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.

El juicio clínico: clave en la selección ante "el variado menú" de pruebas de laboratorio en hemostasia / Clinical judgment: key in the selection within the "diverse list" of laboratory tests in hemostasis

Los trastornos de la coagulación manifiestos con hemorragia, han sido una preocupación natural para el hombre a través del tiempo, quien instintivamente ve en el sangrado un signo de alarma que evoca una situación de enfermedad grave, e incluso que anticipa la muerte [1]. Paralelamente, la medicina se ha mostrado interesada en entender los fenómenos hemostáticos en busca de clasificar y tratar las condiciones de hemorragia (coagulopatía) y de trombosis (trombofilia). Así, los avances desde finales del siglo XIX a la fecha, nos han llevado a dilucidar un sistema de coagulación muy complejo [2], que se relaciona de formas diversas con otras funciones fisiológicas como la respuesta inmune, los procesos de reparación tisular y la reproducción. Es positivo que el laboratorio clínico especializado en hemostasia se vaya equipando con pruebas con enfoque tanto cualitativo como cuantitativo para la evaluación de la hemostasia. Algunas de estas dan una visión general (con limitaciones) de la coagulación, y otras son tan precisas que dan cuenta del reemplazo de incluso un solo nucleótido en extensas secuencias de genes de proteínas relacionadas con este sistema. Paradójicamente, cuando tenemos tantas pruebas para analizar diversas variables de un fenómeno complejo y dinámico, nos enfrentamos a un reto de selección como clínicos, en el cual debemos hacer el mayor esfuerzo por elegir pruebas de alto valor diagnóstico, evitando los falsos positivos, falsos negativos o peor aún, la irrelevancia y futilidad de exámenes que demandan una logística y costo importantes

Diagnóstico de la enfermedad de von Willebrand / Diagnosis of von Willebrand disease

La enfermedad de von Willebrand (EVW) es el trastorno hemorrágico hereditario más común, y se caracteriza por presentar disminución de la capacidad del factor von Willebrand (FVW) de unirse a las plaquetas y al colágeno de la matriz extracelular durante la hemostasia primaria, debido a defectos cuantitativos o cualitativos. La EVW se clasifica en tres fenotipos principales: el 1 y el 3 que son trastornos cuantitativos, y el 2 que se subclasifica en 2A, 2B, 2M y 2N, y refleja los trastornos cualitativos. Para su diagnóstico son necesarios varios pasos: 1) la evaluación del historial de sangrado personal y familiar del paciente, 2) detección inicial de trastornos hemorrágicos, 3) pruebas para la detección de la EVW, 4) pruebas para la tipificación de la EVW, y 5) el análisis molecular. Tanto la subclasificación de la EVW como su diagnóstico continúan planteando desafíos importantes, motivo por el cual se realiza esta revisión, de manera que los profesionales de la salud tengan una guía que los oriente al momento de tener pacientes con algún trastorno hemorrágico que amerite descartar una EVW e implementar un tratamiento adecuado

von Willebrand disease (VWD) is the most common hereditary bleeding disorder, and is characterized by a decreased ability of the von Willebrand factor (VWF) to bind to platelets and extracellular matrix collagen during primary hemostasis, due to quantitative or qualitative defects. VWD is classified into three main phenotypes: 1 and 3, which are quantitative disorders, and 2 (2A, 2B, 2M and 2N) that reflects qualitative disorders. Several steps are necessary for its diagnosis: 1) evaluation of the patient's personal and family bleeding history, 2) initial screening tests for bleeding disorders, 3) tests for the detection of VWD, 4) tests for the classification of VWD, and 5) molecular analysis. Both the subclassification of VWD and its diagnosis continue to represent important challenges, which we aimed to describe in this review, so that health professionals have a guide to assist them when they have patients with a bleeding disorder that requires exclusion of VWD, and implementation of an appropriate treatment.

Antígeno del factor von Willebrand (FVW: Ag) / von Willebrand factor antigen (VWF: Ag)

Utilidad clínica de la prueba El factor von Willebrand (FVW) es una glicoproteína compuesta por multímeros con pesos moleculares que pueden variar desde 500 KDa hasta 20.000 kDa, que se sintetiza en las células endoteliales y en los megacariocitos, y se almacena en los cuerpos de Weibel-Palade y en los gránulos alfa de las plaquetas [1]. El papel del FVW en la hemostasia primaria es mediar la adhesión de las plaquetas a los componentes de la matriz extracelular, a través de los complejos glucoproteicos plaquetarios GPIbα y αIIb3ß; en la hemostasia secundaria, se asocia con el factor VIII para prevenir su degradación y favorecer la generación de trombina para la formación del trombo final

Manejo del paciente anticoagulado en una cirugía dental / Management of the anticoagulated patient in dental surgery / Gerenciamento do paciente anticoagulado em cirurgia odontológica

Introducción: una adecuada hemostasia es crucial para el éxito del tratamiento odontológico invasivo, ya que los problemas de sangrado pueden dar lugar a complicaciones asociadas a una importante morbimortalidad. El tratamiento odontológico de pacientes que tienden a un mayor riesgo de sangrado debido al uso de fármacos anticoagulantes plantea un desafío en la práctica diaria de los profesionales de la odontología. El conocimiento adecuado de los mecanismos subyacentes a la hemostasia y el manejo optimizado de estos pacientes son, por lo tanto, cuestiones muy importantes. Se realiza un estudio de los fármacos anticoagulantes actualmente disponibles en el mercado, evaluando los riesgos y beneficios de suspender dicho fármaco previo a un tratamiento odontológico invasivo. Además, se hace una revisión de los protocolos de manejo actuales que se utilizan en estos pacientes. Material y métodos: se realizó una búsqueda bibliográfica en las bases de datos Epistemonikos y Medline/PubMed; en el portal Timbó y en la biblioteca virtual Scielo. Abarcando todos los estudios publicados en los últimos 15 años en inglés y español. Se encontraron 30 artículos, se seleccionaron 15 en primera instancia para finalizar con 11 artículos. En dicha selección el filtro fue que los demás artículos se referían a otros anticoagulantes que no eran parte de este trabajo. Resultados: se han desarrollado múltiples protocolos de manejo, aunque en todos los casos se requiere una historia clínica completa, junto con pruebas hemostáticas complementarias para minimizar los riesgos derivados del tratamiento odontológico. Discusión: muchos autores consideran que la medicación de los pacientes indicada para el tratamiento de una enfermedad de base no debe ser alterada o suspendida a menos que así lo indique el médico prescriptor. Se ha demostrado que las medidas hemostáticas locales son suficientes para controlar los posibles problemas de sangrado derivados del tratamiento dental.

Introduction: Adequate hemostasis is crucial for the success of invasive dental treatment, since bleeding problems can lead to complications associated with significant morbidity and mortality. The dental treatment of patients who are prone to an increased risk of bleeding due to the use of anticoagulant drugs poses a challenge in the daily practice of dental professionals. Adequate knowledge of the mechanisms underlying hemostasis and optimized management of these patients are therefore very important issues. A review is made of the anticoagulant drugs currently available on the market, evaluating the risks and benefits of suspending such a drug prior to invasive dental treatment. In addition, a review is made of the current management protocols used in these patients. Material and methods: A bibliographic search was carried out in the Epistemonikos and Medline/PubMed databases; in the Timbo portal and in the Scielo virtual library. All the studies published in the last 15 years in English and Spanish were included. Thirty articles were found, 15 were selected in the first instance to end up with 11 articles. In this selection, the filter was that the other articles referred to other anticoagulants that were not part of this work. Results: multiple management protocols have been developed, although in all cases a complete clinical history is required, together with complementary hemostatic tests to minimize the risks derived from dental treatment. Discussion: many authors consider that the patient's medication indicated for the treatment of an underlying disease should not be altered or suspended unless so indicated by the prescribing physician. It has been shown that local hemostatic measures are sufficient to control possible bleeding problems derived from dental treatment.

Introdução: A hemostasia adequada é crucial para o sucesso do tratamento dentário invasivo, pois problemas de sangramento podem levar a complicações associadas a uma morbidade e mortalidade significativas. O tratamento odontológico de pacientes que são propensos a um risco maior de sangramento devido ao uso de drogas anticoagulantes representa um desafio na prática diária dos profissionais da odontologia. O conhecimento adequado dos mecanismos subjacentes à hemostasia e o gerenciamento otimizado desses pacientes são, portanto, questões muito importantes. É realizada uma revisão dos anticoagulantes atualmente disponíveis no mercado, avaliando os riscos e benefícios de descontinuar tal medicamento antes do tratamento dentário invasivo. Além disso, é feita uma revisão dos protocolos de gerenciamento atuais usados nesses pacientes. Material e métodos: Foi realizada uma pesquisa bibliográfica nas bases de dados Epistemonikos e Medline/PubMed; no portal Timbo e na biblioteca virtual Scielo. Todos os estudos publicados nos últimos 15 anos, em inglês e espanhol, foram incluídos. Trinta artigos foram encontrados, 15 foram selecionados em primeira instância para acabar com 11 artigos. Nesta seleção, o filtro foi que os outros artigos se referiam a outros anticoagulantes que não faziam parte deste trabalho. Resultados: foram desenvolvidos múltiplos protocolos de gerenciamento, embora em todos os casos seja necessário um histórico clínico completo, juntamente com testes hemostáticos complementares para minimizar os riscos derivados do tratamento odontológico. Discussão: muitos autores consideram que a medicação os pacientes indicada para o tratamento de uma doença subjacente não deve ser alterada ou descontinuada, a menos que o médico que a prescreve dê instruções nesse sentido. Medidas hemostáticas locais demonstraram ser suficientes para controlar potenciais problemas de sangramento resultantes do tratamento odontológico.

Achyrocline satureioides (Lam) DC extracts acting as enzyme modulators: digestion, inflammation, and hemostasis / Extratos de Achyrocline satureioides (Lam) DC atuando como moduladores enzimáticos: digestão, inflamação e hemostasia

Achyrocline satureioides is popularly known for its richness in phenolic compounds and medicinal properties (anti-inflammatory, analgesic, and hepatoprotective). The present study aimed at broadening the knowledge about the pharmacological potential exerted by the aqueous and ethanolic extracts of A. satureioides. These extracts were characterized by HPLC and tested for their modulatory action on phospholipases A2 and proteases of snake venoms. In addition, they were tested on the activities of digestive enzymes. Snake venoms were used as tools since they have enzymes with high functional and structural homology to human enzymes. The results demonstrate that the extracts of A. satureioides act as enzymatic inhibitors or potentiators, interfering in processes related to the hemostasis, such as coagulation and thrombus dissolution. In addition, the anti-genotoxic activity and inhibitions exerted on digestive enzymes suggests their potential use in the prevention and/or treatment of several pathologies. New studies could provide information on how the compounds present in the extracts and the different enzymes interact.

A Achyrocline satureioides é popularmente conhecida por sua riqueza em compostos fenólicos e por suas propriedades medicinais (anti-inflamatória, analgésica e hepatoprotetora). No presente estudo, com o objetivo de ampliar o conhecimento sobre o potencial farmacológico exercido por esses extratos, os extratos aquoso e etanólico de A. satureioides foram caracterizados por HPLC e testados quanto à sua ação modulatória sobre as fosfolipases A2 e proteases de peçonhas de serpentes. Além disso, também foram testados em atividades de enzimas digestivas. As peçonhas de serpentes foram usadas como ferramentas por apresentarem enzimas com alta homologia funcional e estrutural às humanas. Os resultados demonstram que os extratos de A. satureioides atuam como inibidores ou potencializadores enzimáticos, interferindo em processos relacionados à hemostasia, como coagulação e dissolução do trombo. Além do mais, destacam seu potencial antigenotóxico e as inibições exercidas sobre as enzimas digestivas direcionando seu potencial de uso na prevenção e/ou tratamento de diversas patologias. Novos estudos poderão fornecer informações sobre os mecanismos de interação entre os compostos presentes nos extratos e as diferentes enzimas.

Thrombolysis, clotting, and genotoxic activities modulated by essential oils extracted from Lippia alba

Abstract The composition and pharmacological properties of Lippia alba (Mill.) (L. alba) (Verbenaceae) flower and leaf essential oils (EO) were determined in this study. The major constituents in the flower EO were geranial (49.83%) and neral (32.75%), and in the leaf EO were geranial (38.06%), neral (31.02%), and limonene (18.03%). Flower EO inhibited thrombolysis induced by Bothrops moojeni (B. moojeni) and Lachesis muta muta (L. muta muta) venoms (0.05-1.2 µL mL-1). When tested against L. muta muta venom, the protective effect was smaller in both EO. The EOs prolonged the clotting time induced by L. muta muta venom and a procoagulant effect was observed on B. moojeni. In the comet assay, the flower EO presented anti-genotoxic action (damage frequency of only 11.6 - 34.9%) against the L. muta muta venom. The positive control (Doxorubicin) and the venom alone presented a damage frequency of 80.3% and 70.7%, respectively. The flower EO protected DNA from damage induced by L. muta muta venom. L. alba leaf and flower EOs presented anti-genotoxic action

Immediate postoperative color Doppler ultrasonography on the diagnosis of hemorrhagic complications of liver biopsy and its directed compression hemostasis / 中华肝脏病杂志

Objective: To study the diagnostic value of immediate color Doppler ultrasonography on traumatic hepatic hemorrhage after tissue sampling with ultrasound-guided liver biopsy and the clinical effect of its-directed local compression hemostasis at puncture-site. Methods: 132 hospitalized patients with various liver diseases underwent ultrasound-guided hepatic puncture-biopsies, including 61 cases with diffuse parenchymal and 71 cases with focal liver lesions. Immediate postoperative color Doppler ultrasonography was performed following liver biopsy. Abnormal blood flow signal was observed at hepatic puncture biopsy site, and if there were hemorrhagic signals, ultrasound-directed local compression hemostasis was performed until the bleeding signal disappeared. F-test and Chi-square test were used for statistical analysis. Results: Immediate color Doppler ultrasonography showed traumatic hemorrhage in 36.1% (22/61) and 40.8% (29/71) cases of diffuse liver disease and focal liver disease group, respectively. All hemorrhagic signals were eventually disappeared after ultrasound-directed local compression hemostasis. The median hemostasis time was 2 min in both groups, and there was no statistically significant difference in bleeding rate and hemostasis time between the two groups (P>0.05). There were no serious complications and deaths. Conclusion: Traumatic hepatic hemorrhage along the needle puncture tract is a common accompanying condition during liver biopsy. Immediate postoperative color Doppler ultrasonography can trace bleeding signals in timely manner and direct effective compression hemostasis, so it should be used routinely to help avoid occurrence of severe hemorrhagic complications.

Application and Prospect of Platelet Multi-Omics Technology in Study of Blood Stasis Syndrome / 中国结合医学杂志

The abnormality of platelet function plays an important role in the pathogenesis and evolution of blood stasis syndrome (BSS). The explanation of its mechanism is a key scientific issue in the study of cardiovascular and cerebrovascular diseases and treatment. System biology technology provides a good technical platform for further development of platelet multi-omics, which is conducive to the scientific interpretation of the biological mechanism of BSS. The article summarized the pathogenesis of platelets in BSS, the mechanism of action of blood activating and stasis resolving drugs, and the application of genomics, proteomics, and metabonomics in platelet research, and put forward the concept of "plateletomics in BSS". Through the combination and cross-validation of multi-omics technology, it mainly focuses on the clinical and basic research of cardiovascular and cerebrovascular diseases; through the interactive verification of multi-omics technology and system biology, it mainly focuses on the platelet function and secretion system. The article systematically explains the molecular biological mechanism of platelet activation, aggregation, release, and other stages in the formation and development of BSS, and provides a new research idea and method for clarifying the pathogenesis of BSS and the mechanism of action of blood activating and stasis resolving drugs.

Absorbable Hemostatic Material with High Water Absorption Based on Polysaccharide / 中国医疗器械杂志

An absorbable hemostatic material based on polysaccharide was prepared. The concentration of blood cells and coagulation factors was increased by reducing the water content in the blood, so as to reduce the coagulation time and achieve the purpose of rapid hemostasis. The specific surface area of starch was increased by using hydrochloric acid to hydrolyze potato starch, which made it easier to combine with α-amylase and increased the degradation rate. Starch was crosslinked into microspheres by crosslinking agent, which made the particle size uniform and greatly improved the water absorption. The surface modification of crosslinked starch microspheres with carboxymethyl group can further improve the water absorption of hemostatic materials. The results showed that the water absorption rate of our hemostatic material was more than 800%, and the average hemostatic time in the animal model was 138.7s. Compared with the imported products on the market, our hemostatic material have better hemostatic performance.

Trauma-induced coagulopathy: Mechanisms and clinical management

INTRODUCTION@#Trauma-induced coagulopathy (TIC) is a form of coagulopathy unique to trauma patients and is associated with increased mortality. The complexity and incomplete understanding of TIC have resulted in controversies regarding optimum management. This review aims to summarise the pathophysiology of TIC and appraise established and emerging advances in the management of TIC.@*METHODS@#This narrative review is based on a literature search (MEDLINE database) completed in October 2020. Search terms used were "trauma induced coagulopathy", "coagulopathy of trauma", "trauma induced coagulopathy pathophysiology", "massive transfusion trauma induced coagulopathy", "viscoelastic assay trauma induced coagulopathy", "goal directed trauma induced coagulopathy and "fibrinogen trauma induced coagulopathy'.@*RESULTS@#TIC is not a uniform phenotype but a spectrum ranging from thrombotic to bleeding phenotypes. Evidence for the management of TIC with tranexamic acid, massive transfusion protocols, viscoelastic haemostatic assays (VHAs), and coagulation factor and fibrinogen concentrates were evaluated. Although most trauma centres utilise fixed-ratio massive transfusion protocols, the "ideal" transfusion ratio of blood to blood products is still debated. While more centres are using VHAs to guide blood product replacement, there is no agreed VHA-based transfusion strategy. The use of VHA to quantify the functional contributions of individual components of coagulation may permit targeted treatment of TIC but remains controversial.@*CONCLUSION@#A greater understanding of TIC, advances in point-of-care coagulation testing, and availability of coagulation factors and fibrinogen concentrates allows clinicians to employ a more goal-directed approach. Still, hospitals need to tailor their approaches according to available resources, provide training and establish local guidelines.

Detection of Hemostasis Abnormalities in Type 2 Diabetes Mellitus Using Thromboelastography / Journal of the ASEAN Federation of Endocrine Societies

Introduction@#Type 2 DM (T2DM) is associated with inflammation and vascular dysfunction which impact hemostasis. Thromboelastography (TEG) as a hemostasis assessment method, is not routinely applied in T2DM.@*Methodology@#A cross-sectional study was conducted among T2DM patients attending the Endocrinology Clinic of Saiful Anwar Hospital, Indonesia. Glycemic profiles were determined using fasting plasma glucose (FPG), 2-hour postprandial plasma glucose (2hPPG), and glycosylated hemoglobin (HbA1c). Therapy for T2DM was classified into insulin and non-insulin regimens. The primary and secondary hemostasis profile were examined using TEG and was classified as hypo- hyper- and normo-coagulable states.@*Result@#A total of 57 T2DM patients were included. Kruskal-Wallis test did not reveal a significant association between glycemic profiles and groups of hemostasis. However, the median HbA1c was higher in the hypercoagulable group of primary hemostasis and fibrinolysis. The median FPG and 2hPPG were higher in the normo-coagulable group of secondary hemostasis. Logistic regression did not indicate a significant association between type of therapy for diabetes and hemostasis profile.@*Conclusion@#This study did not find significant associations between glycemic levels and type of DM therapy with hemostasis profiles using the TEG method in patients with T2DM.

A Novel Lyophilized PRP-Loaded Gel Based on Chitosan and PEG with Hemostatic and Antibacterial Properties / 中国实验血液学杂志

OBJECTIVE@#A dynamic gel loaded with lyophilized platelet-rich plasma-chitosan/difunctionalized polyethylene glycol (LPRP-CP) was prepared to investigate its hemostatic antibacterial and promoting wound healing of scald wounds through in vitro and in vivo experiments.@*METHODS@#In this study, normal gauze/blank tablet (Ctrl), LPRP-CP, Chitosan HUCHUANG Powder(Chito P)and ChitoGauze XP PRO group (Chito G group) were set. The hemostatic effect and promoting healing effect of the four groups of materials were evaluated by establishing rabbit ear artery hemorrhage model and superficial Ⅱ° scalded model of skin on the back. The hemostatic time and bleeding amount were calculated and the gross and histological results of scald healing were observed. The antibacterial effect of the four groups of materials was evaluated by antibacterial test in vitro.@*RESULTS@#In the rabbit ear arterial hemorrhage model, the hemostasis of all materials was successful. The hemostatic time of Ctrl, Chito P, LPRP-CP and Chito G groups was 213.33±38.30, 118.33±24.01, 115.00±8.37 and 111.67±11.69 s, respectively. The blood loss was 1233.83±992.27, 346.67±176.00, 193.33±121.47 and 147.50±80.66 mg, respectively. Compared with Ctrl, the hemostasis time of LPRP-CP, Chito P and Chito G group was significantly shorter (P<0.001), and the amount of blood loss of LPRP-CP and Chito G group was decreased (P<0.05). Compared with LPRP-CP, there were no significant differences in hemostatic time and blood loss between Chito P and Chito G group (P>0.05). In the model of superficial Ⅱ° scalded on the back of rabbit, the wound healing rate of LPRP-CP was faster than that of the other three groups at the same time, and the healing effect was perfect. In the antibacterial test in vitro, only LPRP-CP had better anti-S. aureus effect, and all groups had no anti-E. coli effect.@*CONCLUSION@#LPRP-CP is an excellent hemostatic material for superficial wounds, and has certain antibacterial and wound healing effects, which has a wide academic value and research prospects.

Sangre total leucorreducida y filtro ahorrador de plaquetas preserva su función hemostática por 21 días: ¿La resucitación hemostática podría ser una realidad en Colombia? / Leukoreduced whole blood and platelet-sparing filter preserves its hemostatic function for 21 days: Could hemostatic resuscitation become a reality in Colombia?

Introducción. La resucitación hemostática es una estrategia para compensar la pérdida sanguínea y disminuir el impacto de la coagulación inducida por trauma. Debido a que la disponibilidad de transfundir una razón equilibrada de hemocomponentes es difícil de lograr en el entorno clínico, la sangre total ha reaparecido como una estrategia fisiológica, con ventajas logísticas, que le permiten ser accesible para iniciar tempranamente la resucitación hemostática. El objetivo de este estudio fue evaluar las propiedades celulares, coagulantes y viscoelásticas de la sangre total almacenada por 21 días. Métodos. Las unidades de sangre total fueron obtenidas de 20 donantes voluntarios sanos. Se procesaron mediante un sistema de leucorreducción ahorrador de plaquetas y fueron almacenadas en refrigeración (1-6°C) sin agitación. Se analizaron los días 0, 6, 11 y 21. Las bolsas fueron analizadas para evaluar las líneas celulares, niveles de factores de coagulación y propiedades viscoelásticas mediante tromboelastografía. Resultados. El conteo eritrocitario y la hemoglobina se mantuvieron estables. El conteo de plaquetas tuvo una reducción del 50 % al sexto día, pero se mantuvo estable el resto del seguimiento. Los factores de coagulación II-V-VII-X, fibrinógeno y proteína C se mantuvieron dentro del rango normal. La tromboelastografía mostró una prolongación en el tiempo del inicio de la formación del coágulo, pero sin alterar la formación final de un coágulo estable. Conclusiones. La sangre total leucorreducida y con filtro ahorrador de plaquetas conserva sus propiedades hemostáticas por 21 días. Este es el primer paso en Colombia para la evaluación clínica de esta opción, que permita hacer una realidad universal la resucitación hemostática del paciente con trauma severo.

Background. Hemostatic resuscitation is a strategy to compensate blood loss and reduce the impact of trauma-induced coagulopathy. However, balanced resuscitation presents challenges in its application in the clinical setting. Whole blood has re-emerged as a physiologic strategy with logistical advantages that offer the opportunity for early initiation of hemostatic resuscitation. The study aims to evaluate the cellular, coagulation, and viscoelastic properties of whole blood preserved for 21 days. Methods. Whole blood units were donated by 20 healthy volunteers. These units were processed using a platelet-sparing leukoreduction filtration system. Units were stored under refrigeration (1-6°C) without agitation and were sampled on days 0, 6, 11, 16, and 21. The units were tested to assess its cellular properties and coagulation factors levels. In addition, viscoelastic features were tested using tromboelastography.Results. Red blood cells count and hemoglobin levels remained stables. Platelet count had a 50% reduction on day 6, and then remained stable for 21 days. Factors II-V-VII-X, fibrinogen, and protein C remained within normal range. Tromboelastrography test showed that the reaction time of clot formation is prolonged, but the final clot formation is not altered. Conclusion. Whole blood retains its hemostatic properties for 21 days. This is the first step to evaluate the use of whole blood in the resuscitation protocols for Colombia allowing hemostatic resuscitation become a universal reality.

Trastornos de la coagulación en cirrosis hepática: artículo de revisión / Coagulation disorders in liver cirrhosis: a review article

Los eventos fisiopatológicos de la cirrosis hepática alteran drásticamente los procesos de hemostasia primaria, secundaria y fibrinólisis. Antiguamente se conceptuaba que dichas alteraciones predisponían exclusivamente a un estado de hipocoagulabilidad, debido a la baja producción hepática de factores procoagulantes y a la trombocitopenia característica. Actualmente existe evidencia de mecanismos de compensación que llevan a un reequilibrio hemostático, que es inestable y fácilmente desregulado ante comorbilidades, complicaciones y progresión de la enfermedad, conduciendo a fenómenos prohemorrágicos o protrombóticos, como trombosis venosa portal, tromboembolismo venoso, etc. Para determinar eficazmente si un paciente cirrótico tiene riesgo de sangrado, no son de utilidad las pruebas de coagulación convencionales. El tratamiento dependerá del estado hipo o hipercoagulable del paciente. Para ello desarrollamos una revisión de los fenómenos hemostáticos en la cirrosis, con el fin de dar a conocer sus características, el método de diagnóstico más eficaz y los tratamientos disponibles.

The pathophysiological events of liver cirrhosis drastically alter the processes of primary and secondary hemostasis and fibrinolysis. Previously, it was conceptualized that these alterations exclusively predisposed to hypocoagulation, due to the low hepatic production of procoagulant factors and the characteristic thrombocytopenia. Currently, there is evidence of compensation mechanisms that lead to a hemostatic rebalancing, which is unstable and easily dysregulated in the presence of comorbidities, complications and progression of the disease, leading to prohemorrhagic or prothrombotic phenomena, such as portal vein thrombosis, venous thromboembolism, etc. To effectively determine whether a cirrhotic patient is at risk for bleeding, conventional coagulation tests are not helpful. Treatment will depend on the hypo or hypercoagulable state of the patient. In this manuscript, we review the hemostatic phenomena in cirrhosis, to reveal its characteristics, effective diagnostic methods and treatment.

Prevalence and outcomes of thrombotic and hemorrhagic complications in pediatric acute promyelocytic leukemia in a tertiary Brazilian center

Abstract Introduction: Little attention is given to thrombosis associated with pediatric acute promyelocytic leukemia (APL). This study describes the thrombotic and hemorrhagic manifestations of APL in pediatric patients and evaluates their hemostasis, based on coagulation tests. Methods: Inclusion criteria were age 0-18 years and APL diagnosis between April 2005 and November 2017. Patients who had received blood transfusion prior to coagulation tests were excluded. Baseline coagulation tests, hematologic counts, and hemorrhagic/thrombotic manifestations were evaluated. Results: Median age was 10.7 years (1-15 years). The initial coagulation tests revealed a median Hgb of 8.3 g/dL (4.7-12.9 g/dL), median leucocyte count of 10.9 × 109/L (1.1-95.8 × 109/L), median platelet count of 31.8 × 109/L (2.0-109.0 × 109/L), median activated partial thromboplastin time (aPTT) of 31.7 s (23.0-50.4 s), median aPTT ratio of 1.0 (0.78-1.6), median thromboplastin time (PT) of 17.5 s (13.8-27.7 s), median PT activity of 62% (25-95 %), and median fibrinogen of 157.7 mg/dL (60.0-281.0 mg/dL). Three patients (13%) had thrombosis. At diagnosis, 21 patients (91.3%) had bruising, one patient (4.3%) had splenic vein and artery thrombosis and one patient (4.3%) presented without thrombohemorrhagic manifestations. During treatment, two patients (8.6%) had thrombosis. Conclusion: Knowledge of thrombosis in pediatric APL is important to determine its risk factors and the best way to treat and prevent this complication.

An evaluation of the relationship between vitamin D level and CTRP-9, tumor necrosis factor-alpha, thiol-disulfide hemostasis in women

SUMMARY OBJECTIVE: Many chronic diseases such as malignancy, cardiovascular diseases, endothelial dysfunction, and autoimmune diseases, which have been shown to be related to vitamin D in various studies; have similar relations with CTRP-9, TNFα, and thiol-disulfide hemostasis. We aimed to contribute to the literature by evaluating the relationship between CTRP-9, TNFα, and thiol-disulfide hemostasis and vitamin D levels, which we thought may have some effects on the pathogenesis of vitamin D deficiency. METHODS: In our study, 78 female volunteers older than 18 years were included. Volunteers were divided into three groups according to the reference values of vitamin D levels. Biochemical parameters, CTRP-9, TNFα, and thiol/disulfide hemostasis tests taken from all volunteers were studied. RESULTS: In this study, there was a significant difference in CTRP-9, TNFα, total thiol (TT), native thiol (NT), DIS (disulfide), TT/DIS, and NT/DIS levels in vitamin D groups (p<0.05). There was a significant negative correlation between vitamin D and TNFα and DIS, while a significant positive correlation was found with CTRP-9, TT, NT, TT/DIS, and NT/DIS (p<0.05). CONCLUSIONS: It was determined that vitamin D deficiency causes a significant decrease in CTRP-9 level and a significant increase in TNFα level, as well as an increase in thiol/disulfide hemostasis in favor of disulfide, which may be a risk factor for increased oxidative stress. We considered that these changes may play mediator roles for many chronic diseases and metabolic disorders that are increasing in frequency due to vitamin D deficiency.

Rapid hemostasis: a novel and effective outpatient procedure using microwave ablation to control epistaxis of isolated mucosal bulge lesions / Hemostasia rápida: um procedimento ambulatorial novo e eficaz utilizando ablação por micro-ondas para controlar a epistaxe de lesões isoladas protuberantes da mucosa

Abstract Introduction Recurrent epistaxis is commonly encountered in the rhinology outpatient clinic. Under endoscopic guidance, both bipolar cautery and monopolar forceps (combined with suction) have been employed to control the bleeding. However, the use of monopolar forceps requires the placement of grounding pads. Most procedures are currently performed in operating rooms. Objective We investigated outcomes after the use of Microwave Ablation (MWA) to control epistaxis in adults with isolated mucosal bulge lesions. All procedures were performed with patients under local anesthesia in our outpatient clinic. Methods This is a retrospective cohort study. We included 83 adults with epistaxis of isolated mucosal bulge lesions. Microwave ablation was performed in the outpatient clinic to control bleeding, after induction of local anesthesia. The primary outcome was successful hemostasis. The secondary outcomes were the rebleeding rates at weeks 1 and 4 and month 6, and complications (crust or synechiae formation, septal perforation, and/or orbit or brain complications). Results All bleeding points were successfully ablated; hemostasis was achieved within 1-2 min. The mean pain score was 1.83 intra-operatively and 0.95 1 h postoperatively. No patient re-bled, and no severe MWA-related complication (septal perforation, synechiae formation, or orbit or brain complication) was recorded to 6 months of follow-up. Conclusions Endoscopic microwave ablation with patients under local anesthesia is a novel, safe, effective, rapid, well-tolerated, outpatient treatment for adults with epistaxis of isolated mucosal bulge lesions, especially those for whom general anesthesia might be risky, those with electrical implants, and those exhibiting contraindications for arterial embolization.

Resumo Introdução Epistaxe recorrente é comumente encontrada no ambulatório de rinologia. Sob orientação endoscópica, foram empregados tanto o cautério bipolar quanto a pinça monopolar (combinados à sucção) para controlar a condição. No entanto, o uso de pinças monopolares requer a colocação de placas de aterramento. Atualmente, a maioria dos procedimentos é feita em salas de cirurgia. Objetivo Investigamos os resultados após o uso da ablação por micro-ondas (MWA, do inglês Microwave Ablation) no controle da epistaxe em adultos com lesões isoladas protuberantes da mucosa. Todos os procedimentos foram feitos em nosso ambulatório com os pacientes sob anestesia local. Métodos Estudo de coorte retrospectivo. Foram incluídos 83 adultos com epistaxe de lesões isoladas protuberantes da mucosa. A ablação por micro-ondas foi feita no ambulatório para controlar o sangramento, após a administração de anestesia local. O desfecho primário foi uma hemostasia bem-sucedida. Os desfechos secundários foram as taxas de ressangramento, nas semanas 1 e 4 e no mês 6, e complicações (formação de crostas ou sinéquias, perfuração septal e/ou complicações orbitais ou cerebrais). Resultados Todos os pontos de sangramento foram contidos com sucesso; a hemostasia foi alcançada em 1-2 minutos. O escore médio de dor foi de 1,83 no intraoperatório e de 0,95 1 h no pós-operatório. Nenhum paciente apresentou ressangramento e nenhuma complicação grave relacionada à MWA (perfuração septal, formação de sinéquias ou complicações orbitais ou cerebrais) foi registrada em 6 meses de seguimento. Conclusões A ablação endoscópica por micro-ondas com pacientes sob anestesia local é um tratamento ambulatorial novo, seguro, eficaz, rápido e bem tolerado para adultos com epistaxe de lesões isoladas protuberantes da mucosa, especialmente aqueles para os quais a anestesia geral pode ser arriscada, indivíduos com implantes elétricos e aqueles com contraindicações para embolização arterial.

Trastornos plaquetarios hereditarios poco frecuentes: patología molecular y aspectos diagnósticos / Infrequent hereditary platelets disorders: molecular pathology and diagnostic aspects

Introducción: Las plaquetas tienen una función clave en la hemostasia primaria a través de cuatro mecanismos fundamentales: adhesión, agregación, secreción y actividad procoagulante, todos controlados genéticamente por más de 50 genes asociados que han sido identificados. Las manifestaciones clínicas en las alteraciones hereditarias de las plaquetas suelen ser variables; aunque estas alteraciones de la coagulación suelen presentarse con una trombocitopenia notoria, también pueden exhibir trombocitopatías, en las cuales la capacidad hemostática de las plaquetas resulta afectada sin variar su número. Por tanto, existen gran variedad de manifestaciones fenotípicas y mutaciones en relación con la función plaquetaria, algunas de las cuales se explicarán más adelante. Objetivo: Realizar revisión práctica sobre mutaciones plaquetarias hereditarias de baja incidencia y destacar la importancia de su conocimiento, correcto diagnóstico, y tratamiento precoz. Métodos: Se realizó revisión literaria en inglés y españolen MEDLINE, EMBASE, Lilacs y ScienceDirect desde mayo 2019 hasta abril 2020, con el uso de combinación de palabras clave y términos MeSH relacionados con trombastenia, genética médica, hemostasis, agregación plaquetaria, trombopoyesis. Se efectuó análisis y resumen de la bibliografía revisada. Conclusión: Entre las alteraciones hereditarias de las plaquetas se pueden encontrar defectos en todos los mecanismos en que participan; sin embargo, la confirmación diagnóstica sigue siendo complicada por el tiempo y el costo que representa lo que ocasiona diagnósticos inadecuados que impactan en el manejo clínico y la evolución(AU)

Introduction: Platelets have a key role in primary hemostasis through four main mechanisms: adhesion, aggregation, secretion and procoagulant activity, all of these controlled by over 50 associated genes that have been identified. Clinical signs of hereditary platelets alterations are usually variable; even though these disorders of hemostasis generally course with a notorious thrombocytopenia, they also might have thrombocytopathies, in which the hemostatic capacity of platelets is affected without altering its number. According to this, there's a great variety of phenotypic manifestations and mutations that affect platelet function, some of these will be explained later on. Objective: To make a practical review of hereditary platelets mutations that have low incidence in population and to highlight the importance of knowing about them, how to diagnose them and early treatment. Methods: A review of literature in both Spanish and English, was done based on MEDLINE, EMBASE, Lilacs and ScienceDirect, during May 2019 and April 2020 using key words and MeSH terms such as thrombasthenia, medical genetics, hemostasis, platelets aggregation, thromopoiesis. Then, an analysis and summary of the reviewed bibliography was carried out. Conclusion: Among the hereditary alterations of platelets, many defects can be found in every mechanism involved; however, diagnostic confirmation is still complicated due to time and cost, causing inaccurate diagnoses that impact on clinic management and evolution(AU)