Research Progress of Carboxymethyl Chitosan-Based Haemostatic Materials and Their Haemostatic Mechanism --Review / 中国实验血液学杂志

Effective haemostatic materials can quickly control bleeding and achieve the purpose of saving patients' lives. In recent years, chitosan-based haemostatic materials have shown good haemostatic effects, but their application is limited because chitosan is almost insoluble in water. Carboxymethyl chitosan-based haemostatic materials can promote hemostasis by activating red blood cells and aggregating platelets. In addition, carboxymethyl chitosan can bind with Ca2+ to activate platelets and coagulation factors, and start endogenous coagulation pathways, which can adsorb fibrinogen in plasma to promote haemostasis. In this paper, the latest research progress of carboxymethyl chitosan-based haemostatic materials and their haemostatic mechanism were reviewed, in order to further strengthen the understanding of the haemostatic mechanism of carboxymethyl chitosan-based haemostatic materials, and provide new idea for the research and clinical application of carboxymethyl chitosan-based haemostatic materials.

The role of Angiology and Vascular Surgery in the COVID-19 pandemic / A atuação da Angiologia e da Cirurgia Vascular na pandemia de COVID-19

ABSTRACT The New Coronavirus Epidemic (2019-nCoV), discovered in the city of Wuhan, China, in December 2019, presents mainly with pulmonary pneumonia that is preceded by fever, cough and myalgia. However, as the disease spread globally and the number of hospitalizations increased exponentially, it was noted that most serious patients hospitalized by COVID-19 have laboratory changes worthy of attention, such as lymphopenia, neutrophilia, increased time of prothrombin and increased levels of D-dimer. Due to these changes proving to be crucial for the mortality and morbidity rates in this subset of infected people, several studies focusing on the pathophysiology, mainly hematological, of the disease appear every day. Deepening these studies, several published works have shown SarsCoV-2 infection to the installation of a prothrombotic state in hospitalized patients, which leads to the potential occurrence of thrombotic or arterial events in this cohort. Thus, in order to understand how the departments of Angiology and Vascular Surgery are acting in the context of the COVID-19 pandemic, this work aims to gather studies that reveal from protocols applied in vascular services in the current situation, until to the role of vascular surgeons and angiologists in the clinical and surgical management of patients infected or not, as a way of helping and clarifying this specialty during the context of a pandemic due to the new coranavirus. For the selection of works, the following search criteria were used: "Coronavirus and venous thrombosis", "Coronavirus and thrombosis", "COVID-19 and venous thrombosis" and "COVID-19 Coronavirus and thrombosis".

RESUMO A epidemia pelo novo Coronavirus (2019-nCoV), surgido na cidade de Wuhan, na China, em dezembro de 2019, quando sintomática, apresenta-se majoritariamente por um quadro de pneumonia pulmonar que é precedida por febre, tosse seca e mialgia. No entanto, conforme a doença se espalhou globalmente e o número de hospitalizações aumentaram de forma exponencial, notou-se que a maior parte dos pacientes graves internados por COVID-19 possuem alterações laboratoriais dignas de atenção, como linfopenia, neutrofilia, aumento do tempo de protrombina e elevação dos níveis de D-dímero. Devido tais mudanças se mostrarem cruciais para a taxa de mortalidade e morbidade nesse subgrupo de infectados, diversos trabalhos com enfoque na fisiopatologia, principalmente hematológica, da doença surgem a cada dia. Aprofundando em tais estudos, variados trabalhos publicados evidenciaram a infecção pelo Sars-CoV-2 à instalação de um estado pró-trombótico em pacientes hospitalizados graves, o que acarreta em potencial ocorrência de eventos trombóticos venosos ou arteriais nessa coorte. Assim, para entender como os Departamentos de Angiologia e Cirurgia Vascular estão atuando no contexto da pandemia de COVID-19, este estudo tem por objetivo reunir estudos que revelam desde protocolos aplicados nos serviços vasculares na atual conjuntura, até a atuação dos cirurgiões vasculares e angiologistas no manejo clínico e cirúrgico de pacientes infectados ou não, como forma de ajudar e esclarecer essa especialidade durante o contexto de pandemia pelo novo coronavírus. Para a seleção dos trabalhos foram utilizados os seguintes critérios de busca: "Coronavirus and venous thrombosis", "Coronavirus and thrombosis", "COVID-19 and venous thrombosis" e "COVID-19 Coronavirus and thrombosis".

Impact of arterial procedures on coagulation and fibrinolysis - a pilot study

Abstract Objective: The main goal of our study was to assess the impact of vascular procedures on the activity of hemostatic and fibrinolytic pathways. Methods: We enrolled 38 patients with ≥ 45 years old undergoing surgery for abdominal aortic aneurysm or peripheral artery disease under general or regional anesthesia and who were hospitalized at least one night after the procedure. Patients undergoing carotid artery surgery and those who had acute bypass graft thrombosis, cancer, renal failure defined as estimated glomerular filtration rate < 30 ml/min/1.73m2, venous thromboembolism three months prior to surgery, or acute infection were excluded from the study. We measured levels of markers of hemostasis (factor VIII, von Willebrand factor:ristocetin cofactor [vWF:CoR], antithrombin), fibrinolysis (D-dimer, tissue plasminogen activator [tPA], plasmin-antiplasmin complexes), and soluble cluster of differentiation 40 ligand (sCD40L) before and 6-12h after vascular procedure. Results: Significant differences between preoperative and postoperative levels of factor VIII (158.0 vs. 103.3, P<0.001), antithrombin (92.1 vs. 74.8, P<0.001), D-dimer (938.0 vs. 2406.0, P=0.005), tPA (10.1 vs. 12.8, P=0.002), and sCD40L (9092.9 vs. 1249.6, P<0.001) were observed. There were no significant differences between pre- and postoperative levels of vWF:CoR (140.6 vs. 162.8, P=0.17) and plasmin-antiplasmin complexes (749.6 vs. 863.7, P=0.21). Conclusion: Vascular surgery leads to significant alterations in hemostatic and fibrinolytic systems. However, the direction of these changes in both pathways remains unclear and seems to be different depending on the type of surgery. A study utilizing dynamic methods of coagulation and fibrinolysis assessment performed on a larger population is warranted.

Platelet function, coagulation and fibrinolysis in patients with previous coronary and cerebrovascular ischemic events

OBJECTIVES: Ischemic stroke (IS) or transient ischemic attack (TIA) history is present in 4-17% of patients with coronary artery disease (CAD). This subgroup of patients is at high risk for both ischemic and bleeding events. The aim of this study was to determine the role of platelet aggregability, coagulation and endogenous fibrinolysis in patients with CAD and previous IS or TIA. METHODS: A prospective case-control study that included 140 stable CAD patients divided into two groups: the CASE group (those with a previous IS/TIA, n=70) and the CONTROL group (those without a previous IS/TIA, n=70). Platelet aggregability (VerifyNow Aspirin® and VerifyNow P2Y12®), coagulation (fibrinogen and thromboelastography by Reorox®) and endogenous fibrinolysis (D dimer and plasminogen activator inhibitor-1) were evaluated. RESULTS: Patients in the CASE group presented significantly higher systolic blood pressure levels (135.84±16.09 vs 123.68±16.11, p<0.01), significantly more previous CABG (25.71% vs 10%, p=0.015) and significantly higher calcium channel blocker usage (42.86% vs 24.29%, p=0.02) than those in the control group. In the adjusted models, low triglyceride values, low hemoglobin values and higher systolic blood pressure were significantly associated with previous IS/TIA (CASE group). Most importantly, platelet aggregability, coagulation and fibrinolysis tests were not independently associated with previous cerebrovascular ischemic events (CASE group). CONCLUSION: Platelet aggregability, coagulation and endogenous fibrinolysis showed similar results among CAD patients with and without previous IS/TIA. Therefore, it remains necessary to identify other targets to explain the higher bleeding risk presented by these patients.

Immunohistological study of the effect of vascular Endothelial Growth Factor on the angiogenesis of mature root canals in rat molars

Abstract Tissue bioengineering has been applied to Endodontics to seek a more biological treatment. The presence of blood vessels is crucial for cell nutrition during tissue formation. Objective This study analysed the application of vascular endothelial growth factor (VEGF) in the angiogenesis of mature root canals. Material and methods Upper first molars of twelve 13-week old Wistar male rats were used. The root pulp of the mesiobuccal canal was removed and the root canal instrumented with K-files up to size #25. Periapical bleeding was induced into the root canal by introducing a #15 K-file beyond the apex. The teeth on the right side of the arch were filled up with blood clot (G1), whereas those on the left side were filled up with blood clot plus 50 ng/ml of VEGF (G2). Teeth were sealed with light-curing glass-ionomer cement and the animals were sacrificed after 60 days. The maxilla was dissected and fixed before obtaining serial sections for histological processing with haematoxylin-eosin (HE) and immunohistochemical factor-VIII. Immunohistochemical labelling was evaluated using scores for statistical analysis. Results Immunohistological analysis demonstrated the presence of angiogenesis in both groups, but with higher angiogenic maturation in G2 during the experimental period (p<0.05). HE staining showed connective tissue with absence of odontoblasts in all specimens. Conclusions It can be concluded that it is possible to obtain angiogenesis in mature root canals with or without the use of VEGF, although the latter tends to accelerate blood vessel formation.

Generalidades del sistema de la coagulación y pruebas para su estudio / Overwiew of the Coagulation System and laboratory tests for its study

En la década de los años sesenta, se describió la cascada de la coagulación como una secuencia de eventos enzimáticos iniciada por dos vías, la intrínseca y la extrínseca, las cuales convergían en una vía común para generar una enzima multifuncional, denominada trombina. La principal función de esta enzima consistía en transformar el fibrinógeno, en fibrina, una proteína que se polimeriza espontáneamente para formar la base estructural del coágulo. Posteriormente, se propuso el Modelo Celular según el cual la coagulación no es la consecuencia de vías de activación enzimáticas secuenciales, sino de una red de interacciones entre proteínas plasmáticas y transmembranas, así como, varios tipos celulares, que permiten la formación de complejos enzimáticos altamente eficientes con la finalidad de generar trombina. Esta revisión explica en detalle ambos enfoques, además, aborda las diferentes funciones que cumple la trombina dentro de la hemostasia y los mecanismos de inhibición que regulan la coagulación. Finalmente, se describen diferentes pruebas empleadas en la actualidad para evaluar la funcionalidad del sistema de coagulación, como: el tiempo de tromboplastina parcial activado, el tiempo de protrombina, el tiempo de trombina, el tiempo de reptilasa, el tiempo de coagulación por ecarina y el uso de sustratos cromogénicos para evaluar cada factor de la coagulación. Finalmente, dado a que la generación de trombina es clave dentro de la coagulación y a que el potencial de generar trombina puede indicar propensión a desarrollar eventos trombóticos o hemorrágicos, en este trabajo se presentan los métodos existentes para determinar la generación de trombina.

In the sixties, the clotting cascade was proposed, which describes the coagulation process as a sequence of enzymatic events initiated by two different pathways, the intrinsic and the extrinsic pathways, converging on a common pathway, to generate a multifunctional enzyme, thrombin, whose main function is to convert fibrinogen into fibrin, a protein that polymerizes spontaneously to form the building block of a hemostatic clot. Later, it was proposed a cell-based model of the hemostasis according to that coagulation does not occur as a consequence of linear sequential enzyme activation pathways, but rather via a network of simultaneous interactions between plasmatic and transmembrane proteins, as well as several cellular types, that allow the formation of highly efficient enzymatic complexes that lead to thrombin generation. In this review, we summarize these two approaches highlighting the functions of thrombin within the hemostasis and the inhibition mechanisms that regulate the blood coagulation. Moreover, we described different tests that are used to assess the function of the coagulation system, such as: activated partial thromboplastin time, prothrombin time, thrombin time, reptilase time, ecarin clotting time, and the use of chromogenic substrates to evaluate individual coagulation factors. Finally, because of thrombin generation is a fundamental part of the blood coagulation and, an estimation of how well a particular individual can generate thrombin may correlate with either a risk of bleeding or thrombosis, we also include the existing methods to evaluate the potential of thrombin generation in an individual.

Antiinflamatorios no esteroides: seguridad gastrointestinal, cardiovascular y renal / Nonsteroidal antiinflammatory drugs: gastrointestinal and cardiovascular and renal safety

La selección de un medicamento específico perteneciente a una clase farmacológica es bajo criterios de eficacia, seguridad, costo y conveniencia. Los Antiinflamatorios No Esteroideos (AINEs) actualmente se constituyen en uno de los medicamentos más consumidos en el mundo, por lo tanto es de gran importancia la revisión de los aspectos de seguridad de este grupo farmacológico. El presente trabajo tiene el objetivo de analizar bajo las evidencias disponibles hasta la actualidad, la seguridad de los AINES con 3 criterios principales: gastrolesividad, cardiotoxicidad y nefrotoxicidad.

The choice of a specific medication belonging to a drug class is under the criteria of efficacy, safety, cost and suitability. NSAIDs currently constitute one of the most consumed drugs in the world, so it is very important review of the safety aspects of this drug class. This review has the objective of analyze the safety of NSAIDs on 3 main criteria: gastrolesivity, cardiotoxicity and nephrotoxicity.

El "chaco": arcilla medicinal comestible del altiplano peruano y sus propiedades en la patología digestiva / The "Chaco": eatable medicinal clay in the Peruvian highlands and his properties in digestive diseases

Los pobladores del altiplano peruano-boliviano consumen una sustancia natural conocida como "chaco", muy difundida desde la época precolombina y apreciada por sus propiedades digestivas. El Chaco es una arcilla medicinal comestible que es usada en forma de suspensión con agua para cohibir molestias dispépticas o manifestaciones ácido-pépticas. En esta contribución damos a conocer aspectos físico-químicos de la composición del Chaco, estudios experimentales en animales que evalúan su efecto antiulceroso y una prueba in vitro que estudia su propiedad antiácida. El mecanismo de acción terapéutico propuesto se debe a una acción citoprotectora sobre la mucosa gástrica por mecanismos independientes de la inhibición de la secreción ácida, ya que no posee propiedad antiácida in vitro. Además tiene una capacidad de adsorción a distintas moléculas orgánicas debido a su gran superficie externa y carga tetraédrica que hace que interaccione con sustancias polares como el agua y toxinas. El otro propósito de esta contribución especial, es reconocer la coexistencia de la "Medicina Tradicional" y la "Medicina Occidental", situación que conlleva a la necesidad de la investigación preclínica de diversos recursos naturales.

The inhabitants of the peruvian-bolivian plateau consume a natural substance known as "Chaco", widespread since pre-Columbian era and appreciated for its digestive properties. The Chaco is an edible medicinal clay that is used as slurry with water to restrain dyspeptic discomfort or acid-peptic manifestations. In this contribution we present physicochemical aspects of the composition of the Chaco, experimental animal studies that evaluate its antiulcer effect and in vitro test that studies the antacid property. The proposed mechanism of therapeutic action is due to a cytoprotective effect on the gastric mucosa by independent mechanisms of acid secretion inhibition, as it has no antacid property in vitro. Also it has an adsorptivity to different organic molecules due to their large surface area and tetrahedral charge that makes it to interact with polar substances such as water and toxins. The other purpose of this special contribution is to recognize the coexistence of "Traditional Medicine" and "Western Medicine", a situation which leads to the need for preclinical research of various natural resources.

Alteraciones hematológicas en la diabetes mellitus / Blood disorders in diabetes mellitus

Although it has been treated in a limited way the relationship between diabetes and hematopoietic system, there is evidence demonstrating thedeleterious effect of hyperglycemia on the three cell lines: red blood cells, white cells and platelets. Different forms of anemia associated with hyperglycemia are analyzed and erythrocyte alterations observed in diabetes. In chronic decompensated patients have been demonstrated alterationsof monocytes, lymphocytes and polymorphonuclear particularly, with decreased chemotaxis, adherence, phagocytosis and opsonization. Hyperglycemia determines a prothrombotic state by platelet hyperreactivity, which is a marker of inflammation...

Early postoperative changes in hematological, erythrocyte aggregation and blood coagulation parameters after unilateral implantation of polytetrafluoroethylene vascular graft in the femoral artery of beagle dogs

PURPOSE: The failure of small-caliber vascular grafts still means a serious problem. Concerning the early postoperative complications we aimed to investigate the hemostaseological and hemorheological aspects of this issue in a canine model. METHODS: In the Control group only anesthesia was induced. In the Grafted group under general anesthesia a 3.5-cm segment was resected unilaterally from the femoral artery and replaced with a PTFE graft (diameter: 3 mm). On the 1st-3rd-5th-7th and 14th postoperative days the skin temperature of both hind limbs was measured, and blood sampling occurred for hematological, hemostaseological and hemorheological tests. RESULTS: The skin temperature of the operated versus intact limbs did not differ. In the Grafted group leukocyte count was elevated by the 1st postoperative day, while platelet count increased over the entire follow-up period. Fibrinogen concentration rose on the 1st-5th days, activated partial thromboplastin time increased on the 3rd-7th days. Erythrocyte aggregation was enhanced significantly on the 1st-5th days. In specimens taken on the 14th day, histologically we found matured thrombus narrowing the graft lumen. CONCLUSIONS: Small-caliber PTFE graft implantation into the femoral artery caused significant changes in several hemostaseological and hemorheological parameters. However, better clarifying the factors leading to early thrombosis of these grafts needs further studies. .

Detection of Heparin in the Salivary Gland and Midgut of Aedes togoi

Mosquitoes secrete saliva that contains biological substances, including anticoagulants that counteract a host's hemostatic response and prevent blood clotting during blood feeding. This study aimed to detect heparin, an anticoagulant in Aedes togoi using an immunohistochemical detection method, in the salivary canal, salivary gland, and midgut of male and female mosquitoes. Comparisons showed that female mosquitoes contained higher concentrations of heparin than male mosquitoes. On average, the level of heparin was higher in blood-fed female mosquitoes than in non-blood-fed female mosquitoes. Heparin concentrations were higher in the midgut than in the salivary gland. This indicates presence of heparin in tissues of A. togoi.

Leishmania amazonensis exhibits phosphatidylserine-dependent procoagulant activity, a process that is counteracted by sandfly saliva

Leishmania parasites expose phosphatidylserine (PS) on their surface, a process that has been associated with regulation of host's immune responses. In this study we demonstrate that PS exposure by metacyclic promastigotes of Leishmania amazonensis favours blood coagulation. L. amazonensis accelerates in vitro coagulation of human plasma. In addition, L. amazonensis supports the assembly of the prothrombinase complex, thus promoting thrombin formation. This process was reversed by annexin V which blocks PS binding sites. During blood meal, Lutzomyia longipalpis sandfly inject saliva in the bite site, which has a series of pharmacologically active compounds that inhibit blood coagulation. Since saliva and parasites are co-injected in the host during natural transmission, we evaluated the anticoagulant properties of sandfly saliva in counteracting the procoagulant activity of L. amazonensis . Lu. longipalpis saliva reverses plasma clotting promoted by promastigotes. It also inhibits thrombin formation by the prothrombinase complex assembled either in phosphatidylcholine (PC)/PS vesicles or in L. amazonensis . Sandfly saliva inhibits factor X activation by the intrinsic tenase complex assembled on PC/PS vesicles and blocks factor Xa catalytic activity. Altogether our results show that metacyclic promastigotes of L. amazonensis are procoagulant due to PS exposure. Notably, this effect is efficiently counteracted by sandfly saliva.

Interaction between Paracoccidioides brasiliensis conidia and the coagulation system: involvement of fibrinogen

The infectious process starts with an initial contact between pathogen and host. We have previously demonstrated that Paracoccidioides brasiliensis conidia interact with plasma proteins including fibrinogen, which is considered the major component of the coagulation system. In this study, we evaluated the in vitro capacity of P. brasiliensis conidia to aggregate with plasma proteins and compounds involved in the coagulation system. We assessed the aggregation of P. brasiliensis conidia after incubation with human serum or plasma in the presence or absence of anticoagulants, extracellular matrix (ECM) proteins, metabolic and protein inhibitors, monosaccharides and other compounds. Additionally, prothrombin and partial thromboplastin times were determined after the interaction of P. brasiliensis conidia with human plasma. ECM proteins, monosaccharides and human plasma significantly induced P. brasiliensis conidial aggregation; however, anticoagulants and metabolic and protein inhibitors diminished the aggregation process. The extrinsic coagulation pathway was not affected by the interaction between P. brasiliensis conidia and plasma proteins, while the intrinsic pathway was markedly altered. These results indicate that P. brasiliensis conidia interact with proteins involved in the coagulation system. This interaction may play an important role in the initial inflammatory response, as well as fungal disease progression caused by P. brasiliensis dissemination.

Isolated biomolecules of pharmacological interest in hemostasis from Cerastes cerastes venom

Biomolecules from Cerastes cerastes venom have been purified and characterized. Two phospholipases isolated from Cerastes cerastes venom share 51% of homology. CC2-PLA2 exhibits antiplatelet activity that blocks coagulation. CCSV-MPase, a non-hemorrhagic Zn2+-metalloproteinase, significantly reduced the plasmatic fibrinogen level and hydrolyzes only its Bβ chain. Serine proteinases such as RP34, afaâcytin and CC3-SPase hydrolyze the fibrinogen and are respectively α, αβ and αβ fibrinogenases. In deficient human plasma, afaâcytin replaces the missing factors VIII and IX, and activates purified human factor X into factor Xa. It releases serotonin from platelets and directly aggregates human (but not rabbit) blood platelets. RP34 proteinase also had no effect on both human and rabbit blood platelet aggregation. CC3-SPase revealed a pro-coagulant activity. However, the insolubility of the obtained clot indicates that CC3-SPase does not activate factor XIII. In addition, CC3-SPase clotting activity was carried out with human plasmas from volunteer patients deficient in clotting factors. Results showed that CC3-SPase shortens clotting time of plasma deficient in factors II and VII but with weaker clotting than normal plasma. The clotting time of plasma deficient in factor II is similar to that obtained with normal plasma; suggesting that CC3-SPase is able to replace both factors IIa and VII in the coagulation cascade and thus could be involved in the blood clotting process via an extrinsic pathway. These results imply that CC3-SPase and afaâcytin could repair hemostatic abnormalities and may replace some factors missing in pathological deficiency. Afaâcytin also exhibits α fibrinase property similar to a plasmin-like proteinase. Despite its thrombin-like characteristics, afaâcytin is not inhibited by plasmatic thrombin inhibitors. The procoagulant properties of afaâcytin might have potential clinical applications.

In vivo evaluation of homeostatic effects of Echis carinatus snake venom in Iran

Background: The venom of the family Viperidae, including the saw-scaled viper, is rich in serine proteinases and metalloproteinases, which affect the nervous system, complementary system, blood coagulation, platelet aggregation and blood pressure. One of the most prominent effects of the snake venom of Echis carinatus (Ec) is its coagulation activity, used for killing prey. Materials and methods: Subfractions F1A and F1B were isolated from Ec crude venom by a combination of gel chromatography (Sephadex G-75) and ion exchange chromatography on a DEAE-Sepharose (DE-52). These subfractions were then intravenously (IV) injected into NIH male mice. Blood samples were taken before and after the administration of these subfractions. Times for prothrombin, partial thromboplastin and fibrinogen were recorded. Results and conclusions: Comparison of the prothrombin time before and after F1A and F1B administrations showed that time for blood coagulation after injection is shorter than that of normal blood coagulation and also reduced coagulation time after Ec crude venom injection. This difference in coagulation time shows the intense coagulation activity of these subfractions that significantly increase the coagulation cascade rate and Causes to quick blood coagulation. The LD50 of the Ec crude venom was also determined to be 11.1 µg/mouse. Different crude venom doses were prepared with physiological serum and injected into four mice. Comparison of the prothrombin times after injection of subfractions F1A and F1B showed that the rate of mouse blood coagulation increases considerably. Comparing the partial thromboplastin times after injecting these subfractions with this normal test time showed that the activity rate of intrinsic blood coagulation system rose sharply in mice. Finally, by comparing the fibrinogen time after subfraction injections and normal test time, we can infer intense activation of coagulation cascade and fibrin production.(AU)

Diabetes subdiagnosticado e necrose miocárdica: preditores de hiperglicemia no infarto do miocárdio / Unrecognized diabetes and myocardial necrosis: predictors of hyperglycemia in myocardial infarction

FUNDAMENTO: Hiperglicemia na fase aguda do infarto do miocárdio é importante fator prognóstico. Entretanto, sua fisiopatologia não está completamente elucidada. OBJETIVO: Analisar simultaneamente correlação entre hiperglicemia e marcadores bioquímicos relacionados ao estresse,metabolismo glicídico e lipídico, coagulação, inflamação e necrose miocárdica. MÉTODOS: Oitenta pacientes com infarto agudo do miocárdio foram incluídos prospectivamente. Os parâmetros analisados foram: glicose, hormônios do estresse (cortisol e norepinefrina), fatores do metabolismo glicídico [hemoglobina glicada (HbA1c), insulina], lipoproteínas (colesterol total, LDL, HDL, LDL eletronegativa minimamente modificada e adiponectina), glicerídeos (triglicérides, VLDL e ácido graxo), fatores da coagulação (fator VII, fibrinogênio,inibidor do ativador do plasminogênio-1), inflamação (proteína C reativa ultrassensível) e necrose miocárdica (CK-MB e troponina). Variáveis contínuas foram convertidas em graus de pertinência por intermédio de lógica fuzzy. RESULTADOS: Houve correlação significativa entre hiperglicemia e metabolismo glicídico (p < 0,001), lipoproteínas (p = 0,03) e fatores de necrose (p = 0,03). Na análise multivariada, somente metabolismo glicídico (OR = 4,3; IC = 2,1-68,9 e p < 0,001) e necrose miocárdica (OR = 22,5; IC = 2-253 e p = 0,012) mantiveram correlação independente e significativa.Para análise da influência da história de diabetes mellitus , modelo de regressão, incluindo somente pacientes sem diabetes mellitus foi desenvolvido, e os resultados não alteraram. Finalmente, no modelo ajustado para idade, sexo e variáveis clínicas(história de diabetes mellitus, hipertensão arterial e dislipidemia), três variáveis mantiveram associação significativa e independente com hiperglicemia: metabolismo glicídico (OR = 24,1; IC = 4,8-122,1 e p < 0,001) necrose miocárdica (OR = 21,9; IC = 1,3-360,9 e p = 0,03) e história de DM (OR = 27, IC = 3,7-195,7 e p = 0,001). CONCLUSÃO: Marcadores do metabolismo glicídico e necrose miocárdica foram os melhores preditores de hiperglicemia em pacientes com infarto agudo do miocárdio.

BACKGROUND: Hyperglycemia in the acute phase of myocardial infarction is an important prognostic factor. However, its pathophysiology is not fully understood. OBJECTIVE: To analyze simultaneously the correlation between hyperglycemia and biochemical markers related to stress, glucose and lipid metabolism, coagulation, inflammation, and myocardial necrosis. METHODS Eighty patients with acute myocardial infarction were prospectively included. The following parameters were analyzed: blood glucose; stress hormones (cortisol and norepinephrine); glucose metabolism factors [glycated hemoglobin (HbA1c); insulin]; lipoproteins (total cholesterol, LDL, HDL, minimally modified electronegative LDL, and adiponectin); glycerides (triglycerides, VLDL and fatty acids); coagulation factors (factor VII, fibrinogen, plasminogen activator inhibitor-1); inflammation (high-sensitivity C reactive protein); and myocardial necrosis (CK-MB and troponin). Continuous variables were converted into degrees of relevance using fuzzy logic. RESULTS: Significant correlation was observed between hyperglycemia and glucose metabolism (p < 0.001), lipoproteins (p = 0.03), and necrosis factors (p = 0.03). In the multivariate analysis, only glucose metabolism (OR = 4.3; CI = 2.1-68.9; and p < 0.001) and myocardial necrosis (OR = 22.5; CI = 2-253; and p = 0.012) showed independent and significant correlation. For the analysis of the influence of history of diabetes mellitus, a regression model including only patients without diabetes mellitus was developed, and the results did not change. Finally, in the model adjusted for age, gender, and clinical variables (history of diabetes mellitus, hypertension and dyslipidemia), three variables maintained a significant and independent association with hyperglycemia: glucose metabolism (OR = 24.1; CI = 4.8-122.1; and p < 0.001), myocardial necrosis (OR = 21.9; CI = 1.3-360.9; and p = 0.03), and history of DM (OR = 27; CI = 3.7-195.7; and p = 0.001). CONCLUSION: Glucose metabolism and myocardial necrosis markers were the best predictors of hyperglycemia in patients with acute myocardial infarction.

Decreased plasma ADAMTS-13 activity as a predictor of postoperative bleeding in cyanotic congenital heart disease

OBJECTIVE: To analyze the preoperative plasma antigenic concentration and activity of von Willebrand factor and its main cleaving protease ADAMTS-13 in pediatric patients with cyanotic congenital heart disease undergoing surgical treatment and investigate possible correlations with postoperative bleeding. METHODS: Plasma antigenic concentrations (von Willebrand factor:Ag and ADAMTS-13:Ag) were measured using enzyme-linked immunoassays. Collagen-binding assays were developed to measure biological activities (von Willebrand factor:collagen binding and ADAMTS-13 activity). The multimeric structure of von Willebrand factor was analyzed using Western immunoblotting. Demographic, diagnostic, and general and specific laboratory data and surgery-related variables were subjected to univariate, bivariate, and multivariate analysis for the prediction of postoperative bleeding. RESULTS: Forty-eight patients were enrolled, with ages ranging from 9 months to 7.6 years (median 2.5 years). The plasma concentrations of von Willebrand factor:Ag and ADAMTS-13:Ag were decreased by 65 and 82%, respectively, in the patients compared with the controls (p<0.001). An increased density of low-molecular-weight fractions of von Willebrand factor, which are suggestive of proteolytic degradation (p = 0.0081), was associated with decreased ADAMTS-13 activity, which was likely due to ADAMTS-13 consumption (71% of controls, p = 0.0029) and decreased von Willebrand factor:collagen binding (76% of controls, p = 0.0004). Significant postoperative bleeding occurred in 13 patients. The preoperative ADAMTS-13 activity of <64.6% (mean level for the group), preoperative activated partial thromboplastin time, and the need for cardiopulmonary bypass were characterized as independent risk factors for postoperative bleeding, with respective hazard ratios of 22.35 (95% CI 1.69 to 294.79), 1.096 (95% CI 1.016 to 1.183), and 37.43 (95% ...