is a therapy for vital support used in a significant proportion of critically ill patients. The right time to successfully discontinue this therapy is a challenge for the intensive care specialist. For this reason it is still a subject for research. The echocardiographic evaluation of the diastolic dysfunction, the diaphragm, and the lung have become an invaluable tool for weaning from mechanical ventilation protocols, especially in patients with difficult or prolonged weaning from mechanical ventilation. There is still a need to validate, in controlled trials, the efficacy of an ultrasound protocol for weaning from mechanical ventilation that integrates the three modalities in a single protocol. METHODS: Based on current literature, we developed a score justified by a mathematical model based on inequations. When χ â 5 the risk of failure in the weaning process rises, the weaning process should be suspended; when χ â 1 the risk of failure is low, the weaning process should be continued. CONCLUSIONS: The use of math models for decision-making is of great importance, as it sets an objective parameter within the existing evaluations. We proposed the use of inequations to set intervals of solution with the three points of care for ultrasound-guided weaning from mechanical ventilation. With this, the inequations proposed generate an area of certainty within the proposed values and the solution intervals.
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Modelos Teóricos , Respiração Artificial/métodos , Ultrassonografia/métodos , Desmame do Respirador/métodos , Estado Terminal , Tomada de Decisões , Ecocardiografia/métodos , Humanos , Fatores de TempoRESUMO
BACKGROUND: B-mode ultrasound can be used to measure diaphragm thickness at the zone of apposition. We believe it is necessary to develop normal values for diaphragm thickness at rest in a large group of healthy subjects and compare them with international results. METHODS: Ultrasound measurements of diaphragm thickness at expiratory rest were taken in 109 healthy individuals, with results stratified by sex, body mass index, and thorax circumference. The following methods were used for analysis and interpretation. Multivariable databases with descriptive statistical analyses were made. The Pearson chi-square test was used to evaluate the distribution between variables. Additionally, mean and SD values were calculated. For standardization, the data were separated by sex within a 95% CI, and we calculated a Z test. A 95% CI was also constructed for proportion analyses. RESULTS: One hundred nine healthy volunteers were included in the study, and the correlation between the body mass index and thorax circumference values with a Pearson chi-square test resulted in an r = 0.69. Additionally, the average value of diaphragmatic thickness was 0.19 ± 0.04 cm (95% CI 0.17-0.20 cm) for men and 0.14 ± 0.03 cm (95% CI 0.13-0.15 cm) for women (P = .001). There was no relation between body mass index thorax circumference, and diaphragmatic thickness. CONCLUSION: Real-time ultrasound of the diaphragm is a simple, inexpensive, and portable imaging technique that can provide qualitative anatomical information. The findings in this study show that sonographic diaphragm evaluations can be applied to the general population.
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Diafragma/anatomia & histologia , Diafragma/diagnóstico por imagem , Ultrassonografia/normas , Adulto , Índice de Massa Corporal , Distribuição de Qui-Quadrado , Expiração , Feminino , Voluntários Saudáveis , Humanos , Masculino , Análise Multivariada , Padrões de Referência , Valores de Referência , Descanso , Ultrassonografia/métodos , Adulto JovemRESUMO
Atypical haemolytic uraemic syndrome is one of the main variants of thrombotic microangiopathy, and is characterized by excessive complement activation in the microvasculature. It is also characterised by the clinical triad; non-immune haemolytic anaemia, thrombocytopenia, and acute renal failure. In addition, 60% of patients have mutations in the genes encoding complement regulators (factor H, factor I, membrane cofactor proteins, and thrombomodulin), activators (factor B and C3), as well as autoantibodies against factor H. Multiple factors are required for the disease to manifest itself, including a trigger and gene mutations with adequate penetration. Being one of the differential diagnoses of preeclampsia- eclampsia and HELLP syndrome means that the clinician must be familiar with the disease due to its high mortality, which can be modified with early diagnosis and comprehensive treatment.
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Síndrome Hemolítico-Urêmica Atípica , Complicações Hematológicas na Gravidez , Anticorpos Monoclonais Humanizados/uso terapêutico , Síndrome Hemolítico-Urêmica Atípica/diagnóstico , Síndrome Hemolítico-Urêmica Atípica/epidemiologia , Síndrome Hemolítico-Urêmica Atípica/fisiopatologia , Síndrome Hemolítico-Urêmica Atípica/terapia , Ativação do Complemento/genética , Diagnóstico Diferencial , Feminino , Predisposição Genética para Doença , Humanos , Mutação , Plasmaferese , Gravidez , Complicações Hematológicas na Gravidez/diagnóstico , Complicações Hematológicas na Gravidez/epidemiologia , Complicações Hematológicas na Gravidez/fisiopatologia , Complicações Hematológicas na Gravidez/terapia , Resultado da Gravidez , PrognósticoRESUMO
Resumen La sepsis es una de las principales causas de mortalidad en la unidad de terapia intensiva. El término especies reactivas de oxígeno (ERO) incluye moléculas con un electrón impar, llamadas radicales libres, como el anión superóxido, y también agentes oxidados como el peróxido de hidrógeno. Las ERO pueden reaccionar con muchas moléculas y pueden producir un daño no controlado; sin embargo, también tienen un papel fundamental en el metabolismo celular. El estrés oxidante es el resultado de la respuesta inflamatoria asociada a la sepsis que produce cambios en la función mitocondrial y en la microcirculación. El objetivo de este trabajo es revisar el papel de las ERO en sepsis y nuevos conceptos relacionados con la teoría metabólica del choque séptico.
Abstract Sepsis remains the most common cause of death in the intensive care unit. The term Reactive Oxygen Species (ROS) includes molecules with an unpaired electron, called free radicals, such as superoxide anion, and also oxidant agents such as hydrogen peroxide. ROS can react with several molecules and induce an uncontrolled damage in a variety of biomolecules. On the other hand, ROS have essential roles in cell function. Marked oxidative stress as a result of the inflammatory responses inherent with sepsis initiates changes in mitochondrial function and microcirculation. The aim of this paper is to review the roll of ROS in sepsis and new concepts related to the metabolic theory of septic shock.
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Obstetric hemorrhage is the leading cause of maternal mortality, responsible of 143,000 deaths every year. Thromboelastography is a tool that allows measuring the viscoelastic, dynamic and global properties of the blood, offering valuable information of coagulation alterations and help to guide early goal directed transfusional therapy. The purpose of this review is to evaluate the evidence of this tool in obstetric hemorrhage and the management of the associated coagulopathy.