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1.
Ugeskr Laeger ; 183(35)2021 08 30.
Artigo em Dinamarquês | MEDLINE | ID: mdl-34477089

RESUMO

The COVID-19-pandemic has had a huge impact on health and economics all over the world resulting in widespread vaccine development. Vaccine-induced immune thrombotic thrombocytropenia has been described, suggesting a link between the two adeno-vector vaccines ChAdOx1 nCoV-19 (Vaxzevria from AstraZeneca) and Ad26.COV2-S (Janssen from Johnson and Johnson). This rare clinical condition should be suspected in patients with headache, abdominal pain, suspected thrombosis or hemorrhage and thrombocytopenia within 3-30-day post vaccine. In this case report a previously healthy man had thrombocytopenia with fatal intracerebral haemorrhage which was suspected to be related to vaccine.


Assuntos
COVID-19 , Vacinas contra COVID-19 , Hemorragia Cerebral , Humanos , Masculino , SARS-CoV-2 , Vacinação
2.
Ugeskr Laeger ; 183(29)2021 07 19.
Artigo em Dinamarquês | MEDLINE | ID: mdl-34356021

RESUMO

Vaccine-induced immune thrombosis and thrombocytopenia (VITT) is a new syndrome, which has emerged after introduction of the adenovirus vector-based COVID-19 vaccines ChAdOx1 nCoV-19 og Ad26.COV2-SVITT is characterised by venous thrombosis at unusual, and often multiple localisations, especially including cerebral venous sinus thrombosis. Besides, bleeding manifestations often occur. Biochemically, VITT is characterised by thrombocytopaenia and elevated fibrin d-dimer. VITT is a rapidly progressing and potentially life-threatening syndrome where rapid diagnosis and treatment are essential as argued in this review.


Assuntos
COVID-19 , Trombocitopenia , Trombose , Vacinas , Vacinas contra COVID-19 , Humanos , SARS-CoV-2 , Trombocitopenia/induzido quimicamente , Trombocitopenia/terapia
3.
Blood Adv ; 5(12): 2569-2574, 2021 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-34137813

RESUMO

Recently, reports of severe thromboses, thrombocytopenia, and hemorrhage in persons vaccinated with the chimpanzee adenovirus-vectored vaccine (ChAdOx1 nCoV-19, AZD1222, Vaxzevria; Oxford/AstraZeneca) against severe acute respiratory syndrome coronavirus 2 have emerged. We describe an otherwise healthy 30-year-old woman who developed thrombocytopenia, ecchymosis, portal vein thrombosis, and cerebral venous sinus thrombosis the second week after she received the ChAdOx1 nCoV-19 vaccine. Extensive diagnostic workup for thrombosis predispositions showed heterozygosity for the prothrombin mutation, but no evidence of myeloproliferative neoplasia or infectious or autoimmune diseases. Her only temporary risk factor was long-term use of oral contraceptive pills (OCPs). Although both the prothrombin mutation and use of OCPs predispose to portal and cerebral vein thrombosis, the occurrence of multiple thromboses within a short time and the associated pattern of thrombocytopenia and consumption coagulopathy are highly unusual. A maximum 4T heparin-induced thrombocytopenia (HIT) score and a positive immunoassay for anti-platelet factor 4/heparin antibodies identified autoimmune HIT as a potential pathogenic mechanism. Although causality has not been established, our case emphasizes the importance of clinical awareness. Further studies of this potentially new clinical entity have suggested that it should be regarded as a vaccine-induced immune thrombotic thrombocytopenia.


Assuntos
COVID-19 , Trombocitopenia , Trombose , Adulto , Vacinas contra COVID-19 , Feminino , Humanos , SARS-CoV-2 , Trombocitopenia/induzido quimicamente , Trombose/etiologia , Vacinação
4.
Curr Opin Anaesthesiol ; 34(4): 537-543, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-34074885

RESUMO

PURPOSE OF REVIEW: Major trauma remains one of the leading causes of death worldwide with traumatic brain injury and uncontrolled traumatic bleeding as the main determinants of fatal outcome. Interestingly, the therapeutic approach to trauma-associated bleeding and coagulopathy shows differences between geographic regions, that are reflected in different guidelines and protocols. RECENT FINDINGS: This article summarizes main principles in coagulation diagnostics and compares different strategies for treatment of massive hemorrhage after trauma in different regions of the world. How would a bleeding trauma patient be managed if they got hit by the bus in the United States, United Kingdom, Germany, Switzerland, Austria, Denmark, Australia, or in Japan? SUMMARY: There are multiple coexistent treatment standards for trauma-induced coagulopathy in different countries and different trauma centers. Most of them initially follow a protocol-based approach and subsequently focus on predefined clinical and laboratory targets.


Assuntos
Transtornos da Coagulação Sanguínea , Ferimentos e Lesões , Austrália , Transtornos da Coagulação Sanguínea/etiologia , Transtornos da Coagulação Sanguínea/terapia , Alemanha , Objetivos , Hemorragia/etiologia , Hemorragia/terapia , Humanos , Japão , Reino Unido
5.
Ugeskr Laeger ; 183(24)2021 06 14.
Artigo em Dinamarquês | MEDLINE | ID: mdl-34120686

RESUMO

Neurological sequelae occur in more than 50% of children with arterial ischemic stroke. Early recognition and treatment are essential in improving outcome. However, diagnostic delay in paediatric stroke often extends beyond 24 hours, and children rarely access hyperacute recanalisation therapies. This review describes clinical presentations, risk factors and treatment of paediatric ischaemic stroke. Additionally, we share our experience from a systematic paediatric stroke pathway implemented in Eastern Denmark since 2017.


Assuntos
Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/terapia , Criança , Diagnóstico Tardio , Humanos , Fatores de Risco , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/etiologia
7.
Artigo em Inglês | MEDLINE | ID: mdl-33393084

RESUMO

BACKGROUND: Traumatic injury accounts for 800 000 deaths in the European Union annually. The main causes of deaths in trauma patients are exsanguination and multiple organ failure (MOF). We have studied >1000 trauma patients and identified shock-induced endotheliopathy (SHINE), the pathophysiological mechanism responsible for MOF and high mortality. Pilot studies indicate that low-dose iloprost (1 ng/kg/min) improves endothelial functionality in critically ill patients suggesting this intervention may improve patient outcome in traumatic SHINE. MATERIAL AND METHODS: This is a multicentre, randomized, blinded clinical investigator-initiated phase 2B trial in trauma patients with haemorrhagic shock-induced endotheliopathy. Patients are randomized 1:1 to 72 hours infusion of iloprost 1 ng/kg/min or Placebo (equal volume of saline). A total of 220 trauma patients will be included. The primary endpoint is the number of intensive care unit (ICU)-free days, within 28 days of admission. Secondary endpoints include 28- and 90-day all-cause mortality, hospital length of stay, vasopressor-free days in the intensive care unit (ICU) within 28 days, ventilator-free days in the ICU within 28 days, renal replacement-free days in the ICU within 28 days, number of serious adverse reactions and serious adverse events within the first 4 days of admission. DISCUSSION: This trial will test the safety and efficacy of administration of iloprost vs placebo for 72 hours in trauma patients with haemorrhagic shock-induced endotheliopathy. Trial endpoints focus on the potential effect of iloprost to reduce the need for ICU stay secondary to mitigation of organ failure. TRIAL REGISTRATION: SHINE-TRAUMA trial-EudraCT no. 2019-000936-24-Clinicaltrials.gov: NCT03903939 Ethics Committee no. H-19014482.

8.
Br J Neurosurg ; 35(3): 259-265, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32648493

RESUMO

BACKGROUND: Cerebral venous sinus thrombosis (CVST) is a rare cerebrovascular disorder. The majority of these patients respond favorably to systemic anticoagulation. However, a subset of patients will deteriorate clinically, despite optimal medical therapy. METHODS: Retrospective single center study of 28 consecutive CVST patients treated with systemic anticoagulation and additional endovascular therapy. RESULTS: Median age was 37.5 years (range 15-76 years), there were 21 (75%) women, and 20 (71%) had thrombosis involving ≥2 venous sinuses. Intracranial hemorrhage (ICH) was present at admission in 18 patients (64%). Endovascular therapy consisted of local thrombolysis in 26 (93%) patients; 9 patients (32%) had additional mechanical thrombectomy, and in 2 (7%) patients thrombectomy alone was performed. Complete recanalization at end of the final intervention was achieved in 15 patients (54%), partial recanalization in 11 patients (39%), whereas there was no recanalization in 2 patients (7%). On follow-up imaging, conducted between 3 and 6 months, recanalization further improved to 76%, 19% and 5%, respectively. A favorable outcome (mRS ≤ 2) was achieved in 63% of patients at 3 months, which improved to 79% at 6 months. Post-procedural ICH or volume expansion of preexisting ICH was seen in 9 patients (32%). In total 5 patients died (18%). CONCLUSIONS: Systemic anticoagulation with the addition of endovascular therapy with local thrombolysis and/or mechanical thrombectomy is a potential strategy to obtain recanalization in patients with CVST who deteriorate clinically despite medical therapy or are comatose. Endovascular therapy may increase the risk of ICH.


Assuntos
Procedimentos Endovasculares , Trombose dos Seios Intracranianos , Adolescente , Adulto , Idoso , Cavidades Cranianas , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Trombose dos Seios Intracranianos/diagnóstico por imagem , Trombose dos Seios Intracranianos/tratamento farmacológico , Trombectomia , Terapia Trombolítica , Resultado do Tratamento , Adulto Jovem
9.
Shock ; 55(3): 311-315, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-32826819

RESUMO

INTRODUCTION: Nearly half of severely injured patients suffer acute kidney injury (AKI), but little is known about its pathogenesis or optimal management. We hypothesized that endothelial dysfunction, evidenced by elevated systemic soluble thrombomodulin (sTM) and syndecan-1, would be associated with higher incidence, worsened severity, and prolonged duration of AKI after severe trauma. METHODS: A single-center cohort study of severely injured patients surviving ≥24 h from 2012 to 2016 was performed. Arrival plasma sTM and syndecan-1 were measured by ELISA. Outcomes included 7-day AKI incidence, stage, and prolonged AKI ≥2 days. The Kidney Disease Improving Global Outcomes guidelines were used for AKI diagnosis and staging. Univariate and multivariable analyses were performed. RESULTS: Of 477 patients, 78% were male. Patients had a median age of 38 (interquartile ranges [IQR] 27-54) and injury severity score of 17 (IQR 10-26). AKI developed in 51% of patients. Those with AKI were older and displayed worse arrival physiology. Patients with AKI had higher plasma levels of syndecan-1 (median 34.9 ng/mL vs. 20.1 ng/mL) and sTM (6.5 ng/mL vs. 4.8 ng/mL). After adjustment, sTM and syndecan-1 were both associated with higher AKI incidence, worse AKI severity, and prolonged AKI duration. The strength and precision of the association of sTM and these outcomes were greater than those for syndecan-1. A sensitivity analysis excluding patients with AKI on arrival demonstrated the same relationship. CONCLUSIONS: Elevated sTM and syndecan-1, indicating endothelial dysfunction, were associated with higher incidence, worsened severity, and prolonged duration of AKI after severe trauma. Treatments that stabilize the endothelium hold promise for AKI treatment in severely injured patients.

10.
Trials ; 21(1): 746, 2020 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-32847626

RESUMO

OBJECTIVES: To investigate the effect of continuous infusion of the potential endothelial cytoprotective agent prostacyclin (Iloprost) 1 ng/kg/min vs. placebo for 72 hours on pulmonary endotheliopathy in mechanically ventilated COVID-19 patients. TRIAL DESIGN: A multicenter, randomized (1:1, active: placebo), blinded, parallel group exploratory trial PARTICIPANTS: Inclusion criteria are: Adult patients (>18 years); Confirmed COVID-19 infection; Need for mechanical interventions; Endothelial biomarker soluble thrombomodulin >4ng/ml. EXCLUSION CRITERIA: Withdrawal from active therapy; Pregnancy (non-pregnancy confirmed by patient being postmenopausal (age 60 or above) or having a negative urine- or plasma-hCG); Known hypersensitivity to iloprost or to any of the other ingredients; Previously included in this trial or a prostacyclin trial within 30 days; Consent cannot be obtained; Life-threatening bleeding defined by the treating physician; Known severe heart failure (NYHA class IV); Suspected acute coronary syndrome The study is conducted at five intensive care units in the Capital Region of Denmark at Rigshospitalet, Herlev Hospital, Hvidovre Hospital, Bispebjerg Hospital, Nordsjællands Hospital. INTERVENTION AND COMPARATOR: The patients are randomized to 72-hours continuous infusion of either prostacyclin (Iloprost/Ilomedin) at a dose of 1 ng/kg/min or Placebo (normal saline). MAIN OUTCOMES: Primary endpoint: Days alive without mechanical ventilation in the intensive care units within 28 days RANDOMISATION: The randomisation sequence is performed in permuted blocks of variable sizes stratified for trial site using centralised, concealed allocation. The randomisation sequence is generated 1:1 (active/placebo) using the online randomisation software 'Sealed Envelope' ( https://www.sealedenvelope.com/ ). Once generated the randomisation sequence is formatted and uploaded into Research Electronic Data Capture system (REDCap) to facilitate centralised, web-based allocation according to local written instruction. BLINDING (MASKING): The following are blinded: all clinicians, patients, investigators, and those assessing the outcomes including the statisticians. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): Forty patients are planned to be randomized to each group, with a total sample size of 80 patients. TRIAL STATUS: Protocol version 1.4 dated May 25, 2020. Recruitment is ongoing. The recruitment was started June 15, 2020 and the anticipated finish of recruitment is February 28, 2021 with 90 days follow up hereafter. TRIAL REGISTRATION: Trial registration at clinicaltrialregisters.eu; EudraCT no. 2020-001296-33 on 3 April 2020 and at ClinicalTrials.gov Identifier: NCT04420741 on 9 June 2020 FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1).In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.


Assuntos
Infecções por Coronavirus/terapia , Iloprosta/uso terapêutico , Pneumonia Viral/terapia , Respiração Artificial , Vasodilatadores/uso terapêutico , Betacoronavirus , COVID-19 , Infecções por Coronavirus/sangue , Infecções por Coronavirus/tratamento farmacológico , Dinamarca , Endotélio Vascular/metabolismo , Endotélio Vascular/fisiopatologia , Humanos , Infusões Intravenosas , Unidades de Terapia Intensiva , Pandemias , Pneumonia Viral/sangue , SARS-CoV-2 , Trombomodulina/metabolismo
11.
JCI Insight ; 5(8)2020 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-32229722

RESUMO

BACKGROUNDPrehospital plasma improves survival in severely injured patients transported by air ambulance. We hypothesized that prehospital plasma would be associated with a reduction in immune imbalance and endothelial damage.METHODSWe sampled blood from 405 trauma patients enrolled in the Prehospital Air Medical Plasma (PAMPer) trial upon hospital admission (0 hours) and 24 hours post admission across 6 U.S. sites. We assayed samples for 21 inflammatory mediators and 7 markers associated with endothelial function and damage. We performed hierarchical clustering analysis (HCA) of these biomarkers of the immune response and endothelial injury. Regression analysis was used to control for differences across study and to assess any association with prehospital plasma resuscitation.RESULTSHCA distinguished two patient clusters with different injury patterns and outcomes. Patients in cluster A had greater injury severity and incidence of blunt trauma, traumatic brain injury, and mortality. Cluster A patients that received prehospital plasma showed improved 30-day survival. Prehospital plasma did not improve survival in cluster B patients. In an adjusted analysis of the most seriously injured patients, prehospital plasma was associated with an increase in adiponectin, IL-1ß, IL-17A, IL-23, and IL-17E upon admission, and a reduction in syndecan-1, TM, VEGF, IL-6, IP-10, MCP-1, and TNF-α, and an increase in IL-33, IL-21, IL-23, and IL-17E 24 hours later.CONCLUSIONPrehospital plasma may ameliorate immune dysfunction and the endotheliopathy of trauma. These effects of plasma may contribute to improved survival in injured patients.TRIAL REGISTRATIONNCT01818427.FUNDINGDepartment of Defense; National Institutes of Health, U.S. Army.


Assuntos
Biomarcadores/sangue , Serviços Médicos de Emergência/métodos , Inflamação/sangue , Plasma , Ferimentos e Lesões/terapia , Adulto , Resgate Aéreo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
12.
Acta Anaesthesiol Scand ; 64(5): 705-711, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31950481

RESUMO

BACKGROUND: In Europe 700.000 new cases of sepsis occur annually and more than 100.000 of these patients die due to multiorgan failure (MOF). We have identified shock-induced endotheliopathy (SHINE) to be associated with development of MOF and mortality. Furthermore, in patients with septic shock those with circulating levels of thrombomodulin (TM) above 10 ng/mL have twice the mortality (56% vs 28%) than those with levels below this level. Pilot studies indicate that infusion of iloprost (1 ng/kg/min) is associated with improved endothelial function in patients with septic shock. MATERIAL AND METHODS: This is a multicenter, randomized, blinded, investigator-initiated, adaptive phase 2B trial in up to 384 patients with septic shock-induced endotheliopathy defined by TM > 10 ng/mL who are allocated 1:1 to 72 hours continuous infusion of iloprost 1 ng/kg/min or placebo (equal volume of saline). The primary outcome is the mean daily modified Sequential Organ Failure Assessment (SOFA) score in the ICU up to day 90. Secondary outcomes include 28- and 90-day all-cause mortality, days alive without vasopressor in the ICU within 90 days, days alive without mechanical ventilation in the ICU within 90 days, days alive without renal replacement therapy in the ICU within 90 days, numbers of serious adverse reactions, and the number of serious adverse events within the first 7 days. DISCUSSION: This trial tests the safety and efficacy of iloprost vs placebo for 72 hours in patients with septic shock and SHINE. The outcome measures focus on the potential effect of the intervention to mitigate organ failure. TRIAL REGISTRATION: COMBAT-SHINE trial-EudraCT no. 2019-001131-31-Clinicaltrials.gov: NCT04123444-Ethics Committee no. H-19018258.


Assuntos
Endotélio Vascular/patologia , Iloprosta/uso terapêutico , Insuficiência de Múltiplos Órgãos/etiologia , Insuficiência de Múltiplos Órgãos/prevenção & controle , Choque Séptico/complicações , Vasodilatadores/uso terapêutico , Dinamarca , Endotélio Vascular/efeitos dos fármacos , Humanos , Iloprosta/efeitos adversos , Escores de Disfunção Orgânica , Projetos de Pesquisa , Resultado do Tratamento , Vasodilatadores/efeitos adversos
13.
Ann Surg ; 272(6): 1140-1148, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-31274658

RESUMO

OBJECTIVE: Investigate the endothelial cell phenotype (s) that causes Shock-Induced Endotheliopathy in trauma. BACKGROUND: We have studied more than 2750 trauma patients and identified that patients with high circulating syndecan-1 (endothelial glycocalyx damage marker) in plasma have an increased mortality rate compared with patients with lower levels. Notably, we found that patients suffering from the same trauma severity could develop significantly different degrees of endothelial dysfunction as measured by syndecan-1. METHODS: Prospective observational study of 20 trauma patients admitted to a Level 1 Trauma Centre and 20 healthy controls. Admission plasma syndecan-1 level and mass spectrometry were measured and analyzed by computational network analysis of our genome-scale metabolic model of the microvascular endothelial cell function. RESULTS: Trauma patients had a significantly different endothelial metabolic profile compared with controls. Among the patients, 4 phenotypes were identified. Three phenotypes were independent of syndecan-1 levels. We developed genome-scale metabolic models representative of the observed phenotypes. Within these phenotypes, we observed differences in the cell fluxes from glucose and palmitate to produce Acetyl-CoA, and secretion of heparan sulfate proteoglycan (component of syndecan-1). CONCLUSIONS: We confirm that trauma patients have a significantly different metabolic profile compared with controls. A minimum of 4 shock-induced endotheliopathy phenotypes were identified, which were independent of syndecan-1level (except 1 phenotype) verifying that the endothelial response to trauma is heterogeneous and most likely driven by a genetic component. Moreover, we introduced a new research tool in trauma by using metabolic systems biology, laying the foundation for personalized medicine.


Assuntos
Endotélio Vascular , Choque/complicações , Choque/metabolismo , Sindecana-1/sangue , Doenças Vasculares/etiologia , Doenças Vasculares/metabolismo , Ferimentos e Lesões/complicações , Adulto , Pesquisa Biomédica , Células Endoteliais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Estudos Prospectivos , Choque/sangue , Doenças Vasculares/sangue , Ferimentos e Lesões/sangue
14.
Burns ; 46(2): 386-393, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31866179

RESUMO

Shedding of syndecan-1 from the endothelial glycocalyx layer (EGL), referred to as endotheliopathy of trauma (EoT), is associated with poorer outcomes. This study aims to determine if EoT is also present in the burn population. We enrolled 458 burn and non-burn trauma patients at a Level 1 trauma center and defined EoT by a syndecan-1 level of ≥40 ng/mL. Sixty-eight of the enrolled patients had burns with a median TBSA of 19%, with 27.9% also suffering inhalational injury (II). Mortality was similar between the burn and non-burn group, also for patients with EoT. The incidence of II was significantly greater in the EoT+ burn group compared to the EoT- group (p = 0.038). Patients with II received significantly larger amounts of i.v. fluids (p = 0.001). The incidence of EoT was significantly different between the II-groups, as was mortality (pEoT = 0.038, pmortality < 0.001). EoT is attributed to the shock rather than the mechanism of trauma and may in burns be associated to II rather than TBSA. Patients with burns and II had worse outcomes and higher mortality compared to patients with burns alone. Burn injury induces EGL shedding similar to that in non-burn patients with EoT, and results in similar higher rate of mortality.


Assuntos
Queimaduras/metabolismo , Células Endoteliais/metabolismo , Endotélio Vascular/metabolismo , Hidratação/estatística & dados numéricos , Glicocálix/metabolismo , Choque Traumático/metabolismo , Sindecana-1/metabolismo , Trombomodulina/metabolismo , Adulto , Queimaduras/fisiopatologia , Queimaduras/terapia , Endotélio Vascular/fisiopatologia , Feminino , Humanos , Escala de Gravidade do Ferimento , Unidades de Terapia Intensiva , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Mortalidade , Ressuscitação , Choque Traumático/fisiopatologia , Choque Traumático/terapia , Lesão por Inalação de Fumaça , Ferimentos e Lesões/metabolismo , Ferimentos e Lesões/fisiopatologia , Ferimentos e Lesões/terapia
15.
Ann Surg ; 269(6): 1184-1191, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31082919

RESUMO

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


Assuntos
Anexina A2/sangue , Fibrinólise/fisiologia , Proteínas S100/sangue , Ferimentos e Lesões/sangue , Ferimentos e Lesões/complicações , Adulto , Idoso , Fatores de Coagulação Sanguínea/metabolismo , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Taxa de Sobrevida , Tromboelastografia , Ferimentos e Lesões/mortalidade , Adulto Jovem
16.
Blood Transfus ; 17(2): 112-136, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30865585

RESUMO

Patient blood management (PBM) is the timely application of evidence-informed medical and surgical concepts designed to maintain haemoglobin concentration, optimise haemostasis, and minimise blood loss in an effort to improve patient outcomes. The aim of this consensus statement is to provide recommendations on the prevention and treatment of postpartum haemorrhage as part of PBM in obstetrics. A multidisciplinary panel of physicians with expertise in obstetrics, anaesthesia, haematology, and transfusion medicine was convened by the Network for the Advancement of Patient Blood Management, Haemostasis and Thrombosis (NATA) in collaboration with the International Federation of Gynaecology and Obstetrics (FIGO), the European Board and College of Obstetrics and Gynaecology (EBCOG), and the European Society of Anaesthesiology (ESA). Members of the task force assessed the quantity, quality and consistency of the published evidence, and formulated recommendations using the system developed by the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) working group. The recommendations in this consensus statement are intended for use by clinical practitioners managing perinatal care of women in all settings, and by policy-makers in charge of decision making for the update of clinical practice in health care establishments.


Assuntos
Hemorragia Pós-Parto/prevenção & controle , Hemorragia Pós-Parto/terapia , Anemia/prevenção & controle , Transfusão de Sangue/métodos , Gerenciamento Clínico , Feminino , Hemostasia , Humanos , Hemorragia Pós-Parto/sangue , Hemorragia Pós-Parto/etiologia , Gravidez , Fatores de Risco , Sociedades Médicas
17.
J Thromb Haemost ; 17(3): 441-448, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30609290

RESUMO

Essentials The response of thromboelastometry (ROTEM) parameters to therapy is unknown. We prospectively recruited hemorrhaging trauma patients in six level-1 trauma centres in Europe. Blood products and pro-coagulants prevent further derangement of ROTEM results. ROTEM algorithms can be used to treat and monitor trauma induced coagulopathy. SUMMARY: Background Rotational thromboelastometry (ROTEM) can detect trauma-induced coagulopathy (TIC) and is used in transfusion algorithms. The response of ROTEM to transfusion therapy is unknown. Objectives To determine the response of ROTEM profiles to therapy in bleeding trauma patients. Patients/Methods A prospective multicenter study in bleeding trauma patients (receiving ≥ 4 red blood cell [RBC] units) was performed. Blood was drawn in the emergency department, after administration of 4, 8 and 12 RBC units and 24 h post-injury. The response of ROTEM to plasma, platelets (PLTs), tranexamic acid (TXA) and fibrinogen products was evaluated in the whole cohort as well as in the subgroup of patients with ROTEM values indicative of TIC. Results Three hundred and nine bleeding and shocked patients were included. A mean dose of 3.8 g of fibrinogen increased FIBTEM CA5 by 5.2 mm (IQR: 4.1-6.3 mm). TXA administration decreased lysis by 5.4% (4.3-6.5%). PLT transfusion prevented further derangement of parameters of clot formation. The effect of PLTs on EXTEM ca5 values was more pronounced in patients with a ROTEM value indicative of TIC than in the whole cohort. Plasma transfusion decreased EXTEM clotting time by 3.1 s (- 10 s to 3.9 s) in the whole cohort and by 10.6 s (- 45 s to 24 s) in the subgroup of patients with a ROTEM value indicative of TIC. Conclusion The effects of therapy on ROTEM values were small, but prevented further derangement of test results. In patients with ROTEM values indicative of TIC, the efficacy of PLTs and plasma in correcting deranged ROTEM parameters is possibly more robust.


Assuntos
Técnicas de Apoio para a Decisão , Hemorragia/terapia , Hemostasia , Assistência Centrada no Paciente , Ressuscitação/métodos , Tromboelastografia , Ferimentos e Lesões/terapia , Adulto , Antifibrinolíticos/administração & dosagem , Antifibrinolíticos/efeitos adversos , Tomada de Decisão Clínica , Transfusão de Eritrócitos/efeitos adversos , Europa (Continente) , Feminino , Fibrinogênio/administração & dosagem , Fibrinogênio/efeitos adversos , Hemorragia/sangue , Hemorragia/diagnóstico , Hemostasia/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Seleção de Pacientes , Transfusão de Plaquetas/efeitos adversos , Valor Preditivo dos Testes , Estudos Prospectivos , Ressuscitação/efeitos adversos , Fatores de Tempo , Ácido Tranexâmico/administração & dosagem , Ácido Tranexâmico/efeitos adversos , Resultado do Tratamento , Ferimentos e Lesões/sangue , Ferimentos e Lesões/diagnóstico
18.
Burns ; 45(4): 755-762, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30292526

RESUMO

Major burn surgery is often associated with excessive bleeding and massive transfusion, and the development of a coagulopathy during major burn surgery is associated with increased morbidity and mortality. The aim of this study was to review the literature on intraoperative haemostatic resuscitation of burn patients during necrectomy to reveal strategies applied for haemostatic monitoring and resuscitation. We searched PubMed, EMBASE, and CENTRAL for studies published in the period 2006-2017 concerning bleeding issues related to burn surgery i.e. coagulopathy, transfusion requirements and clinical outcomes. In a broad search, a total of 1375 papers were identified. 124 of these fulfilled the inclusion criteria, and six of these were included for review. The literature confirmed that transfusion requirements increases with burn injury severity and that haemostatic monitoring by TEG® (thrombelastography) or ROTEM® (rotational thromboelastometry) significantly decreased intraoperative transfusions and was useful in predicting and goal-directing haemostatic therapy during excision surgery. Resuscitation of bleeding during major burn surgery in many instances was neither standardized nor haemostatic. We suggest that resuscitation should aim for normal haemostasis during the bleeding phase through close haemostatic monitoring and resuscitation. Randomised controlled trials are highly warranted to confirm the benefit of this concept.


Assuntos
Transtornos da Coagulação Sanguínea/terapia , Perda Sanguínea Cirúrgica , Queimaduras/cirurgia , Hemorragia/terapia , Transtornos da Coagulação Sanguínea/sangue , Transtornos da Coagulação Sanguínea/diagnóstico , Transfusão de Sangue/métodos , Hemorragia/sangue , Técnicas Hemostáticas , Humanos , Testes Imediatos , Ressuscitação/métodos , Tromboelastografia/métodos
19.
Shock ; 51(2): 180-184, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-29621120

RESUMO

INTRODUCTION: Severe trauma is accompanied by endothelial glycocalyx disruption, which drives coagulopathy, increasing transfusion requirements and death. This syndrome has been termed endotheliopathy of trauma (EOT). Some have suggested EOT results from endothelial cellular damage and apoptosis. Endothelial microvesicles (EMVs) represent cellular damage. We hypothesized that EOT is associated with endothelial damage and apoptosis resulting in an increase in circulating EMVs. METHODS: Prospective, observational study enrolling severely injured patients. Twelve patients with EOT, based on elevated Syndecan-1 levels, were matched with 12 patients with lower levels, based on Injury Severity Score (ISS), abbreviated injury scale profile, and age. Thrombelastography and plasma levels of biomarkers indicative of cellular damage were measured from blood samples collected on admission. EMVs were determined by flow cytometry using varied monoclonal antibodies associated with endothelial cells. Significance was set at P < 0.05. RESULTS: Admission physiology and ISS (29 vs. 28) were similar between groups. Patients with EOT had higher Syndecan-1, 230 (158, 293) vs. 19 (14, 25) ng/mL, epinephrine, and soluble thrombomodulin levels. Based on thrombelastography, EOT had reductions in clot initiation, amplification, propagation and strength, and a greater frequency of transfusion, 92% vs. 33%. There were no differences in EMVs irrespective of the antibody used. Plasma norepinephrine, sE-selectin, sVE-cadherin, and histone-complexed DNA fragments levels were similar. CONCLUSION: In trauma patients presenting with EOT, endothelial cellular damage or apoptosis does not seem to occur based on the absence of an increase in EMVs and other biomarkers. Thus, this suggests endothelial glycocalyx disruption is the underlying primary cause of EOT.


Assuntos
Apoptose , Transtornos da Coagulação Sanguínea , Células Endoteliais , Glicocálix , Ferimentos e Lesões , Adulto , Biomarcadores/sangue , Transtornos da Coagulação Sanguínea/sangue , Transtornos da Coagulação Sanguínea/etiologia , Transtornos da Coagulação Sanguínea/patologia , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Feminino , Glicocálix/metabolismo , Glicocálix/patologia , Humanos , Escala de Gravidade do Ferimento , Masculino , Pessoa de Meia-Idade , Ferimentos e Lesões/sangue , Ferimentos e Lesões/complicações , Ferimentos e Lesões/patologia
20.
Ann Surg ; 270(6): 1178-1185, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-29794847

RESUMO

OBJECTIVE: Developing pragmatic data-driven algorithms for management of trauma induced coagulopathy (TIC) during trauma hemorrhage for viscoelastic hemostatic assays (VHAs). BACKGROUND: Admission data from conventional coagulation tests (CCT), rotational thrombelastometry (ROTEM) and thrombelastography (TEG) were collected prospectively at 6 European trauma centers during 2008 to 2013. METHODS: To identify significant VHA parameters capable of detecting TIC (defined as INR > 1.2), hypofibrinogenemia (< 2.0 g/L), and thrombocytopenia (< 100 x10/L), univariate regression models were constructed. Area under the curve (AUC) was calculated, and threshold values for TEG and ROTEM parameters with 70% sensitivity were included in the algorithms. RESULTS: A total of, 2287 adult trauma patients (ROTEM: 2019 and TEG: 968) were enrolled. FIBTEM clot amplitude at 5 minutes (CA5) had the largest AUC and 10 mm detected hypofibrinogenemia with 70% sensitivity. The corresponding value for functional fibrinogen (FF) TEG maximum amplitude (MA) was 19 mm. Thrombocytopenia was similarly detected using the calculated threshold EXTEM-FIBTEM CA5 30 mm. The corresponding rTEG-FF TEG MA was 46 mm. TIC was identified by EXTEM CA5 41 mm, rTEG MA 64 mm (80% sensitivity). For hyperfibrinolysis, we examined the relationship between viscoelastic lysis parameters and clinical outcomes, with resulting threshold values of 85% for EXTEM Li30 and 10% for rTEG Ly30.Based on these analyses, we constructed algorithms for ROTEM, TEG, and CCTs to be used in addition to ratio driven transfusion and tranexamic acid. CONCLUSIONS: We describe a systematic approach to define threshold parameters for ROTEM and TEG. These parameters were incorporated into algorithms to support data-driven adjustments of resuscitation with therapeutics, to optimize damage control resuscitation practice in trauma.


Assuntos
Algoritmos , Transtornos da Coagulação Sanguínea/diagnóstico , Transtornos da Coagulação Sanguínea/terapia , Hemorragia/terapia , Ferimentos e Lesões/complicações , Adulto , Transtornos da Coagulação Sanguínea/etiologia , Testes de Coagulação Sanguínea , Feminino , Hemorragia/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Sensibilidade e Especificidade , Tromboelastografia , Ferimentos e Lesões/terapia
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