How Protein Depletion Balances Thrombosis and Bleeding Risk in the Context of Platelet's Activatory and Negative Signaling.

Platelets are small cell fragments that play a crucial role in hemostasis, requiring fast response times and fine signaling pathway regulation. For this regulation, platelets require a balance between two pathway types: the activatory and negative signaling pathways. Activatory signaling mediators are positive responses that enhance stimuli initiated by a receptor in the platelet membrane. Negative signaling regulates and controls the responses downstream of the same receptors to roll back or even avoid spontaneous thrombotic events. Several blood-related pathologies can be observed when these processes are unregulated, such as massive bleeding in activatory signaling inhibition or thrombotic events for negative signaling inhibition. The study of each protein and metabolite in isolation does not help to understand the role of the protein or how it can be contrasted; however, understanding the balance between active and negative signaling could help develop effective therapies to prevent thrombotic events and bleeding disorders.

O-GlcNAcylation: Crosstalk between Hemostasis, Inflammation, and Cancer.

O-linked ß-N-acetylglucosamine (O-GlcNAc, O-GlcNAcylation) is a post-translational modification of serine/threonine residues of proteins. Alterations in O-GlcNAcylation have been implicated in several types of cancer, regulation of tumor progression, inflammation, and thrombosis through its interaction with signaling pathways. We aim to explore the relationship between O-GlcNAcylation and hemostasis, inflammation, and cancer, which could serve as potential prognostic tools or clinical predictions for cancer patients' healthcare and as an approach to combat cancer. We found that cancer is characterized by high glucose demand and consumption, a chronic inflammatory state, a state of hypercoagulability, and platelet hyperaggregability that favors thrombosis; the latter is a major cause of death in these patients. Furthermore, we review transcription factors and pathways associated with O-GlcNAcylation, thrombosis, inflammation, and cancer, such as the PI3K/Akt/c-Myc pathway, the nuclear factor kappa B pathway, and the PI3K/AKT/mTOR pathway. We also review infectious agents associated with cancer and chronic inflammation and potential inhibitors of cancer cell development. We conclude that it is necessary to approach both the diagnosis and treatment of cancer as a network in which multiple signaling pathways are integrated, and to search for a combination of potential drugs that regulate this signaling network.

International Society on Thrombosis and Haemostasis clinical practice guideline for treatment of congenital hemophilia A and B based on the Grading of Recommendations Assessment, Development, and Evaluation methodology.

BACKGROUND: Hemophilia is a rare congenital bleeding disorder that results from complete or partial deficiency of blood coagulation factor (F)VIII (hemophilia A) or FIX (hemophilia B) due to pathogenic variants in their coding genes. Hemophilia requires complex management. To date, there is no evidence-based clinical practice guideline on hemophilia treatment based on the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. OBJECTIVES: This evidence-based clinical practice guideline from the International Society on Thrombosis and Haemostasis aims to provide an overview of evidence and support patients, caregivers, hematologists, pediatricians, other clinicians, researchers, and stakeholders in treatment decisions about congenital hemophilia A and B. METHODS: The International Society on Thrombosis and Haemostasis formed a multidisciplinary guideline panel of physicians and patients with global representation, balanced to minimize potential bias from conflicts of interest. The panel prioritized a set of clinical questions and outcomes according to their importance for clinicians and patients. A methodological team supported the guideline development process, including searching for evidence and performing systematic reviews. The GRADE approach was used, including GRADE Evidence to Decision frameworks. The recommendations were subject to public comment. RESULTS: The panel selected 13 questions, of which 11 addressed the treatment of hemophilia A and 2 the treatment of hemophilia B. Specifically, the panel addressed questions on prophylactic and episodic treatment with FVIII concentrates, bypassing agents, and nonfactor therapy (emicizumab) for hemophilia A (with and without inhibitors) as well as immune tolerance induction for hemophilia A. For hemophilia B, the panel addressed questions on prophylactic and episodic treatment of bleeding events with FIX concentrates. Agreement was reached for all 13 recommendations, of which 7 (54%) were based on evidence from randomized clinical trials, 3 (23%) on observational studies, and 3 (23%) on indirect comparisons. CONCLUSION: Strong recommendations were issued for prophylactic over episodic treatment for severe and moderately severe hemophilia A and B. Only conditional recommendations were issued for the remaining questions. Future research should focus on direct treatment comparisons and the treatment of hemophilia B with and without inhibitors. Future updates of this guideline will provide an updated evidence synthesis on the current questions and focus on new FVIII and FIX concentrates, novel nonfactor therapies, and gene therapy for severe and nonsevere hemophilia A and B.

Guidelines for the management of coagulation disorders in patients with cirrhosis.

Coagulation management in the patient with cirrhosis has undergone a significant transformation since the beginning of this century, with the concept of a rebalancing between procoagulant and anticoagulant factors. The paradigm that patients with cirrhosis have a greater bleeding tendency has changed, as a result of this rebalancing. In addition, it has brought to light the presence of complications related to thrombotic events in this group of patients. These guidelines detail aspects related to pathophysiologic mechanisms that intervene in the maintenance of hemostasis in the patient with cirrhosis, the relevance of portal hypertension, mechanical factors for the development of bleeding, modifications in the hepatic synthesis of coagulation factors, and the changes in the reticuloendothelial system in acute hepatic decompensation and acute-on-chronic liver failure. They address new aspects related to the hemorrhagic complications in patients with cirrhosis, considering the risk for bleeding during diagnostic or therapeutic procedures, as well as the usefulness of different tools for diagnosing coagulation and recommendations on the pharmacologic treatment and blood-product transfusion in the context of hemorrhage. These guidelines also update the knowledge regarding hypercoagulability in the patient with cirrhosis, as well as the efficacy and safety of treatment with the different anticoagulation regimens. Lastly, they provide recommendations on coagulation management in the context of acute-on-chronic liver failure, acute liver decompensation, and specific aspects related to the patient undergoing liver transplantation.

Hemostasis Using Prothrombin Complex Concentrate in Patients Undergoing Cardiac Surgery: Systematic Review with Meta-Analysis.

OBJECTIVE: The purpose of present study was to comprehensívely explore the efficacy and safety of prothrombín complex concentrate (PCC) to treat massíve bleedíng in patíents undergoing cardiac surgery. METHODS: PubMed®, Embase, and Cochrane Líbrary databases were searched for studíes ínvestigating PCC administratíon duríng cardiac surgery published before September 10, 2022. Mean dífference (MD) wíth 95% confidence interval (CI) was applíed to analyze continuous data, and dichotomous data were analyzed as risk ratio (RR) with 95% CI. RESULTS: Twelve studies were included in the meta-analysis. Compared with other non-PCC treatment regimens, PCC was not assocíated with elevated mortality (RR=1.18, 95% CI=0.86-1.60, P=0.30, I2=0%), shorter hospital stay (MD=-2.17 days; 95% CI=-5.62-1.28, P=0.22, I2=91%), reduced total thoracic drainage (MD=-67.94 ml, 95% CI=-239.52-103.65, P=0.44, I2=91%), thromboembolíc events (RR=1.10, 95% CI=0.74-1.65, P=0.63, I2=39%), increase ín atríal fibríllatíon events (RR=0.73, 95% CI=0.52-1.05, P=0.24, I2=29%), and myocardial infarction (RR=1.10, 95% CI=0.80-1.51, P=0.57, I2=81%). However, PCC use was associated with reduced intensive care unit length of stay (MD=-0.81 days, 95% CI=-1.48- -0.13, P=0.02, I2=0%), bleeding (MD=-248.67 ml, 95% CI=-465.36- -31.97, P=0.02, I2=84%), and intra-aortic balloon pump/extracorporeal membrane oxygenation (RR=0.65, 95% CI=0.42-0.996, P=0.05, I2=0%) when compared with non-PCC treatment regimens. CONCLUSION: The use of PCC in cardiac surgery did not correlate with mortality, length of hospítal stay, thoracic drainage, atríal fibríllatíon, myocardíal ínfarction, and thromboembolíc events. However, PCC sígnificantly improved postoperatíve intensíve care unít length of stay, bleedíng, and intra-aortic balloon pump/ extracorporeal membrane oxygenation outcomes ín patients undergoing cardíac surgery.

Consensus of the Brazilian association of hematology, hemotherapy and cellular therapy on patient blood management: Intraoperative hemostasis and volume replacement

Abstract Hemostasis plays a critical role in surgical procedures and is essential for a successful outcome. Advances in hemostatic agents offer new approaches to controlling bleeding thereby making surgeries safer. The appropriate choice of these agents is crucial. Volume replacement, another integral part of Patient Blood Management (PBM), maintains adequate tissue perfusion, preventing cellular damage. Individualization in fluid administration is vital with the choice between crystalloids and colloids depending on each case. Colloids, unlike crystalloids, increase oncotic pressure, contributing to fluid retention in the intravascular space. Understanding these aspects is essential to ensure safe and effective surgery, minimizing complications related to blood loss and maintaining the patient's hemodynamic status.

Adaptation And Use of the Papworth Haemostasis Checklist - Clinical Outcomes Analysis at Hospital Estadual Mário Covas.

INTRODUCTION: Postoperative bleeding is one of the main causes of complications in cardiovascular surgery, which highlights the importance of ensuring adequate intraoperative hemostasis, providing a better patient outcome. This study aimed to improve the prevention of postoperative bleeding in the Cardiovascular Surgery Department of the Hospital Estadual Mário Covas (Santo André, Brazil) using an adapted version of the Papworth Haemostasis Checklist to assess the impact of this standardization on bleeding rate, postoperative complications, reoperation, and mortality. METHODS: This is a non-randomized controlled clinical trial, whose non-probabilistic sample consisted of patients undergoing cardiac surgery in the abovementioned service within a two-year interval. The Papworth Haemostasis Checklist was adapted to the Brazilian laboratory parameters and the questions were translated into Portuguese. This checklist was used before the surgeon started the chest wall closure. Patients were followed up until 30 days after surgery. A P-value < 0.05 was considered statistically relevant. RESULTS: This study included 200 patients. After the checklist, a reduction in 24-hour drain output, postoperative complications, and reoperation was observed, although statistical significance was not reached. Finally, there was a significant reduction in the number of deaths (8 vs. 2; P=0.05). CONCLUSION: The use of the adapted checklist in our hospital proved to be an effective intervention to improve the prevention of postoperative bleeding, with a direct impact in the number of deaths in the study period. The reduction in deaths was possible thanks to the reduction in the bleeding rate, postoperative complications, and reoperations for bleeding.

Innovations in RNA therapy for hemophilia.

Given the shortcomings of current factor-, nonfactor-, and adeno-associated virus gene-based therapies, the recent advent of RNA-based therapeutics for hemophilia is changing the fundamental approach to hemophilia management. From small interfering RNA therapeutics that knockdown clot regulators antithrombin, protein S, and heparin cofactor II, to CRISPR/Cas9 gene editing that may personalize treatment, improved technologies have the potential to reduce bleeds and factor use and avoid inhibitor formation. These novel agents, some in preclinical studies and others in early phase trials, have the potential to simplify treatment and improve hemostasis and quality of life. Furthermore, because these therapies arise from manipulation of the coagulation cascade and thrombin generation and its regulation, they will enhance our understanding of hemostasis and thrombosis and ultimately lead to better therapies for children and adults with inherited bleeding disorders. What does the future hold? With the development of novel preclinical technologies at the bench, there will be fewer joint bleeds, debilitating joint disease, orthopedic surgery, and improved physical and mental health, which were not previously possible. In this review, we identify current limitations of treatment and progress in the development of novel RNA therapeutics, including messenger RNA nanoparticle delivery and gene editing for the treatment of hemophilia.

Statins and Hemostasis: Therapeutic Potential Based on Clinical Evidence.

Hemostasis preserves blood fluidity and prevents its loss after vessel injury. The maintenance of blood fluidity requires a delicate balance between pro-coagulant and fibrinolytic status. Endothelial cells (ECs) in the inner face of blood vessels maintain hemostasis through balancing anti-thrombotic and pro-fibrinolytic activities. Dyslipidemias are linked to hemostatic alterations. Thus, it is necessary a better understanding of the underlying mechanisms linking hemostasis with dyslipidemia. Statins are drugs that decrease cholesterol levels in the blood and are the gold standard for treating hyperlipidemias. Statins can be classified into natural and synthetic molecules, approved for the treatment of hypercholesterolemia. The classical mechanism of action of statins is by competitive inhibition of a key enzyme in the synthesis pathway of cholesterol, the HMG-CoA reductase. Statins are frequently administrated by oral ingestion and its interaction with other drugs and food supplements is associated with altered bioavailability. In this review we deeply discuss the actions of statins beyond the control of dyslipidemias, focusing on the actions in thrombotic modulation, vascular and cardiovascular-related diseases, metabolic diseases including metabolic syndrome, diabetes, hyperlipidemia, and hypertension, and chronic diseases such as cancer, chronic obstructive pulmonary disease, and chronic kidney disease. Furthermore, we were prompted to delved deeper in the molecular mechanisms by means statins regulate coagulation acting on liver, platelets, and endothelium. Clinical evidence show that statins are effective regulators of dyslipidemia with a high impact in hemostasis regulation and its deleterious consequences. However, studies are required to elucidate its underlying molecular mechanism and improving their therapeutical actions.

Effects of Adrenergic Receptor Stimulation on Human Hemostasis: A Systematic Review.

Catecholamine stimulation over adrenergic receptors results in a state of hypercoagulability. Chronic stress involves the release and increase in circulation of catecholamines and other stress related hormones. Numerous observational studies in human have related stressful scenarios to several coagulation variables, but controlled stimulation with agonists or antagonists to adrenergic receptors are scarce. This systematic review is aimed at presenting an updated appraisal of the effect of adrenergic receptor modulation on variables related to human hemostasis by systematically reviewing the effect of adrenergic receptor-targeting drugs on scale variables related to hemostasis. By searching 3 databases for articles published between January 1st 2011 and February 16th, 2022 reporting effects on coagulation parameters from stimulation with α- or ß-adrenergic receptor targeting drugs in humans regardless of baseline condition, excluding records different from original research and those not addressing the main aim of this systematic review. Risk of bias assessed using the Revised Cochrane risk-of-bias tool for randomized trials (RoB 2). Tables describing a pro-thrombotic anti-fibrinolytic state induced after ß-adrenergic receptor agonist stimulation and the opposite after α1-, ß-adrenergic receptor antagonist stimulation were synthesized from 4 eligible records by comparing hemostasis-related variables to their baseline. Notwithstanding this low number of records, experimental interventions included were sound and mostly unbiased, results were coherent, and outcomes were biologically plausible. In summary, this systematic review provides a critical systematic assessment and an updated elaboration, and its shortcomings highlight the need for further investigation in the field of hematology.

Association of hemostasis and inflammation biomarkers with outcomes in acute coronary syndromes.

Plaque rupture triggers a prothrombotic response that is counterbalanced by a fibrinolytic response. d -dimer serves as a marker of both processes. Inflammatory mediators are also released, evidenced with the rise of high-sensitive C reactive protein (hsCRP). Current evidence with these biomarkers has shown conflicting results. Determine an association between d -dimer and hsCRP within hospital and 1-year mortality in patients with acute coronary syndromes. In total, 127 patients were included. In-hospital mortality was 5.7%, and 1-year all-cause and cardiovascular mortality were 14.6 and 9.7%, respectively. The median of admission d -dimer for patients who died during hospital stay was higher than those who survived [4.59 (interquartile ranges (IQR) 1.94-6.05 µg/ml fibrinogen equivalent units (FEU)) vs. 0.56 (IQR 0.31-1.12 µg/ml FEU), P  = 0.001]. At 1-year follow-up, the median of admission d -dimer for patients who died was significantly higher than those who survived: 1.55 (IQR 0.91-5.08 µg/ml FEU) vs. 0.53 (IQR 0.29-0.90 µg/ml FEU), P  < 0.001. Positive d -dimer vs. negative d -dimer at admission analysis evidenced that almost 25% of the positive patients were dead at 1-year follow-up (22.4 vs. 2.4% negative d -dimer, P  = 0.011). Multivariate logistic regression analysis showed that d -dimer has an independent association with 1-year mortality [odds ratio 1.06 (95% confidence interval 1.02-1.10), P  = 0.006]. Positive significative correlations between d -dimer and hsCRP levels ( R  = 0.56, P  < 0.001) were found. High levels of admission d -dimer were strongly associated with in-hospital and 1-year mortality. Significant correlations with hsCRP could explain the inflammatory nature that led to poorer outcomes. d -dimer could be useful in risk stratification in acute coronary syndromes; however, a specific threshold should be defined for this type of patient.

Impacts of ischemic preconditioning in liver resection: systematic review with meta-analysis.

OBJECTIVE: To assess the beneficial effects of ischemic preconditioning (IPC) in liver resection and evaluate its applicability in clinical practice. SUMMARY BACKGROUND DATA: Liver surgeries are usually associated with intentional transient ischemia for hemostatic control. IPC is a surgical step that intends to reduce the effects of ischemia-reperfusion; however, there is no strong evidence about the real impact of the IPC, and it is necessary to effectively clarify what its effects are. METHODS: Randomized clinical trials were selected, comparing IPC with no preconditioning in patients undergoing liver resection. Data were extracted by three independent researchers according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, Supplemental Digital Content 1, http://links.lww.com/JS9/A79 . Several outcomes were evaluated, including postoperative peaks of transaminases and bilirubin, mortality, length of hospital stay, length of stay in the ICU, bleeding, and transfusion of blood products, among others. Bias risks were assessed using the Cochrane collaboration tool. RESULTS: Seventeen articles were selected, with a total of 1052 patients. IPC did not change the surgical time of the liver resections while these patients bled less (Mean Difference: -49.97 ml; 95% CI: -86.32 to -13.6; I2 : 64%), needed less blood products [relative risk (RR): 0.71; 95% CI: 0.53-0.96; I2 =0%], and had a lower risk of postoperative ascites (RR: 0.40; 95% CI: 0.17-0.93; I2 =0%). The other outcomes had no statistical differences or could not have their meta-analyses conducted due to high heterogeneity. CONCLUSIONS: IPC is applicable in clinical practice, and it has some beneficial effects. However, there is not enough evidence to encourage its routine use.

Bioactive compounds and functional foods as coadjuvant therapy for thrombosis.

Cardiovascular diseases (CVDs) are the leading cause of death. The most common cardiovascular pathologies are thromboembolic diseases. Antithrombotic therapy prevents thrombus formation or dissolves that previously constituted. However, it presents a high rate of accidents such as gastric bleeding and cerebrovascular embolism. Plant foods and their secondary metabolites have been reported to regulate blood hemostasis. This review article aims to propose plant foods and their metabolites as adjuvant therapy for the management of thromboembolic diseases. Various databases were consulted, using antiplatelet, anticoagulant, and fibrinolytic as key terms. In total, 35 foods and 24 secondary metabolites, via in vitro, in vivo, and clinical studies, have been reported to regulate platelet aggregation, blood coagulation, and fibrinolysis. According to the studies presented in this review, plant foods with effects at concentrations less than 50 µg mL-1 and secondary metabolites with IC50 less than 100 µM can be considered agents with high antithrombotic potential. This review suggests that plant foods and their secondary metabolites should be used to develop foods, ingredients and nutraceuticals with functional properties. The evidence presented in this review shows that plant foods and their bioactive compounds could be used as adjuvants for the treatment and prevention of thrombotic complications. However, further in vivo and clinical trials are required to establish effective and safe doses.

Hemostasis control after femoral percutaneous approach: A systematic review and meta-analysis.

BACKGROUND: Hemostasis control after percutaneous endovascular procedures through the femoral approach remains challenging for catheterization laboratory nurses, given method variability. OBJECTIVE: To summarize the available evidence on vascular devices efficacy dedicated to hemostasis control compared to the extrinsic compression after percutaneous procedures in the femoral vein or artery. METHODS: A systematic review with meta-analysis of randomized clinical trials was conducted. We compared different hemostasis methods in adult patients who underwent diagnostic and/or therapeutic procedures through femoral access. The databases searched were PubMed, Embase, CINAHL and Cochrane CENTRAL, and updated on 03/2022. The outcomes included hematoma, pseudoaneurysm, bleeding, minor and major vascular complication, time to hemostasis, device failure, and manual compression repetition. The risk of bias was assessed using the Cochrane Risk of Bias Tool 1.0. Pooled effect sizes on continuous, categorical and proportion variables were estimated with the random effects model. The continuous variables were summarized as the difference between means weighted by the inverse of variance (WMD), and the categorical ones by the summary of relative risks (RR), estimated by the DerSimonian and Laird method. The Freeman-Tukey method was used to estimate the summary effect of proportions. RESULTS: Fifty articles were included in the systematic review. When compared to extrinsic compression, vascular closure devices resulted in a relative risk reduction (RRR) for hematoma: RR 0.82 [95%CI 0.72 to 0.94] and in shorter time to hemostasis WMD -15.06 min [95%CI -17.56 to -12.56]; no association was observed between interventions with vascular closure devices and extrinsic compression for pseudoaneurysm, bleeding, minor and major vascular complications. Compared to extrinsic compression, sealant or gel type devices were compatible with a RRR for hematoma: RR 0.73 [95%CI 0.59 to 0.90]; and metal clip or staple type devices for pseudoaneurysm: RR 0.48 [95%CI 0.25 to 0.90]; and major vascular complication: RR 0.33 [95%CI 0.17 to 0.64]. For each 100 observations, the device failure rate for metal clip or staple was 3.28% [95%CI 1.69 to 6.27]; for suture 6.84% [95%CI 4.93 to 9.41]; for collagen 3.15% [95%CI 2.24 to 4.41]; and for sealant or gel 7.22% [95% CI 5.49 to 9.45]. CONCLUSIONS: Vascular closure devices performed better in hemostasis control. The certainty of the evidence was rated as very low to moderate. REGISTRATION: PROSPERO CRD42019140794.

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.

Metabolomic and proteomic profiling in bipolar disorder patients revealed potential molecular signatures related to hemostasis.

INTRODUCTION: Bipolar disorder (BD) is a mood disorder characterized by the occurrence of depressive episodes alternating with episodes of elevated mood (known as mania). There is also an increased risk of other medical comorbidities. OBJECTIVES: This work uses a systems biology approach to compare BD treated patients with healthy controls (HCs), integrating proteomics and metabolomics data using partial correlation analysis in order to observe the interactions between altered proteins and metabolites, as well as proposing a potential metabolic signature panel for the disease. METHODS: Data integration between proteomics and metabolomics was performed using GC-MS data and label-free proteomics from the same individuals (N = 13; 5 BD, 8 HC) using generalized canonical correlation analysis and partial correlation analysis, and then building a correlation network between metabolites and proteins. Ridge-logistic regression models were developed to stratify between BD and HC groups using an extended metabolomics dataset (N = 28; 14 BD, 14 HC), applying a recursive feature elimination for the optimal selection of the metabolites. RESULTS: Network analysis demonstrated links between proteins and metabolites, pointing to possible alterations in hemostasis of BD patients. Ridge-logistic regression model indicated a molecular signature comprising 9 metabolites, with an area under the receiver operating characteristic curve (AUROC) of 0.833 (95% CI 0.817-0.914). CONCLUSION: From our results, we conclude that several metabolic processes are related to BD, which can be considered as a multi-system disorder. We also demonstrate the feasibility of partial correlation analysis for integration of proteomics and metabolomics data in a case-control study setting.

Safety profile of repeated infusion of platelet-like nanoparticles in healthy dogs.

OBJECTIVE: To assess the safety and efficacy of the platelet-like nanoparticle (PLN), and to assess its safety in repeated administration. ANIMALS: 6 purpose-bred dogs. PROCEDURES: The PLN was administered IV at 3 different doses using a randomized crossover design. Each dog received a full dose of 8 X 1010 particles/10 kg, half dose, and 10 times the dose, with a 14-day washout period between doses. Biochemical, prothrombin time, partial thromboplastin time, and fibrinogen analyses were performed at baseline and 96 hours postinfusion. A CBC, kaolin-activated thromboelastography, platelet function assay closure time, and buccal mucosal bleeding time were performed at baseline and 1, 6, 24, 48, 72, and 96 hours postinfusion. RESULTS: No significant changes were observed over time in the thromboelastography parameters, closure time, and buccal mucosal bleeding time. After the administration of the half dose, hematocrit levels decreased significantly at 1, 6, 24, 48, and 96 hours, with all values within the reference range. The platelet count was decreased significantly at hours 1, 6, 24, 48, and 72 after administration of the half dose, with values less than the reference range at all hours but hour 72. No significant changes in serum biochemistry, coagulation panel, and fibrinogen were observed for all doses. No adverse events were noted during the first infusion. Three dogs experienced transient sedation and nausea after repeat infusion. CLINICAL RELEVANCE: The PLN resulted in a dilution of hematocrit and platelets, and did not significantly alter hemostasis negatively. The safety of repeated doses should be investigated further in dogs.