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BACKGROUND: This study explored the effects of hyperbaric oxygen therapy (HBOT) on hemogram, serum biochemistry and hemostatic variables in female dogs undergoing laparoscopic-assisted ovariohysterectomy (OVH). MATERIALS: Thirty adult, mixed-breed, healthy female dogs were randomly divided into the following three groups: HBOT + SURG (exposed to two absolute atmospheres (ATAs) for 45 min followed by laparoscopic-assisted OVH), HBOT (exposed to two ATAs for 45 min) and SURG (laparoscopic-assisted OVH). Blood samples were collected at T0 (at the admission), at T1, 24 h after T0 (immediately after HBOT in the HBOT + SURG and HBOT groups, and immediately before anesthetic premedication in the SURG group), and at T2, 48 h after T0 (24 h after HBOT and anesthetic premedication). METHODS: Assessments included erythrogram, leukogram, thrombogram, renal and hepatic serum biochemistry, prothrombin time (PT), activated partial thromboplastin time (APTT), buccal mucosal bleeding time (BMBT) and bloodstain area (BA) on hygroscopic paper collected at the BMBT. RESULTS: Both the HBOT + SURG and SURG groups presented neutrophilia (p ≤ 0.0039) at T2 and an increase of ALP at T2 (p ≤ 0.0493), the SURG group presented an increase in leukocyte count at T2 (p = 0.0238) and the HBOT + SURG group presented a reduction in lymphocyte count at T2 (p = 0.0115). In the HBOT + SURG group, there was a reduction in PT and APTT in relation to the baseline value (p ≤ 0.0412). CONCLUSIONS: A session of HBOT at two ATAs for 45 min did not cause changes in the BMBT or BA in healthy female dogs. Some blood parameters investigated (neutrophil and lymphocyte count, ALP, PT and APTT) were affected by the use of HBOT.
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Coagulation activation in immunothrombosis involves various pathways distinct from classical hemostasis, offering potential therapeutic targets to control inflammation-induced hypercoagulability while potentially sparing hemostasis. The Angiopoietin/Tie2 pathway, previously linked to embryonic angiogenesis and sepsis-related endothelial barrier regulation, was recently associated with coagulation activation in sepsis and COVID-19. This study explores the connection between key mediators of the Angiopoietin/Tie2 pathway and coagulation activation. The study included COVID-19 patients with hypoxia and healthy controls. Blood samples were processed to obtain platelet-free plasma, and frozen until analysis. Extracellular vesicles (EVs) in plasma were characterized and quantified using flow cytometry, and their tissue factor (TF) procoagulant activity was measured using a kinetic chromogenic method. Several markers of hemostasis were assessed. Levels of ANGPT1, ANGPT2, and soluble Tie2 correlated with markers of coagulation and platelet activation. EVs from platelets and endothelial cells were increased in COVID-19 patients, and a significant increase in TF+ EVs derived from endothelial cells was observed. In addition, ANGPT2 levels were associated with TF expression and activity in EVs. In conclusion, we provide further evidence for the involvement of the Angiopoietin/Tie2 pathway in the coagulopathy of COVID-19 mediated in part by release of EVs as a potential source of TF activity.
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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.
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Insuficiência Hepática Crônica Agudizada , Transtornos da Coagulação Sanguínea , Humanos , Insuficiência Hepática Crônica Agudizada/complicações , Transtornos da Coagulação Sanguínea/complicações , Transtornos da Coagulação Sanguínea/terapia , Cirrose Hepática/complicações , Cirrose Hepática/terapia , Coagulação Sanguínea , HemostasiaRESUMO
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.
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Thrombosis is currently among the major causes of morbidity and mortality in the World. New prevention and therapy alternatives have been increasingly sought in medicinal plants. In this context, we have been investigating parsley, Petroselinum crispum (Mill.) Nym, an aromatic herb with two leaf varieties. We report here the in vitro, in vivo, and ex vivo anti-hemostatic and antithrombotic activities of a parsley curly-leaf variety. Aqueous extracts of aerial parts (PCC-AP), stems (PCC-S), and leaves (PCC-L) showed significant in vitro antiplatelet activity. PCC-AP extract exhibited the highest activity (IC50 2.92 mg/mL) when using ADP and collagen as agonists. All extracts also presented in vitro anticoagulant activity (APTT and PT) and anti-thrombogenic activity. PCC-S was the most active, with more significant interference in the factors of the intrinsic coagulation pathway. The oral administration of PCC-AP extract in rats caused a greater inhibitory activity in the deep vein thrombi (50%; 65 mg/kg) than in arterial thrombi formation (50%; 200 mg/kg), without cumulative effect after consecutive five-day administration. PCC-AP extract was safe in the induced bleeding time test. Its anti-aggregating profile was similar in ex vivo and in vitro conditions but was more effective in the extrinsic pathway when compared to in vitro results. Apiin and coumaric acid derivatives are the main compounds in PCC-AP according to the HPLC-DAD-ESI-MS/MS profile. We demonstrated for the first time that extracts from different parts of curly parsley have significant antiplatelet, anticoagulant, and antithrombotic activity without inducing hemorrhage, proving its potential as a source of antithrombotic compounds.
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Fibrinolíticos , Petroselinum , Extratos Vegetais , Folhas de Planta , Animais , Petroselinum/química , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Folhas de Planta/química , Ratos , Masculino , Fibrinolíticos/farmacologia , Fibrinolíticos/isolamento & purificação , Fibrinolíticos/química , Ratos Wistar , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/isolamento & purificação , Trombose/tratamento farmacológico , Inibidores da Agregação Plaquetária/farmacologia , Inibidores da Agregação Plaquetária/isolamento & purificação , Componentes Aéreos da Planta/química , Caules de Planta/química , Hemostáticos/farmacologia , Hemostáticos/isolamento & purificação , Anticoagulantes/farmacologia , Anticoagulantes/isolamento & purificação , Anticoagulantes/química , Plantas Medicinais/químicaRESUMO
Patient Blood Management (PBM) is a holistic approach to managing blood as a resource of each patient; it is a multimodal strategy that is implemented using a set of techniques that can be applied in individual cases. In fact, the overall result of the implementation of PBM cannot be fully appreciated or explained by simply summing up the effects of the individual strategies and techniques used, since they can only produce the expected ideal result if combined. Implementing a PBM program in healthcare offers several benefits including improved patient safety, better outcomes, cost savings, conservation of resources, evidence-based practice, transfusion alternatives, improved quality of care, compliance with accreditation standards, patient-centered care, and professional education and training.
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INTRODUCTION: Thrombotic disorders are among the leading causes of morbidity and mortality worldwide. Drugs used in the prevention and treatment of atherothrombosis have pharmacokinetic limitations and adverse effects such as hemorrhagic conditions, highlighting the importance of developing more effective antiplatelet agents. ethod: In this work, we synthesized N,N'-disubstituted ureas 3a-3j and evaluated their antiplatelet profiles through in vitro, ex vivo, and in silico studies. The synthesized derivatives exhibited a selective inhibitory profile against platelet aggregation induced by arachidonic acid (AA) in vitro, without significantly affecting other aspects of primary hemostasis and blood coagulation. The compounds that showed inhibition greater than 85% were submitted to the analysis of their potency by calculating the concentration required to inhibit 50% of platelet aggregation induced by AA (IC50). Urea derivative 3a was the most potent with IC50 of 1.45 µM. Interestingly, this derivative inhibited more than 90% of platelet aggregation induced by AA ex vivo, with a similar effect to acetylsalicylic acid. In the hemolysis assay, most of the urea derivatives presented values below 10% suggesting good hemocompatibility. Additionally, the compounds tested at 100 µM also showed no cytotoxic effects in HepG2 and Vero cells. RESULT: The in silico results suggested that compound 3a may bind to the key residue of COX-1 similar to AA and known COX-1 inhibitors, and the results are also in agreement with our SAR, which suggests that the inhibition of this enzyme is the most likely mechanism of antiplatelet activity. CONCLUSION: Therefore, these results demonstrated that N,N'-disubstituted ureas are promising candidates for the development of novel antiplatelet agents.
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The aims of this study are to characterize the antiplatelet activity of StSBTc-3, a potato serine protease with fibrino (geno) lytic activity, and to provide information on its mechanism of action. The results obtained show that StSBTc-3 inhibits clot retraction and prevents platelet aggregation induced by thrombin, convulxin, and A23187. Platelet aggregation inhibition occurs in a dose-dependent manner and is not affected by inactivation of StSBTc-3 with the inhibitor of serine proteases phenylmethylsulfonyl fluoride (PMSF). In addition, StSBTc-3 reduces fibrinogen binding onto platelets. In-silico calculations show a high binding affinity between StSBTc-3 and human α2bß3 integrin suggesting that the antiplatelet activity of StSBTc-3 could be associated with the fibronectin type III domain present in its amino acid sequence. Binding experiments show that StSBTc-3 binds to α2bß3 preventing the interaction between α2bß3 and fibrinogen and, consequently, inhibiting platelet aggregation. StSBTc-3 represents a promising compound to be considered as an alternative to commercially available drugs used in cardiovascular therapies.
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Solanum tuberosum , Humanos , Serina/metabolismo , Plaquetas/metabolismo , Agregação Plaquetária , Serina Endopeptidases/metabolismo , Fibrinogênio/metabolismo , Subtilisinas/metabolismoRESUMO
Abstract Hemostasis is a complex set of biological processes responsible for blood fluidity within normal vessels and for the physiological interruption of bleeding in cases of vascular injury. Bothrops moojeni snake venom is rich in bioactive compounds of pharmacological and clinical interest since its protein components are capable of interfering with many points of the hemostatic process. Here, we present the B. moojeni venom proteins that affect hemostasis and discuss their pharmacological and clinical potential. This systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol. Data were obtained from the CAPES Journal Portal database, using the terms "Bothrops" AND "hemostasis", in a search for scientific articles made available in the last 20 years. Many components isolated from B. moojeni snake venom are characterized for their effect on hemostasis and possible application in the diagnosis and treatment of hemostatic disorders.
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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.