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Hematological abnormalities are common in cirrhosis and are associated with various pathophysiological mechanisms. Studies have documented a prevalence of thrombocytopenia, leukopenia, and anemia in patients with compensated cirrhosis of 77.9%, 23.5%, and 21.1%, respectively. These abnormalities carry significant clinical implications, including considerations for invasive procedures, infection risk, bleeding risk, and prognosis. Previously, cirrhosis was believed to predispose patients to bleeding due to alterations observed in classical coagulation tests such as prothrombin time, partial thromboplastin time, international normalized ratio, and thrombocytopenia. However, this understanding has evolved, and cirrhosis patients are now also acknowledged as being at a high risk for thrombotic events. Hemostasis in cirrhosis patients presents a complex phenotype, with procoagulant and anticoagulant abnormalities offsetting each other. This multifactorial phenomenon is inadequately reflected by routine laboratory tests. Thrombotic complications are more prevalent in decompensated cirrhosis and may correlate with disease severity. Bleeding is primarily associated with portal hypertension, endothelial dysfunction, mechanical vessel injury, disseminated intravascular coagulation, endotoxemia, and renal injury. This review comprehensively outlines hematologic index abnormalities, mechanisms of hemostasis, coagulation, and fibrinolysis abnormalities, limitations of laboratory testing, and clinical manifestations of bleeding and thrombosis in patients with liver cirrhosis.
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Improvements in clinical assessment have occurred since the last published recommendations on the diagnosis and treatment of acute promyelocytic leukemia in 2013. Here, a committee of specialists of the Brazilian Association of Hematology, Hemotherapy and Cellular Therapy presents a comprehensive review on the current knowledge, focusing on the advances in diagnosis, risk assessment, and frontline and salvage therapy. The concept of urgent diagnosis is explored as well as the management of critical situations such as coagulopathy and differentiation syndrome. Recent adjustments in risk stratification based on white blood cell counts only are presented together with the incorporation of chemo-free regimens for non-high-risk patients. Special conditions such as acute promyelocytic leukemia in children, the elderly and pregnant women are discussed. Finally, acute promyelocytic leukemia is presented as a highly curable disease because of the real possibility of targeted therapy towards differentiation, and, paradoxically, as a serious and urgent condition that deserves prompt recognition and management to avoid early mortality.
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This case report presents an exotic envenomation by a Chinese snake, Protobothrops mangshanensis. Its venom exhibited potent activity against plasma and fibrinogen, among other enzymatic activities. The patient initially presented with edema of the right upper limb, without tissue necrosis. There were no signs of bleeding; however, severe hypofibrinogenemia was observed (nadir value at 0.4 g/L), with a marked increase in fibrinogen degradation products and D-dimers, without any other coagulation disturbances. In the absence of a specific antivenom available against Asian Crotalinae venoms, the patient was treated at the 29th hour after bite with six vials of Antivipmyn™ TRI (Instituto Bioclon, Mexico, Mexico), a Mexican antivenom initially intended for American Crotalinae venoms, i.e., Bothrops asper, Lachesis muta and Crotalus durissus. Fibrinogen began to rise 6 hours after the antivenom infusion and was within the normal range 38 hours later. The report also underscores the utility of ClotPro® (Haemonetics ®USA), a viscoelastic test, for real-time monitoring of the snakebite-related coagulopathy. The clotting time was extended to 188 seconds on the EX-test while the MCF was decreased to 31 mm on the EX-test and the AP-test and was not measurable on the FIB-test, confirming severe hypofibrinogenemia. In order to confirm the paraspecificity of antivenom on the venom of P. mangshanensis, we studied the experimental neutralization of the venom procoagulant effect by Antivipmyn TRI and Green Pit Viper antivenom, which has been used in previous published clinical cases of P. mangshanensis envenomation. Both Antivipmyn™ TRI and Green Pit Viper antivenom corrected the procoagulant effect induced by P. mangshanensis venom. These findings suggest that Antivipmyn™ TRI cross-reacts with Protobothrops mangshanensis venom. In the absence of antivenom covering Asian Crotalinae, Antivipmyn TRI should be considered to treat an envenomation by Protobothrops spp.
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Antivenenos , Venenos de Crotalídeos , Mordeduras de Serpentes , Antivenenos/uso terapêutico , Animais , Mordeduras de Serpentes/tratamento farmacológico , Humanos , Venenos de Crotalídeos/toxicidade , Masculino , México , França , Crotalinae , Coagulação Sanguínea/efeitos dos fármacos , FibrinogênioRESUMO
Background: Snake envenomation is a medical condition with high morbidity and mortality in southwestern Colombia. Objectives: To describe the characteristics of the envenomation caused by Viperidae snakes view in a highly complex hospital in Southwestern Colombia. Methods: A cross-sectional study was carried out. Patients treated for Viperidae snake envenomation from 2001 to 2020 in a Hospital Fundación Valle del Lili, Cali, Colombia, were studied. Results: Twenty-eight patients were included. Envenomation was caused by the genera Bothrops, Bothriechis, Porthidium, and Bothrocophias. The median age was 37.7 (±20.6), and they were predominantly male (19, 68%). Bites occurred on the upper extremities in 16 (57%) patients. Pain (23, 81%) and edema (22, 78%) were the most common clinical symptoms. Thirteen (46%) patients presented coagulopathy. Prolonged prothrombin and activated partial thromboplastin times were common: (22, 78% and 15, 53%, respectively). Twenty (71%) patients were treated with polyvalent antivenom (median dose of 6 (2-15) vials). The median time between the accident and antivenom administration was 9 h (5.5-17). Door-to-needle time was 37.5 (0-62) min. Eighteen (64%) patients were admitted to the intensive care unit. Three (11%) patients had serum sickness. Seven (25%) developed infectious complications, four (14%) had surgery, one (3%) had compartment syndrome, one (3%) underwent amputation of the affected limb, and one (3%) patient died. Conclusions: Local manifestations and coagulopathy were common clinical features. Polyvalent antivenom was an effective treatment for disease control. Significant complications were associated with delays in seeking medical care.
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Patient Blood Management (PBM) is a holistic approach to managing blood as a resource of each patient; it is a multimodal strategy that is implemented using a set of techniques that can be applied in individual cases. In fact, the overall result of the implementation of PBM cannot be fully appreciated or explained by simply summing up the effects of the individual strategies and techniques used, since they can only produce the expected ideal result if combined. Implementing a PBM program in healthcare offers several benefits including improved patient safety, better outcomes, cost savings, conservation of resources, evidence-based practice, transfusion alternatives, improved quality of care, compliance with accreditation standards, patient-centered care, and professional education and training.
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INTRODUCTION: Bothriechis schlegelii is a Crotaline viperid species of Central America and Northern South America. The characteristics of its envenomation have not been well established. We present clinical characteristics of human cases evaluated and treated in a hospital in southwestern Colombia. METHODS: We evaluated data from patients who suffered Bothriechis schlegelii envenomation and were seen at Fundación Valle del Lili Hospital, Cali, Colombia between 2011 and 2022. RESULTS: Eight patients were included, with a median age of 24 years. Snakebites occurred in rural areas. Six (75%) patients were bitten on the upper extremities in relation to the arboreal habits of this animal. The most common symptoms were pain and edema (N = 8, 100%), ecchymoses (N = 2, 25%), and paresthesia (N = 2, 25%). The most common systemic findings were hypofibrinogenemia (N = 8, 100%) and prolonged prothrombin time in five patients (N = 5, 62.5%). All were treated with polyvalent antivenom for Colombian snakes, with a good response and outcome. CONCLUSIONS: Most bite sites from B. schlegelii were on the upper limbs. All patients had both local manifestations, including edema, pain, and systemic effects with hypofibrinogenemia, but none had systemic bleeding. Every patient received antivenom and had favorable outcomes.
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Afibrinogenemia , Bothrops , Crotalinae , Animais , Humanos , Adulto Jovem , Adulto , Colômbia/epidemiologia , Antivenenos/uso terapêutico , Dor/tratamento farmacológico , Dor/etiologia , Edema/etiologiaRESUMO
Snakebite envenomation is classified as a Neglected Tropical Disease. Bothrops jararaca venom induces kidney injury and coagulopathy. HF3, a hemorrhagic metalloproteinase of B. jararaca venom, participates in the envenomation pathogenesis. We evaluated the effects of HF3 in mouse kidney and blood plasma after injection in the thigh muscle, mimicking a snakebite. Transcriptomic analysis showed differential expression of 31 and 137 genes related to kidney pathology after 2 h and 6 h, respectively. However, only subtle changes were observed in kidney proteome, with differential abundance of 15 proteins after 6 h, including kidney injury markers. N-terminomic analysis of kidney proteins showed 420 proteinase-generated peptides compatible with meprin specificity, indicating activation of host proteinases. Plasma analysis revealed differential abundance of 90 and 219 proteins, respectively, after 2 h and 6 h, including coagulation-cascade and complement-system components, and creatine-kinase, whereas a semi-specific search of N-terminal peptides indicated activation of endogenous proteinases. HF3 promoted host reactions, altering the gene expression and the proteolytic profile of kidney tissue, and inducing plasma proteome imbalance driven by changes in abundance and proteolysis. The overall response of the mouse underscores the systemic action of a hemorrhagic toxin that transcends local tissue damage and is related to known venom-induced systemic effects.
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Bothrops , Venenos de Crotalídeos , Camundongos , Animais , Proteoma , Multiômica , Metaloproteases/metabolismo , Venenos de Serpentes/toxicidade , Peptídeos , Plasma/metabolismo , Rim/metabolismo , Bothrops/metabolismo , Venenos de Crotalídeos/toxicidade , Venenos de Crotalídeos/metabolismoRESUMO
Venom-induced consumption coagulopathy and thrombocytopenia are common and potentially severe manifestations of viperid snakebite envenoming since they contribute to local and systemic hemorrhage. Therefore, the assessment of the efficacy of antivenoms to neutralize coagulopathic and thrombocytopenic toxins should be part of the preclinical evaluation of these drugs. To evaluate the efficacy of the polyvalent (Crotalinae) antivenom produced in Costa Rica, in this study we have used a mouse model of coagulopathy and thrombocytopenia induced by the venom of Bothrops asper, based on the bolus intravenous (i.v.) injection of venom. When venom and antivenom were incubated before injection, or when antivenom was administered i.v. immediately after venom injection, venom-induced hemostatic alterations were largely abrogated. We also studied the recovery rate of clotting parameters in conditions where antivenom was administered when mice were coagulopathic. Some parameters recovered more rapidly in antivenom-treated mice than in control envenomed animals, but others showed a spontaneous recovery without antivenom. This is due to a rapid clearance of plasma venom levels in these experimental conditions. This implies that models based on the bolus i.v. injection of venom have limitations for assessing the effect of antivenom in the recovery of clotting alterations once coagulopathy has developed. It is suggested that alternative models should be developed based on a slower systemic absorption of venom. Overall, our findings provide a protocol for the preclinical evaluation of antivenoms and demonstrate that the polyvalent antivenom is effective in neutralizing the toxins of B. asper venom responsible for coagulopathy and thrombocytopenia.
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Background: Twenty-minute whole blood clotting test (20WBCT) and Modified Lee and White (MLW) method are the most routinely employed bedside tests for detecting coagulopathic snake envenomation. Our study compared the diagnostic utility of MLW and 20WBCT for snakebite victims at a tertiary care hospital in Central Kerala, South India. Methods: This single-center study recruited 267 patients admitted with snake bites. 20WBCT and MLW were performed simultaneously at admission along with the measurement of Prothrombin Time (PT). The diagnostic utility of 20WBCT and MLW was determined by comparing the sensitivity (Sn), specificity (Sp), positive and negative predictive values, likelihood ratios, and accuracy at admission with an INR value > 1.4. Results: Out of 267 patients, 20 (7.5%) patients had VICC. Amongst those who had venom-induced consumption coagulopathy (VICC), MLW was prolonged for 17 patients, (Sn 85% 95% confidence interval [CI]: 61.1-96.0) whereas 20WBCT was abnormal for 11 patients (Sn 55%, 95% CI: 32.04-76.17). MLW and 20WBCT were falsely positive for the same patient (Sp 99.6%, 95% CI: 97.4-99.9%). Conclusion: MLW is more sensitive than 20WBCT to detect coagulopathy at the bedside amongst snakebite victims. However, further studies are necessary for standardizing bedside coagulation tests in snakebite cases.
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Sepsis syndrome is a highly lethal uncontrolled response to an infection, which is characterized by sepsis-induced coagulopathy (SIC). High-density lipoprotein (HDL) exhibits antithrombotic activity, regulating coagulation in vascular endothelial cells. Sepsis induces the release of several proinflammatory molecules, including reactive oxygen species, which lead to an increase in oxidative stress in blood vessels. Thus, circulating lipoproteins, such as HDL, are oxidized to oxHDL, which promotes hemostatic dysfunction, acquiring prothrombotic properties linked to the severity of organ failure in septic-shock patients (SSP). However, a rigorous and comprehensive investigation demonstrating that oxHDL is associated with a coagulopathy-associated deleterious outcome of SSP, has not been reported. Thus, we investigated the participation of plasma oxHDL in coagulopathy-associated sepsis pathogenesis and elucidated the underlying molecular mechanism. A prospective study was conducted on 42 patients admitted to intensive care units, (26 SSP and 16 non-SSP) and 39 healthy volunteers. We found that an increased plasma oxHDL level in SSP was associated with a prothrombotic phenotype, increased mortality and elevated risk of death, which predicts mortality in SSP. The underlying mechanism indicates that oxHDL triggers an endothelial protein expression reprogramming of coagulation factors and procoagulant adhesion proteins, to produce a prothrombotic environment, mainly mediated by the endothelial LOX-1 receptor. Our study demonstrates that an increased plasma oxHDL level is associated with coagulopathy in SSP through a mechanism involving the endothelial LOX-1 receptor and endothelial protein expression regulation. Therefore, the plasma oxHDL level plays a role in the molecular mechanism associated with increased mortality in SSP.
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Abstract Background: Twenty-minute whole blood clotting test (20WBCT) and Modified Lee and White (MLW) method are the most routinely employed bedside tests for detecting coagulopathic snake envenomation. Our study compared the diagnostic utility of MLW and 20WBCT for snakebite victims at a tertiary care hospital in Central Kerala, South India. Methods: This single-center study recruited 267 patients admitted with snake bites. 20WBCT and MLW were performed simultaneously at admission along with the measurement of Prothrombin Time (PT). The diagnostic utility of 20WBCT and MLW was determined by comparing the sensitivity (Sn), specificity (Sp), positive and negative predictive values, likelihood ratios, and accuracy at admission with an INR value > 1.4. Results: Out of 267 patients, 20 (7.5%) patients had VICC. Amongst those who had venom-induced consumption coagulopathy (VICC), MLW was prolonged for 17 patients, (Sn 85% 95% confidence interval [CI]: 61.1-96.0) whereas 20WBCT was abnormal for 11 patients (Sn 55%, 95% CI: 32.04-76.17). MLW and 20WBCT were falsely positive for the same patient (Sp 99.6%, 95% CI: 97.4-99.9%). Conclusion: MLW is more sensitive than 20WBCT to detect coagulopathy at the bedside amongst snakebite victims. However, further studies are necessary for standardizing bedside coagulation tests in snakebite cases.
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Tempo de Protrombina/métodos , Mordeduras de Serpentes/diagnóstico , Transtornos da Coagulação Sanguínea/diagnóstico , Fatores de Coagulação Sanguínea/análiseRESUMO
Snakebite envenomation is classified as a Neglected Tropical Disease. Bothrops jararaca venom induces kidney injury and coagulopathy. HF3, a hemorrhagic metalloproteinase of B. jararaca venom, participates in the envenomation pathogenesis. We evaluated the effects of HF3 in mouse kidney and blood plasma after injection in the thigh muscle, mimicking a snakebite. Transcriptomic analysis showed differential expression of 31 and 137 genes related to kidney pathology after 2 h and 6 h, respectively. However, only subtle changes were observed in kidney proteome, with differential abundance of 15 proteins after 6 h, including kidney injury markers. N-terminomic analysis of kidney proteins showed 420 proteinase-generated peptides compatible with meprin specificity, indicating activation of host proteinases. Plasma analysis revealed differential abundance of 90 and 219 proteins, respectively, after 2 h and 6 h, including coagulation-cascade and complement-system components, and creatine-kinase, whereas a semi-specific search of N-terminal peptides indicated activation of endogenous proteinases. HF3 promoted host reactions, altering the gene expression and the proteolytic profile of kidney tissue, and inducing plasma proteome imbalance driven by changes in abundance and proteolysis. The overall response of the mouse underscores the systemic action of a hemorrhagic toxin that transcends local tissue damage and is related to known venom-induced systemic effects.
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Introducción: Los trastornos de la coagulación durante el perioperatorio de pacientes oncológicos, son eventos más frecuentes de lo que se conoce en realidad, debido a que un gran número de estos transitan de forma inadvertida. Objetivo: Describir los factores fisiopatológicos que propician la ocurrencia de las coagulopatías adquiridas por consumo durante el perioperatorio del paciente oncológico. Métodos: Se realizó una revisión narrativa, en idiomas español e inglés, se utilizaron como fuente de búsqueda las bases de datos Ebsco, SciElo, Pubmed, Cubmed, Hinary, durante el período de enero a marzo de 2022, y el referenciador Zotero versión 5.0. Resultados: Para comprender qué pasa en el paciente con cáncer en relación con las coagulopatías por consumo es necesario entender la fisiología de los mecanismos de la coagulación. En este sentido, se pueden observar tanto trastornos trombóticos como hemorrágicos, por el incremento del factor tisular que determina la formación de trombina y el fallo de los mecanismos antifibrinolíticos. También, factores como la radioterapia, la quimioterapia y la transfusión de hemocomponentes, aumentan el riesgo de padecerlas. Conclusiones: la coagulopatía por consumo en el paciente oncológico es una entidad multifactorial, compleja y dinámica, en la que se debe pensar y diagnosticar para evitar complicaciones graves en el período perioperatorio.
Introduction: Coagulation disorders during the perioperative period of cancer patients are more frequent events than is actually known, due to the fact that a large number of these go unnoticed. Objective: To describe the pathophysiological factors that favor the occurrence of consumption-acquired coagulopathies during the perioperative period of cancer patients. Methods: A narrative review was carried out, in Spanish and English, using the Ebsco, Scielo, Pubmed, Cubmed, Hinary databases as a search source, during the period from January to March 2022, and the Zotero version 5.0 referer. 96.3. Results: To understand what happens in cancer patients in relation to consumption coagulopathies, it is necessary to understand the physiology of coagulation mechanisms. In this sense, both thrombotic and hemorrhagic disorders can be observed, due to the increase in the tissue factor that determines the formation of thrombin and the failure of antifibrinolytic mechanisms. Also, factors such as radiotherapy, chemotherapy and transfusion of blood components, increase the risk of suffering from them. Conclusions: consumption coagulopathy in cancer patients is a multifactorial, complex and dynamic entity, which must be considered and diagnosed to avoid serious complications in the perioperative period.
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Humanos , Coagulação Intravascular Disseminada/fisiopatologiaRESUMO
OBJECTIVE: The objective of this study was to determine if there are differences between the presentation patterns of hemorrhagic stroke (HS) associated to COVID-19. METHODS: It was performed a systematic search based on PRISMA guidelines of the cases reported in PUBMED of HS associated to SARS-CoV-2 infection and we added to this sample cases from our own hospital cohort. Patients in the database were separated by groups according to presentation symptoms: if they debuted with neurological symptoms or debuted with pulmonary symptoms. RESULTS: Seventy cases were included in the study. Patients that debuted with pulmonary symptoms accounted for 68.6% of the cases with an interval between the development of symptoms and the presentation of HS of 15.6 days. We found that the use of anticoagulants during hospitalization, multifocal image pattern, and the elevation of D-dimer, Ferritin, and lactate dehydrogenase levels were significantly associated with the group of pulmonary presentation, whereas the presence of hypertension during hospitalization, and a lower hemoglobin level was associated with the group of neurologic symptoms. CONCLUSION: Although HS associated with COVID-19 is a clinical entity with increasing evidence, it is necessary to establish that there are two forms of presentation with their own characteristics.
OBJETIVO: determinar si existen diferencias entre los patrones de presentación de hemorragia intracraneal asociada a COVID-19. PACIENTES Y MÉTODOS: Se realizó una búsqueda sistemática basada en la guía PRISMA de los casos reportados en PUBMED de hemorragia intracraneal asociados a infección por SARS-CoV-2 y se agregaron a esta muestra casos de nuestra propia cohorte hospitalaria. RESULTADOS: se incluyeron 70 casos. Los pacientes que debutaron con síntomas pulmonares representaron el 68.6% de los casos con un intervalo entre el desarrollo de los síntomas y la presentación de la hemorragia intracraneal de 15.6 días. Encontramos que el uso de anticoagulantes durante la hospitalización, el patrón de imagen multifocal y la elevación de los niveles de dímero D, ferritina y deshidrogenasa láctica se asociaron significativamente con el grupo de presentación pulmonar, mientras que la presencia de hipertensión durante la hospitalización, y un nivel de hemoglobina más bajo se asoció con el grupo que debutó con síntomas neurológicos. CONCLUSIÓN: si bien la hemorragia intracraneal asociada a COVID-19 es una entidad clínica con evidencia creciente, es necesario establecer que existen dos formas de presentación con características propias.
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COVID-19 , Humanos , Hemorragia Cerebral/epidemiologia , Hemorragia Cerebral/etiologia , COVID-19/complicações , SARS-CoV-2RESUMO
The presence of thrombotic events in COVID-19 patients has been described since the beginning of the pandemic. This association has been confirmed in most of the reported studies. Autopsy reports have shown that most thromboses are located in the lung, although they have also been observed in other organs such as the skin and kidneys. SARS-CoV2 infection induces a generalized prothrombotic state, which is attributed to a combination of factors such as hypoxia, excess cellular apoptosis, and mainly to overactivation of the immune system. Among immune-mediated prothrombotic situations, antiphospholipid syndrome (APS) stands out. Recurrent thrombotic events are observed in APS in the presence of antiphospholipid antibodies (aPL). There are numerous studies that report high prevalence of aPL in patients with COVID-19 infection. However, the results show discrepancies in the data on the prevalence of aPL, and its role in the pathogenesis of thrombosis in these patients. This could be due to the heterogeneity of the detection procedures for aPL or to transient elevations of non-pathogenic aPL levels in the context of infection. In this review we try to clarify the role of aPL in COVID-19 infection, and attempt to answer the question of whether it is a coagulopathy of its own, or secondary to APS.
La presencia de eventos trombóticos en los pacientes con COVID-19 se describió desde el inicio de la pandemia, asociación que ha sido confirmada en la mayoría de los estudios reportados. Los informes de necropsias han puesto de manifiesto que la mayoría de las trombosis se localiza en el pulmón, aunque también se han observado en otros órganos, como la piel y los riñones. La infección por SARS-CoV-2 induce un estado protrombótico generalizado que se atribuye a una conjunción de factores como la hipoxia, el exceso de apoptosis celular y, sobre todo, una hiperactivación del sistema inmune. Entre las situaciones protrombóticas inmunomediadas destaca el síndrome antifosfolipídico, en el cual se observan eventos trombóticos de repetición en presencia de anticuerpos antifosfolipídicos (AAF). Existen numerosos estudios que reportan una elevada prevalencia de AAF en los pacientes con infección por la COVID-19; sin embargo, los resultados muestran discordancias en los datos de prevalencia de AAF y su rol en la patogenia sobre la trombosis en estos pacientes, lo que que podría deberse a la heterogeneidad de los procedimientos de detección de los AAF o a elevaciones transitorias de los niveles de AAF no patogénicos en el contexto de la infección. En esta revisión se busca aclarar el papel de los AAF en la infección por COVID-19, intentando responder a la pregunta de si se trata de una coagulopatía propia o es secundaria a un síndrome antifosfolipídico.
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Humanos , Fosfatidilgliceróis , Doenças Autoimunes , Cardiolipinas , Síndrome Antifosfolipídica , Doenças do Sistema Imunitário , Lipídeos , Lipídeos de MembranaRESUMO
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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The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent driving the current COVID-19 pandemic. The acute respiratory distress that occurs in some severe COVID-19 cases has been linked with hypercoagulation or thrombotic events as well as a worse prognosis and increased risk of death. Thus, point-of-care devices that can be used for early detection of coagulation abnormalities would assist in COVID-19 management. This chapter describes the use of the Roche Diagnostics CoaguChek® XS test kit for potential use in COVID-19 personalized medicine approaches.
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COVID-19 , Coagulação Sanguínea , COVID-19/diagnóstico , Humanos , Pandemias , Sistemas Automatizados de Assistência Junto ao Leito , SARS-CoV-2RESUMO
The COVID-19 pandemic, caused by SARS-CoV-2, had its first cases identified in late 2019 and was considered a clinical pandemic in March 2020. In March 2022, more than 500 million people were infected and 6,2 million died as a result of this disease, increasingly associated with changes in human hemostasis, such as hypercoagulation. Numerous factors contribute to the hypercoagulable state, and endothelial dysfunction is the main one, since the activation of these cells can strongly activate platelets and the coagulation system. In addition, there is a dysregulation of the renin-angiotensin system due to the SARS-CoV-2 takeover of the angiotensin converting enzyme 2, resulting in a strong immune response that could further damage the endothelium. Thrombus formation in the pulmonary microvasculature structure in patients with COVID-19 is an important factor to determine the severity of the clinical picture and the outcome of this disease. This review describes the hemostatic changes that occur in SARS-CoV-2 infection, to further improve our understanding of pathogenic mechanisms and the interaction between endothelium dysfunction, kallikrein-kinins, renin angiotensin, and the Coagulation/fibrinolysis systems as underlying COVID-19 effectors. This knowledge is crucial for the development of new effective therapeutic approaches, attenuating the severity of SARS-CoV-2's infection and to reduce the deaths.
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COVID-19 , Hemostasia , Humanos , Pandemias , Peptidil Dipeptidase A/metabolismo , Sistema Renina-Angiotensina/fisiologia , SARS-CoV-2RESUMO
Viperid snakebite envenoming is often characterized by a venom-induced consumption coagulopathy due to the procoagulant effect of venom components, resulting in the alteration of clotting laboratory tests. There is a growing trend to use rotational thromboelastometry in the assessment of clotting disturbances in a variety of pathologies, although its use in experimental models of envenoming has been limited. An in vivo murine model was implemented to assess the coagulopathy induced by three Central American viperid venoms which have different mechanisms of action on clotting factors, i.e., Bothrops asper, Crotalus simus and Bothriechis lateralis. Venom was injected by the intravenous route and blood samples were collected at 1, 3, 5 and 24 h after envenoming. Coagulopathy was assessed by standard clotting tests and by routine rotational thromboelastometric parameters. In addition, the changes in platelet number were followed. B. asper and C. simus venoms induced coagulopathy and thrombocytopenia 1 h after injection, followed by a slow recovery at 3, 5 and 24 h, although the majority of clotting parameters were still significantly affected by 3 and 5 h, and were corrected by 24 h. In general, a similar time-course of alterations was observed for standard clotting tests and most rotational thromboelastomeric assays. However, some thromboelastometric parameters, especially those related to Fibtem, showed more drastic alterations than standard tests and remained altered even at 24 h in some cases. This is likely related to the low fibrinogen concentration observed at most time intervals. B. lateralis venom did not induce a consumption coagulopathy, although it caused a marked thrombocytopenia.
Assuntos
Transtornos da Coagulação Sanguínea , Venenos de Crotalídeos , Coagulação Intravascular Disseminada , Mordeduras de Serpentes , Viperidae , Animais , Antivenenos/farmacologia , Transtornos da Coagulação Sanguínea/etiologia , Testes de Coagulação Sanguínea , Venenos de Crotalídeos/toxicidade , Camundongos , Mordeduras de Serpentes/complicações , Venenos de Serpentes/toxicidade , TromboelastografiaRESUMO
Introducción: el accidente ofídico es una intoxicación ocasionada por la inoculación de veneno a través de la mordedura de una serpiente, la cual genera alteraciones locales y sistémicas. Dicho evento representa un importante problema de salud pública en los países en vía de desarrollo debido a su alta frecuencia y gravedad. Las serpientes del género Bothrops son responsables de la mayoría de los accidentes y esto se debe, en parte, a su amplia distribución geográfica y comportamiento agresivo cuando se sienten amenazadas. La lesión renal aguda es una causa importante de mortalidad en pacientes con mordedura de serpientes de este género. Objetivo: describir el caso de un paciente femenino con lesión renal aguda inducida por mordedura de serpiente del género Bothrops. Simultáneamente se detallan los datos epidemiológicos más relevantes de dicha entidad, sus factores de riesgo, los posibles mecanismos fisiopatológicos que explican la génesis de la misma, su diagnóstico y manejo clínico. Se resalta la importancia de su identificación precoz y tratamiento oportuno. Presentación del caso: se presenta el caso de una paciente de 40 años que ingresa a una institución de cuarto nivel de complejidad por presentar lesión renal aguda y coagulopatía por consumo secundario a mordedura de serpiente del género Bothrops, con presencia de sangrado vaginal y hematuria que progresa a anuria y hematemesis, requiriendo transfusión de hemoderivados y terapia de reemplazo renal, medidas con las cuales presentó una evolución clínica favorable. Discusión y conclusión: la lesión renal aguda asociada a la mordedura de serpientes del género Bothrops es una complicación clínica común y potencialmente mortal que no debe ser olvidada. Los eventos fisiopatológicos responsables de esta complicación incluyen mecanismos inmunológicos, trastornos de la coagulación, pigmenturia, nefrotoxicidad directa y la respuesta inflamatoria con efectos hemodinámicos sistémicos y renales. Se hace imprescindible el conocimiento de dicha entidad en aras de reconocerla de forma precoz e instaurar su tratamiento oportuno con el fin de reducir sus complicaciones potencialmente fatales.
Introduction: The ophidian accident is an intoxication caused by the inoculation of venom through the bite of a snake, which generates local and systemic alterations. This event represents an important public health problem in developing countries due to its high frequency and severity. Snakes of the genus Bothrops are responsible for the majority of accidents, and this is partly due to their wide geographic distribution and aggressive behavior when threatened. Acute kidney injury is an important cause of mortality in patients with snake bites of this genus. Purpose: To describe the case of a female patient with bothrops snakebite-induced acute kidney injury. Simultaneously, the most relevant epidemiological data of said entity, its risk factors, the possible pathophysiological mechanisms that explain its genesis, its diagnosis and clinical management are detailed. The importance of its early identification and timely treatment is highlighted. Case presentation: We present the case of a 40-year-old female patient who was admitted to a fourth level of complexity institution due to acute kidney injury and consumption coagulopathy secondary to bothrops snakebite, with the presence of vaginal bleeding and hematuria that progressed to anuria. and hematemesis; requiring transfusion of blood products and renal replacement therapy, measures with which she presented a favorable clinical evolution. Conclusion and discussion: Acute kidney injury associated with the bite of bothrops snakes is a common and life-threatening clinical complication that should not be overlooked. The pathophysiological events responsible for this complication include immunological mechanisms, coagulation disorders, pigmenturia, direct nephrotoxicity, and the inflammatory response with systemic and renal hemodynamic effects. Knowledge of this entity is essential in order to recognize it early and establish its timely treatment in order to reduce its potentially fatal complications.