RESUMO
AIM: This population-based study investigated the occurrence of capillary leak syndrome (CLS) in children with multisystem inflammatory syndrome in children (MIS-C), associated with COVID-19. We also examined associations between CLS and MIS-C disease severity. METHODS: All eligible individuals aged 0-18 years, who were diagnosed with MIS-C in Skåne, southern Sweden, from 1 April 2020 to 31 July 2021, were studied. They were all included in the Pediatric Rheumatology Quality Register and clinical and laboratory data were compared between patients with and without CLS. RESULTS: We included 31 patients (61% male) with MIS-C in the study. The median age at diagnosis was 10.6 years (range 1.99-17.15) and 45% developed CLS. All six patients who required intensive care had CLS. Patients with CLS also had a higher incidence of reduced cardiac function, measured as low ejection fraction. The CLS group exhibited significantly higher C-reactive protein values (p < 0.001) and N-terminal pro-B-type natriuretic peptide levels (p < 0.001), as well as lower platelet counts (p = 0.03), during the first week of treatment. Individuals with CLS also received more intense immunosuppression. CONCLUSION: CLS was a common complication of MIS-C in our study and these patients had a more severe disease course that required more intensive treatment.
Assuntos
COVID-19 , Síndrome de Vazamento Capilar , Índice de Gravidade de Doença , Síndrome de Resposta Inflamatória Sistêmica , Humanos , COVID-19/complicações , COVID-19/epidemiologia , Criança , Masculino , Síndrome de Resposta Inflamatória Sistêmica/epidemiologia , Síndrome de Resposta Inflamatória Sistêmica/diagnóstico , Síndrome de Vazamento Capilar/epidemiologia , Síndrome de Vazamento Capilar/etiologia , Síndrome de Vazamento Capilar/diagnóstico , Feminino , Adolescente , Pré-Escolar , Lactente , Suécia/epidemiologiaRESUMO
SARS-CoV-2 vaccine ChAdOx1 nCoV-19 (AstraZeneca) causes a thromboembolic complication termed vaccine-induced immune thrombotic thrombocytopenia (VITT). Using biophysical techniques, mouse models, and analysis of VITT patient samples, we identified determinants of this vaccine-induced adverse reaction. Super-resolution microscopy visualized vaccine components forming antigenic complexes with platelet factor 4 (PF4) on platelet surfaces to which anti-PF4 antibodies obtained from VITT patients bound. PF4/vaccine complex formation was charge-driven and increased by addition of DNA. Proteomics identified substantial amounts of virus production-derived T-REx HEK293 proteins in the ethylenediaminetetraacetic acid (EDTA)-containing vaccine. Injected vaccine increased vascular leakage in mice, leading to systemic dissemination of vaccine components known to stimulate immune responses. Together, PF4/vaccine complex formation and the vaccine-stimulated proinflammatory milieu trigger a pronounced B-cell response that results in the formation of high-avidity anti-PF4 antibodies in VITT patients. The resulting high-titer anti-PF4 antibodies potently activated platelets in the presence of PF4 or DNA and polyphosphate polyanions. Anti-PF4 VITT patient antibodies also stimulated neutrophils to release neutrophil extracellular traps (NETs) in a platelet PF4-dependent manner. Biomarkers of procoagulant NETs were elevated in VITT patient serum, and NETs were visualized in abundance by immunohistochemistry in cerebral vein thrombi obtained from VITT patients. Together, vaccine-induced PF4/adenovirus aggregates and proinflammatory reactions stimulate pathologic anti-PF4 antibody production that drives thrombosis in VITT. The data support a 2-step mechanism underlying VITT that resembles the pathogenesis of (autoimmune) heparin-induced thrombocytopenia.
Assuntos
Complexo Antígeno-Anticorpo/imunologia , Autoanticorpos/imunologia , COVID-19/prevenção & controle , Proteínas do Capsídeo/efeitos adversos , ChAdOx1 nCoV-19/efeitos adversos , Contaminação de Medicamentos , Vetores Genéticos/efeitos adversos , Células HEK293/imunologia , Imunoglobulina G/imunologia , Fator Plaquetário 4/imunologia , Púrpura Trombocitopênica Idiopática/etiologia , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus/efeitos adversos , Adenoviridae/imunologia , Animais , Complexo Antígeno-Anticorpo/ultraestrutura , Autoanticorpos/biossíntese , Síndrome de Vazamento Capilar/etiologia , Proteínas do Capsídeo/imunologia , Linhagem Celular Transformada , ChAdOx1 nCoV-19/química , ChAdOx1 nCoV-19/imunologia , ChAdOx1 nCoV-19/toxicidade , Difusão Dinâmica da Luz , Epitopos/química , Epitopos/imunologia , Armadilhas Extracelulares/imunologia , Extravasamento de Materiais Terapêuticos e Diagnósticos/etiologia , Vetores Genéticos/imunologia , Células HEK293/química , Humanos , Imageamento Tridimensional , Imunoglobulina G/biossíntese , Inflamação , Camundongos , Microscopia/métodos , Ativação Plaquetária , Proteômica , Púrpura Trombocitopênica Idiopática/sangue , Púrpura Trombocitopênica Idiopática/imunologia , Trombose dos Seios Intracranianos/diagnóstico por imagem , Trombose dos Seios Intracranianos/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Cultura de VírusRESUMO
Traumatic brain injury-induced coagulopathy (TBI-IC) causes life-threatening secondary intracranial bleeding. Its pathogenesis differs mechanistically from that of coagulopathy arising from extracranial injuries and hemorrhagic shock, but it remains poorly understood. We report results of a study designed to test the hypothesis that von Willebrand factor (VWF) released during acute TBI is intrinsically hyperadhesive because its platelet-binding A1-domain is exposed and contributes to TBI-induced vascular leakage and consumptive coagulopathy. This hyperadhesive VWF can be selectively blocked by a VWF A2-domain protein to prevent TBI-IC and to improve neurological function with a minimal risk of bleeding. We demonstrated that A2 given through intraperitoneal injection or IV infusion reduced TBI-induced death by >50% and significantly improved the neurological function of C57BL/6J male mice subjected to severe lateral fluid percussion injury. A2 protected the endothelium from extracellular vesicle-induced injury, reducing TBI-induced platelet activation and microvesiculation, and preventing a TBI-induced hypercoagulable state. A2 achieved this therapeutic efficacy by specifically blocking the A1 domain exposed on the hyperadhesive VWF released during acute TBI. These results suggest that VWF plays a causal role in the development of TBI-IC and is a therapeutic target for this life-threatening complication of TBI.
Assuntos
Lesões Encefálicas Traumáticas/tratamento farmacológico , Fragmentos de Peptídeos/farmacologia , Fator de von Willebrand/antagonistas & inibidores , Reação de Fase Aguda , Animais , Plaquetas/metabolismo , Lesões Encefálicas Traumáticas/complicações , Síndrome de Vazamento Capilar/etiologia , Síndrome de Vazamento Capilar/prevenção & controle , Estudos de Casos e Controles , Hemorragia Cerebral/etiologia , Hemorragia Cerebral/prevenção & controle , Circulação Cerebrovascular , Coagulação Intravascular Disseminada/etiologia , Coagulação Intravascular Disseminada/prevenção & controle , Endotélio Vascular/efeitos dos fármacos , Vesículas Extracelulares , Humanos , Infusões Intravenosas , Injeções Intraperitoneais , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fragmentos de Peptídeos/administração & dosagem , Fragmentos de Peptídeos/uso terapêutico , Ativação Plaquetária/efeitos dos fármacos , Conformação Proteica , Domínios Proteicos/efeitos dos fármacos , Proteínas Recombinantes de Fusão/administração & dosagem , Proteínas Recombinantes de Fusão/farmacologia , Proteínas Recombinantes de Fusão/uso terapêutico , Fator de von Willebrand/química , Fator de von Willebrand/fisiologia , Fator de von Willebrand/uso terapêuticoRESUMO
Brucellosis can lead to pathological changes of multiple systems. Capillary leak syndrome (CLS) is a clinical syndrome caused by different reasons, mainly characterized by hypotension, hypoproteinemia and systemic edema. The condition is critical and the clinical manifestations are complex, and multiple organ dysfunction syndrome (MODS) may occur in severe cases. CLS caused by brucellosis is extremely rare. The diagnosis and treatment of a patient with brucellosis complicated with CLS and MODS was analyzed in this paper, in order to improve the knowledge of clinicians about brucellosis and its complications.
Assuntos
Brucelose , Síndrome de Vazamento Capilar , Humanos , Síndrome de Vazamento Capilar/diagnóstico , Síndrome de Vazamento Capilar/etiologia , Síndrome de Vazamento Capilar/terapia , Insuficiência de Múltiplos Órgãos/etiologia , Brucelose/complicaçõesRESUMO
We report 2 fatal exacerbations of systemic capillary leak syndrome (SCLS), also known as Clarkson disease, associated with coronavirus disease (COVID-19) in the United States. One patient carried an established diagnosis of SCLS and the other sought treatment for new-onset hypotensive shock, hemoconcentration, and anasarca, classic symptoms indicative of an SCLS flare. Both patients had only mild-to-moderate symptoms of COVID-19. This clinical picture suggests that these patients succumbed to complications of SCLS induced by infection with severe acute respiratory syndrome coronavirus 2. Persons with known or suspected SCLS may be at increased risk for developing a disease flare in the setting of mild-to-moderate COVID-19 infection.
Assuntos
COVID-19 , Síndrome de Vazamento Capilar , Síndrome de Vazamento Capilar/diagnóstico , Síndrome de Vazamento Capilar/etiologia , Humanos , SARS-CoV-2 , Estados UnidosRESUMO
BACKGROUND: Since the first observations of patients with COVID-19, significant hypoalbuminaemia was detected. Its causes have not been investigated yet. OBJECTIVE: We hypothesized that pulmonary capillary leakage affects the severity of respiratory failure, causing a shift of fluids and proteins through the epithelial-endothelial barrier. METHODS: One hundred seventy-four COVID-19 patients with respiratory symptoms, 92 admitted to the intermediate medicine ward (IMW) and 82 to the intensive care unit (ICU) at Luigi Sacco Hospital in Milan, were studied. RESULTS: Baseline characteristics at admission were considered. Proteins, interleukin 8 (IL-8) and interleukin 10 (IL-10) in bronchoalveolar lavage fluid (BALF) were analysed in 26 ICU patients. In addition, ten autopsy ultrastructural lung studies were performed in patients with COVID-19 and compared with postmortem findings in a control group (bacterial pneumonia-ARDS and H1N1-ARDS). ICU patients had lower serum albumin than IMW patients [20 (18-23) vs 28 (24-33) g L-1 , P < 0.001]. Serum albumin was lower in more compromised groups (lower PaO2 -to-FiO2 ratio and worst chest X-ray findings) and was associated with 30 days of probability of survival. Protein concentration was correlated with IL-8 and IL-10 levels in BALF. Electron microscopy examinations of eight out of ten COVID-19 lung tissues showed loosening of junctional complexes, quantitatively more pronounced than in controls, and direct viral infection of type 2 pneumocytes and endothelial cells. CONCLUSION: Hypoalbuminaemia may serve as severity marker of epithelial-endothelial damage in patients with COVID-19. There are clues that pulmonary capillary leak syndrome plays a key role in the pathogenesis of COVID-19 and might be a potential therapeutic target.
Assuntos
COVID-19/complicações , Hipoalbuminemia/etiologia , Idoso , Líquido da Lavagem Broncoalveolar/química , COVID-19/sangue , Síndrome de Vazamento Capilar/etiologia , Endotélio Vascular/patologia , Feminino , Humanos , Interleucina-10/análise , Interleucina-8/análise , Pulmão/diagnóstico por imagem , Pulmão/patologia , Masculino , Pessoa de Meia-Idade , Mucosa Respiratória/patologia , Estudos Retrospectivos , UltrassonografiaRESUMO
BACKGROUND: Capillary leakage is a key contributor to the pathological host response to infections. The underlying mechanisms remain incompletely understood, and the role of microRNAs (MIR) has not been investigated in detail. We hypothesized that specific MIRs might be regulated directly in the endothelium thereby contributing to vascular leakage. METHODS: SmallRNA sequencing of endotoxemic murine pulmonary endothelial cells (ECs) was done to detect regulated vascular MIRs. In vivo models: transgenic zebrafish (flk1:mCherry/l-fabp:eGFP-DPB), knockout/wildtype mouse (B6.Cg-Mir155tm1.1Rsky/J); disease models: LPS 17.5 mg/kgBW and cecal ligation and puncture (CLP); in vitro models: stimulated human umbilical vein EC (HUVECs), transendothelial electrical resistance. RESULTS: Endothelial MIR155 was identified as a promising candidate in endotoxemic murine pulmonary ECs (25 × upregulation). Experimental overexpression in a transgenic zebrafish line and in HUVECs was sufficient to induce spontaneous vascular leakage. To the contrary, genetic MIR155 reduction protects against permeability both in vitro and in endotoxemia in vivo in MIR155 heterozygote knockout mice thereby improving survival by 40%. A tight junction protein, Claudin-1, was down-regulated both in endotoxemia and by experimental MIR155 overexpression. Translationally, MIR155 was detectable at high levels in bronchoalveolar fluid of patients with ARDS compared to healthy human subjects. CONCLUSIONS: We found that MIR155 is upregulated in the endothelium in mouse and men as part of a systemic inflammatory response and might contribute to the pathophysiology of vascular leakage in a Claudin-1-dependent manner. Future studies have to clarify whether MIR155 could be a potential therapeutic target.
Assuntos
Síndrome de Vazamento Capilar/tratamento farmacológico , Endotélio Vascular/efeitos dos fármacos , MicroRNAs/farmacologia , Animais , Síndrome de Vazamento Capilar/etiologia , Endotélio Vascular/metabolismo , Humanos , Camundongos , MicroRNAs/uso terapêutico , Síndrome de Resposta Inflamatória Sistêmica/complicações , Síndrome de Resposta Inflamatória Sistêmica/tratamento farmacológico , Peixe-ZebraRESUMO
Activated mast cells trigger edema in allergic and inflammatory disease. We report a paracrine mechanism by which mast cell-released heparin increases vascular permeability in vivo. Heparin activated the protease factor XII, which initiates bradykinin formation in plasma. Targeting factor XII or kinin B2 receptors abolished heparin-triggered leukocyte-endothelium adhesion and interfered with a mast cell-driven drop in blood pressure in rodents. Intravital laser scanning microscopy and tracer measurements showed heparin-driven fluid extravasation in mouse skin microvessels. Ablation of factor XII or kinin B2 receptors abolished heparin-induced skin edema and protected mice from allergen-activated mast cell-driven leakage. In contrast, heparin and activated mast cells induced excessive edema in mice deficient in the major inhibitor of factor XII, C1 esterase inhibitor. Allergen exposure triggered edema attacks in hereditary angioedema patients, lacking C1 esterase inhibitor. The data indicate that heparin-initiated bradykinin formation plays a fundamental role in mast cell-mediated diseases.
Assuntos
Bradicinina/biossíntese , Síndrome de Vazamento Capilar/fisiopatologia , Permeabilidade Capilar/fisiologia , Heparina/fisiologia , Mastócitos/metabolismo , Anafilaxia Cutânea Passiva/fisiologia , Animais , Bradicinina/genética , Síndrome de Vazamento Capilar/etiologia , Adesão Celular , Proteína Inibidora do Complemento C1/fisiologia , Edema/etiologia , Edema/fisiopatologia , Células Endoteliais/patologia , Ativação Enzimática , Fator XII/fisiologia , Heparina/metabolismo , Hipotensão/etiologia , Hipotensão/fisiopatologia , Imunoglobulina E/imunologia , Sistema Calicreína-Cinina/fisiologia , Leucócitos/fisiologia , Masculino , Camundongos , Comunicação Parácrina/fisiologia , Plasma , Ratos , Transdução de Sinais/fisiologia , Pele/irrigação sanguíneaRESUMO
BACKGROUND: Burn injury is associated with a long-standing inflammatory reaction. The use of albumin solutions for plasma volume support is controversial because of concerns of increased capillary leakage, which could aggravate the commonly seen interstitial oedema. METHODS: In the present open controlled clinical trial, an intravenous infusion of 20% albumin at 3 mL/kg was given over 30 min to 15 burn patients and 15 healthy volunteers. Blood samples and urine were collected for 5 h. Plasma dilution, plasma albumin and colloid osmotic pressure were compared. Mass balance calculations were used to estimate plasma volume expansion and capillary leakage of fluid and albumin. RESULTS: The patients were studied between 4 and 14 (median, 7) days after the burn injury, which spread over 7-48% (median, 15%) of the total body surface area. The albumin solution expanded the plasma volume by almost 15%, equivalent to twice the infused volume, in both groups. The urinary excretion exceeded the infused volume by a factor of 2.5. Capillary leakage of albumin occurred at a rate of 3.4 ± 1.5 g/h in burn patients and 3.7 ± 1.6 g/h in the volunteers (P = 0.61), which corresponded to 2.4 ± 1.0% and 2.5 ± 1.2% per hour of the intravascular pool (P = 0.85). The median half-life of the plasma volume expansion was 5.9 (25th-75th percentiles 2.7-11.7) h in the burn patients and 6.9 (3.4-8.5) h in the volunteers (P = 0.56). CONCLUSIONS: Albumin 20% was an effective volume expander in patients at 1 week post-burn. No relevant differences were found between burn patients and healthy volunteers. TRIAL REGISTRATION: EudraCT 2016-000996-26 on May 31, 2016.
Assuntos
Queimaduras/complicações , Síndrome de Vazamento Capilar/etiologia , Substitutos do Plasma/farmacologia , Adulto , Queimaduras/tratamento farmacológico , Queimaduras/fisiopatologia , Síndrome de Vazamento Capilar/tratamento farmacológico , Síndrome de Vazamento Capilar/prevenção & controle , Feminino , Humanos , Masculino , Substitutos do Plasma/uso terapêutico , Volume Plasmático/efeitos dos fármacos , Albumina Sérica HumanaRESUMO
Hypersensitivity reactions to drugs may cause very rapid physiologic derangements that can be fatal in the absence of adequate compensatory mechanisms or definitive treatment. For the most part, adverse drug reactions that progress over the course of minutes are mediated either by mast cell or complement activation. If a patient survives the acute event, appropriate long-term management requires the identification and future avoidance of the inciting drug. Here, we describe a patient who experienced two life-threatening multisystem reactions with cardiopulmonary compromise minutes after taking hydrochlorothiazide (HCTZ). The reactions were associated with systemic vascular leak resulting in hypotension and non-cardiogenic pulmonary edema.
Assuntos
Síndrome de Vazamento Capilar/etiologia , Hidroclorotiazida/efeitos adversos , Síndrome de Vazamento Capilar/complicações , Parada Cardíaca/tratamento farmacológico , Parada Cardíaca/etiologia , Humanos , Hidroclorotiazida/uso terapêutico , Masculino , Pessoa de Meia-IdadeRESUMO
Neonatal capillary leak syndrome is a clinical syndrome with definite etiology or predisposing factors and has the manifestations of hypotension, hemoconcentration, hypoproteinemia, and systemic edema. This disease often has critical conditions and may lead to multiple organ failure and even death. There are still controversies over the diagnosis and treatment of this disease. This article summarizes the recent advances in the diagnosis and treatment of neonatal capillary leak syndrome, in order to improve the diagnosis and treatment of this disease among clinicians.
Assuntos
Síndrome de Vazamento Capilar , Síndrome de Vazamento Capilar/diagnóstico , Síndrome de Vazamento Capilar/etiologia , Síndrome de Vazamento Capilar/terapia , Edema , Humanos , Hipoproteinemia , Insuficiência de Múltiplos ÓrgãosRESUMO
Extracorporeal circulation can be accompanied by increased vascular permeability leading to pathological fluid balance and organ dysfunction. The second messenger cAMP is involved in capillary permeability and maintains endothelial integrity. The aim of the present study was to evaluate the effect of phosphodiesterase-4 (PDE4) inhibition with rolipram on extracorporeal circulation-induced capillary leakage, microcirculatory dysfunction, and organ injury in rodents. Rats were randomly allocated to the following groups: sham ( n = 5), venoarterial extracorporeal circulation [extracorporeal life support (ECLS), n = 7], ECLS + rolipram ( n = 7), extracorporeal resuscitation (ECPR; n = 7), and ECPR + rolipram ( n = 7). In the groups that underwent ECPR, ECLS-based cardiopulmonary resuscitation (ECPR) was performed after the induction of hypoxic cardiac arrest. Upon return of spontaneous circulation, rolipram was administered intravenously. The mesenteric microcirculation was studied using intravital microscopy, and organ specimens were harvested upon completion of the study. ECLS and ECPR induced a proinflammatory response (cytokines IL-1ß, IL-6, and TNF-α). Although PDE4 expression was upregulated in vascular tissue, PDE4 inhibition abrogated impaired microcirculation and capillary leak (albumin extravasation of the sham group: 1 ± 0.03-fold, ECLS group: 1.2 ± 0.05-fold, ECLS + rolipram group: 0.99 ± 0.04-fold, ECPR group: 1.6 ± 0.04-fold, and ECPR + rolipram group: 1.06 ± 0.02-fold from the sham group, P < 0.05). PDE4 inhibition led to stabilization of vascular cAMP levels but did not affect cytokine levels. Capillary leak was reduced, as demonstrated by the decrease of the systemic biomarkers soluble vascular-endothelial cadherin and activated complement 3. Histological analysis revealed reduced injury to the lungs and kidneys after PDE4 inhibition, with a significant decrease in systemic renal damage markers. Our findings demonstrate that extracorporeal circulation causes an inflammatory reaction associated with decreased vascular cAMP levels, increased vascular permeability, and impaired microcirculation. PDE4 inhibition proved to be capable of reducing these side effects in ECLS and ECPR, leading to reduced microcirculatory, renal, and pulmonary injury. NEW & NOTEWORTHY Various complications are common after extracorporeal circulation. Among these, endothelial injury may cause impaired microcirculation and capillary leak. Here, we report that phosphodiesterase-4 inhibition targeting endothelial cAMP is capable of reducing microvascular complications in a rodent model of extracorporeal resuscitation. Microcirculation and vascular permeability are influenced without targeting extracorporeal circulation-induced inflammation. Thus, pulmonary and renal organ protection may be conferred.
Assuntos
Permeabilidade Capilar/efeitos dos fármacos , Oxigenação por Membrana Extracorpórea/efeitos adversos , Microcirculação/efeitos dos fármacos , Inibidores da Fosfodiesterase 4/farmacologia , Animais , Síndrome de Vazamento Capilar/etiologia , Síndrome de Vazamento Capilar/prevenção & controle , Débito Cardíaco/efeitos dos fármacos , Reanimação Cardiopulmonar , AMP Cíclico/metabolismo , Nucleotídeo Cíclico Fosfodiesterase do Tipo 4/biossíntese , Citocinas/metabolismo , Masculino , Ratos , Ratos Sprague-Dawley , Ressuscitação , Rolipram/farmacologia , Sistemas do Segundo MensageiroRESUMO
BACKGROUND: We report hereby a severe case of Hantavirus Pulmonary Syndrome" (HPS) induced by Maripa virus in French Guiana and describe the mechanism of severity of the human disease. CASE PRESENTATION: A 47-year- old patient started presenting a prodromic period with fever, dyspnea, cough and head ache. This clinical presentation was followed by a rapid respiratory, hemodynamic and renal failure leading to admission in the ICU. Biological exams revealed an increased haematocrit level with a paradoxical low protein level. Echocardiographic and hemodynamic monitoring showed a normal left ventricular function with low filling pressures, an elevated extravascular lung water index and pulmonary vascular permeability index. These findings were compatible with a capillary leak-syndrome (CLS). CONCLUSIONS: The severity of HPS caused by the virus Maripa in French Guiana can be explained by the tropism of hantavirus for the microvascular endothelial cell leading to a CLS.
Assuntos
Síndrome de Vazamento Capilar/etiologia , Síndrome de Vazamento Capilar/fisiopatologia , Síndrome Pulmonar por Hantavirus/complicações , Síndrome Pulmonar por Hantavirus/fisiopatologia , Orthohantavírus/patogenicidade , Síndrome de Vazamento Capilar/diagnóstico , Guiana Francesa , Orthohantavírus/isolamento & purificação , Síndrome Pulmonar por Hantavirus/diagnóstico , Humanos , Pessoa de Meia-IdadeRESUMO
Transplant-associated thrombotic microangiopathy (TA-TMA) is one of the early endothelial complications post Hematopoietic Stem Cell Transplant (HSCT). Several mechanisms during HSCT can contribute to systemic capillary endothelial damage which can lead to TA-TMA among other complications as capillary leak syndrome or engraftment syndrome. Early diagnosis of TA-TMA contributes a challenge due to overlapping clinical manifestations and the absence of specific diagnostic criteria. Incidence is greatly variable between 1-76% according to risk factors of patients and the definition used to confirm the diagnosis. The mortality rates in patients who develop severe TA-TMA are in excess of 80%. Early treatment improves the outcome. This review outlines the diagnostic challenges and therapeutic options for TA-TMA.
Assuntos
Síndrome de Vazamento Capilar , Transplante de Células-Tronco Hematopoéticas , Microangiopatias Trombóticas , Aloenxertos , Síndrome de Vazamento Capilar/diagnóstico , Síndrome de Vazamento Capilar/etiologia , Síndrome de Vazamento Capilar/metabolismo , Síndrome de Vazamento Capilar/terapia , Humanos , Microangiopatias Trombóticas/diagnóstico , Microangiopatias Trombóticas/etiologia , Microangiopatias Trombóticas/metabolismo , Microangiopatias Trombóticas/terapiaRESUMO
BACKGROUND: Postoperative fluid management in critically ill neonates and infants with capillary leak syndrome (CLS) and extensive volume overload after cardiac surgery on cardiopulmonary bypass is challenging. CLS is often resistant to conventional diuretic therapy, aggravating the course of weaning from invasive ventilation, increasing length of stay on ICU and morbidity and mortality. METHODS: Tolvaptan (TLV, vasopressin type 2 receptor antagonist) was used as an additive diuretic in neonates and infants with CLS after cardiac surgery. Retrospective analysis of 25 patients with CLS including preoperative and postoperative parameters was performed. Multivariate regression analysis was performed to identify predictors for TLV response. RESULTS: Multivariate analysis identified urinary output during 24 h after TLV administration and mean blood pressure (BP) on day 2 of TLV treatment as predictors for TLV response (AUC = 0.956). Responder showed greater weight reduction (p < 0.0001), earlier weaning from ventilator during TLV (p = 0.0421) and shorter time in the ICU after TLV treatment (p = 0.0155). Serum sodium and serum osmolality increased significantly over time in all patients treated with TLV. CONCLUSION: In neonates and infants with diuretic-refractory CLS after cardiac surgery, additional aquaretic therapy with TLV showed an increase in urinary output and reduction in bodyweight in patients classified as TLV responder. Increase in urinary output and mean BP on day 2 of treatment were strong predictors for TLV response.
Assuntos
Antagonistas dos Receptores de Hormônios Antidiuréticos/uso terapêutico , Síndrome de Vazamento Capilar/tratamento farmacológico , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Tolvaptan/uso terapêutico , Manuseio das Vias Aéreas , Transfusão de Sangue , Peso Corporal/efeitos dos fármacos , Síndrome de Vazamento Capilar/etiologia , Síndrome de Vazamento Capilar/terapia , Diuréticos/uso terapêutico , Feminino , Hidratação , Humanos , Lactente , Recém-Nascido , Fígado/metabolismo , Masculino , Osmorregulação/efeitos dos fármacos , Complicações Pós-Operatórias/tratamento farmacológico , Estudos Retrospectivos , Sódio/sangue , Micção/efeitos dos fármacosRESUMO
Approximately 500 cases of idiopathic systemic capillary leak syndrome (Clarkson syndrome) have been reported worldwide. This life-threatening condition is characterized by episodes of increase in vascular permeability with loss of fluid into the interstitium and presents with acute onset of edema, signs of tissue hypoperfusion, hemoconcentration, and low blood protein level. It has been diagnosed mainly in middle-aged adults with a monoclonal gammopathy. We performed a systematic review of the literature on Clarkson syndrome in subjects ≤ 18 years of age. We identified 24 reports, published since 1989, providing data on 32 otherwise healthy subjects, who experienced 67 well-documented episodes of Clarkson syndrome. The condition affected more frequently girls (21, 66%) than boys, presented throughout childhood, and was preceded by a mostly viral illness in 75% of cases. A monoclonal gammopathy was never reported. Uncompensated circulatory shock, muscle compartment syndrome, acute kidney injury, pulmonary edema, and either pleural or pericardial effusion were, in decreasing order of frequency, the most common complications. Four patients died.Conclusion: Clarkson syndrome develops not only in adulthood but also in childhood. In this age group, this condition is not linked to a monoclonal gammopathy. What is Known: ⢠Clarkson syndrome is a rare condition that has been diagnosed mainly in middle-aged adults and is mostly linked to a monoclonal gammopathy. What is New: ⢠In subjects ≤ 18 years of age, Clarkson syndrome is not linked to a monoclonal gammopathy.
Assuntos
Síndrome de Vazamento Capilar/diagnóstico , Adolescente , Síndrome de Vazamento Capilar/etiologia , Síndrome de Vazamento Capilar/terapia , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Fatores de RiscoRESUMO
INTRODUCTION: Factors predictive for death from snake envenomation vary between studies, possibly due to variation in host genetic factors and venom composition. This study aimed to evaluate predictive factors for death from snake envenomation in Myanmar. METHODS: A prospective study was performed among adult patients with snakebite admitted to tertiary hospitals in Yangon, Myanmar, from May 2015 to August 2016. Data including clinical variables and laboratory parameters, management, and outcomes were evaluated. Multivariate regression analysis was performed to evaluate factors predictive for death at the time of presentation to the hospital. RESULTS: Of the 246 patients with snake envenomation recruited into the study, 225 (92%) survived and 21 (8%) died during hospitalization. The snake species responsible for a bite was identified in 74 (30%) of the patients; the majority of bites were from Russell's vipers (63 patients, 85%). The independent factors predictive for death included 1) duration from bite to arrival at the hospital >1 h (odds ratio [OR]: 9.0, 95% confidence interval [CI]: 1.1-75.2; P=0.04); 2) white blood cell counts >20 ×103 cells·µL-1 (OR: 8.9, 95% CI: 2.3-33.7; P=0.001); and 3) the presence of capillary leakage (OR: 3.7, 95% CI: 1.2-11.2; P=0.02). A delay in antivenom administration >4 h increases risk of death (11/21 deaths). CONCLUSIONS: Patients who present with these independent predictive factors should be recognized and provided with early appropriate intervention to reduce the mortality rate among adults with snake envenomation in Myanmar.
Assuntos
Síndrome de Vazamento Capilar/mortalidade , Hospitalização/estatística & dados numéricos , Mordeduras de Serpentes/mortalidade , Serpentes , Centros de Atenção Terciária , Adolescente , Adulto , Animais , Antivenenos/administração & dosagem , Síndrome de Vazamento Capilar/etiologia , Feminino , Humanos , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Mianmar/epidemiologia , Estudos Prospectivos , Fatores de Risco , Daboia , Mordeduras de Serpentes/complicações , Serpentes/classificação , Centros de Atenção Terciária/estatística & dados numéricos , Fatores de Tempo , Adulto JovemRESUMO
PURPOSE: The two life-threatening signs of anaphylactic shock (AS) are severe arterial hypotension and bronchospasm. Guidelines recommend epinephrine as first-line treatment. Arginine vasopressin (AVP) has been proposed as an alternative if epinephrine does not correct arterial hypotension. These two drugs may have beneficial, neutral or deleterious effects on airflow either directly or by modifying factors that regulate vasodilatation and/or edema in the bronchial wall. AIM OF THE STUDY: To compare the effects of epinephrine and AVP on airflow and airway leakage in a rat model of AS. MATERIALS AND METHODS: Thirty-two ovalbumin-sensitized rats were randomized into four groups: control (CON), AS without treatment (OVA), AS treated with epinephrine (EPI), and AS treated with AVP (AVP). Mean arterial pressure (MAP), respiratory resistance and elastance and microvascular leakage in the airways were measured. RESULTS: All OVA rats died within 20 minutes following ovalbumin injection. Ovalbumin induced severe arterial hypotension and airway obstruction (221 ± 36 hPa.s.L-1 vs. vehicle 52 ± 8 hPa.s.L-1; p < 0.0001) associated with microvascular leakage distributed throughout the trachea, bronchi and intra-pulmonary airways. EPI and AVP extended survival time; EPI restored a higher level of MAP than AVP. Airway obstruction was attenuated by epinephrine (146 ± 19 hPa.s.L-1; p < 0.0001), but not by AVP (235 ± 58 hPa.s.L-1; p = 0.42). CONCLUSIONS: Epinephrine was superior to AVP for alleviating the airway response in a rat model of AS. When bronchospasm and severe arterial hypotension are present during AS, epinephrine should be the drug of choice.
Assuntos
Anafilaxia/complicações , Espasmo Brônquico/etiologia , Epinefrina/farmacologia , Hipotensão/etiologia , Sistema Respiratório/patologia , Vasopressinas/farmacologia , Obstrução das Vias Respiratórias/etiologia , Animais , Pressão Arterial , Síndrome de Vazamento Capilar/etiologia , Neurofisinas/farmacologia , Ovalbumina/farmacologia , Precursores de Proteínas/farmacologia , RatosRESUMO
Objective: To study the clinical characteristics of sepsis with systemic capillary leak syndrome(SCLS) and to evaluate the therapeutic effect and clinical significance of fluid therapy adjusted timely in these patients. Methods: The clinical data of 34 patients with sepsis and SCLS in the Department of Hepatobiliary Surgery ICU of General Hospital of People's Liberation Army General Hospital from July 2014 to January 2016 were retrospectively analyzed.There were 21 males and 13 females, aged from 21 to 74 years, with an average age of 56.3 years.Primary disease as follows: 18 cases with severe acute pancreatitis, 7 postoperative cases of subtotal hepatectomy, 5 postoperative cases of pancreatoduodenectomy, 4 postoperative cases of cholelithiasis.These patients were divided into survival group and death group according to their 28-day survival status.The clinical data including C-reactive protein(CRP), platelets (PLT), brain natriuretic peptide (BNP), the level of arterial blood lactic acid(LAC), oxygenation index(PaO2/FiO2, OI), net fluid balance(NFB) and norepinephrine dosage(NE) were collected and compared between two groups at three different intervals(day 1-3, day 4-6, day 7-9). The measurement data and numeration data were statistically analyzed with t test and χ2 test respectively to explore the inherent characteristics of the disease evolution and its clinical significance. Results: The survival group (n=23)and the death group(n=11)had no significant difference in the characteristics of basic clinical characters.The condition of the survival group and the death group were both in progress in 1-3 days period manifested as increased CRP(t=-0.473, P=0.640) and BNP levels(t=0.140, P=0.895), decreased PLT counts(t=-0.505, P=0.620) in the inflammatory response, decreased LAC(t=-1.008, P=0.320) and OI level (t=-2.379, P=0.020)in tissue perfusion index, and positive fluid balance(NFB: t=0.910, P=0.370), required NE(t=-0.853, P=0.400) to maintain effective perfusion pressure with systemic edema in both groups.There was no significant difference of all these clinical parameters between the two groups.The patients' condition of the survival group reached a plateau phase, whereas all relative indicators of the death group implied significant aggravation and deterioration of systemic infection(CRP: t=-3.438, P=0.000; PLT: t=1.649, P=0.110; BNP: t=-10.612, P=0.000), tissue perfusion (LAC: t=-11.305, P=0.000; OI: t=2.743, P=0.010)and tissue edema NFB(t=-4.257, P=0.000) and NE(t=-7.956, P=0.000) in 4-6 days period.In the last 7-9 days period the patients' condition of the survival group took a turn for improvement, yet the condition of the death group continued to deteriorate, refractory septic shock developed and multiple organ dysfunction syndrome followed afterwards inevitably(CRP: t=-10.036, P=0.000; PLT: t=6.061, P=0.000; BNP: t=-10.119, P=0.000; LAC: t=-24.466, P=0.000; OI: t=13.443, P=0.010; NFB: t=-8.345, P=0.000; NE: t=-7.121, P=0.000). Conclusions: The condition of patient with sepsis and SCLS would be improved markedly at the critical turning point around 7-9 days period since the effective systemic treatment began.If the infection does not be significantly constrolled and SCLS still remains in a sustained extravasation period in 7-9 days, the prognosis of these patients may be worse and the mortality may be higher than that of the patients mentioned before.