Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 9.340
Filtrar
1.
JSLS ; 26(3)2022.
Artigo em Inglês | MEDLINE | ID: mdl-36071989

RESUMO

Background and Objectives: This retrospective study provides preliminary qualitative assessment of the adverse events (AEs), focusing on pelvic and abdominal AEs and patient outcomes reported for three hemostatic agents used in gynecologic surgery. Methods: Utilization rates for oxidized regenerated cellulose powder (ORC), polysaccharide powder (PSP), and fibrin sealant solution (FSS) were obtained from hospitals via the Premier Healthcare databases for all surgical procedures from January 1, 2018 to September 30, 2020. All reported cases were extracted from the Food and Drug Administration (FDA) Manufacturer and User Facility Device Experience (MAUDE) database for ORC and PSP and from the FDA Adverse Event Reporting System (FAERS) database for FSS. Distributions of AEs by anatomical site (MAUDE/FAERS) and surgical procedures by specialty (Premier) were evaluated for each product. Number of cases and number and types of AEs were compared to the total utilization for each product. Results: PSP was the most used product during the period analyzed (n = 126,509 uses), followed by FSS (n = 80,628 uses), and ORC (n = 41,583 uses). Distribution of surgical procedures by anatomical site varied significantly between hemostatic agents (p < 0.001). ORC was associated with more patient cases with AEs and numbers of reported AEs compared with PSP and FSS (p < 0.001). ORC was associated with higher number of infections than PSP (p < 0.001) and FSS (p < 0.001). Conclusion: These findings suggest that ORC use in abdominal and pelvic surgery may result in more postoperative complications compared with non-ORC hemostatic agents. Further prospective randomized studies are needed to compare efficacy and safety of these products.


Assuntos
Hemostáticos , Feminino , Adesivo Tecidual de Fibrina , Humanos , Pós , Estudos Retrospectivos , Estados Unidos/epidemiologia , United States Food and Drug Administration
2.
Carbohydr Polym ; 296: 119924, 2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-36088022

RESUMO

The development of shape-memory sponge dressings with functions, such as hemostasis, antibacterial activity, and wound healing, is of great significance in clinical applications. Herein, a novel AuNPs@corn stalk/chitin composite sponge (CCAu) was fabricated by crosslinking the chitin matrix with corn stalk-embedded gold nanoparticles (AuNPs). The addition of AuNPs@corn stalk gave the porous chitin sponge shape-recovery ability with improved softness, porosity, and water absorption. Correspondingly, the composite sponge showed better hemostatic effects than commercial PVF sponges. The photothermal effect of AuNPs endowed the composite sponge with excellent antibacterial activity. In addition, the wound treated with composite sponge containing antioxidant AuNPs exhibited a significantly faster wound healing rate (reaching 41.6 % on day 3) than the CH (33.2 %) and control (12.6 %) group through promoting cell migration, angiogenesis and collagen deposition. Therefore, the multifunctional composite sponge with great biocompatibility in this work provides a potential strategy for wound healing.


Assuntos
Hemostáticos , Nanopartículas Metálicas , Antibacterianos/farmacologia , Bandagens/microbiologia , Quitina/farmacologia , Ouro/farmacologia , Hemostasia , Hemostáticos/farmacologia , Cicatrização , Zea mays
3.
Dis Markers ; 2022: 2993309, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36082237

RESUMO

Background: Dyslipidemias are associated with atherosclerotic plaque formation and a prothrombotic state, thus increasing the risk of both atherosclerotic vascular disease and atherothrombotic adverse events. We sought to explore the association between lipoprotein subfractions, overall hemostasis, and coronary calcifications in individuals at intermediate cardiovascular risk. Methods: Consecutive statin-naive individuals at intermediate cardiovascular risk referred for coronary artery calcium score (CACS) scanning were included. CACS was assessed using a 128-slice dual-source CT scanner. Traditional lipid profile, high-density lipoprotein (HDL) subfractions 2 and 3, and small dense low-density lipoproteins (sdLDL) were measured with commercially available assays. Overall hemostatic (OHP) and coagulation potentials (OCP) were measured spectrophotometrically, using fibrin aggregation curves after exposure to thrombin and recombinant tissue-type plasminogen activator, respectively. Overall fibrinolytic potential (OFP) was calculated as a difference between the two areas under curves. Results: We included 160 patients (median age 63 (interquartile range (IQR), 56-71 years, 52% women, and median CACS 8, IQR 0-173 Agatston units). HDL3 levels-but not sdLDL or hemostatic potentials-were significantly associated with CACS zero, even after adjusting for age, sex, arterial hypertension, dyslipidemia, diabetes, and smoking history (OR 0.980 (0.962-0.999), p = 0.034). HDL3 was also significantly associated with OCP (r = -0.232, p adjusted for age and sex 0.037). Conclusions: In patients at intermediate cardiovascular risk, HDL3 is associated with both subclinical atherosclerosis and overall coagulation. Our findings are in line with studies reporting on an inverse relationship between HDL3 and atherosclerosis and provide one possible mechanistic explanation for the association between novel lipid biomarkers and coagulation derangements.


Assuntos
Aterosclerose , Doença da Artéria Coronariana , Dislipidemias , Hemostáticos , Feminino , Hemostasia , Humanos , Lipoproteínas , Lipoproteínas LDL , Masculino , Pessoa de Meia-Idade , Fatores de Risco
4.
Medicina (Kaunas) ; 58(9)2022 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-36143988

RESUMO

Endotheliopathy, according to the "two-activation theory of the endothelium", can be triggered by the activated complement system in critical illnesses, such as sepsis and polytrauma, leading to two distinctly different molecular dysfunctions: (1) the activation of the inflammatory pathway due to the release of inflammatory cytokines, such as interleukin 6 and tumor necrosis factor-α, and (2) the activation of the microthrombotic pathway due to the exocytosis of hemostatic factors, such as ultra-large von Willebrand factor (ULVWF) multimers and FVIII. The former promotes inflammation, including inflammatory organ syndrome (e.g., myocarditis and encephalitis) and multisystem inflammatory syndrome (e.g., cytokine storm), and the latter provokes endotheliopathy-associated vascular microthrombotic disease (VMTD), orchestrating thrombotic thrombocytopenic purpura (TTP)-like syndrome in arterial endotheliopathy, and immune thrombocytopenic purpura (ITP)-like syndrome in venous endotheliopathy, as well as multiorgan dysfunction syndrome (MODS). Because the endothelium is widely distributed in the entire vascular system, the phenotype manifestations of endotheliopathy are variable depending on the extent and location of the endothelial injury, the cause of the underlying pathology, as well as the genetic factor of the individual. To date, because the terms of many human diseases have been defined based on pathological changes in the organ and/or physiological dysfunction, endotheliopathy has not been denoted as a disease entity. In addition to inflammation, endotheliopathy is characterized by the increased activity of FVIII, overexpressed ULVWF/VWF antigen, and insufficient ADAMTS13 activity, which activates the ULVWF path of hemostasis, leading to consumptive thrombocytopenia and microthrombosis. Endothelial molecular pathogenesis produces the complex syndromes of inflammation, VMTD, and autoimmunity, provoking various endotheliopathic syndromes. The novel conceptual discovery of in vivo hemostasis has opened the door to the understanding of the pathogeneses of many endotheliopathy-associated human diseases. Reviewed are the hemostatic mechanisms, pathogenesis, and diagnostic criteria of endotheliopathy, and identified are some of the endotheliopathic syndromes that are encountered in clinical medicine.


Assuntos
Hemostáticos , Trombose , Doenças Vasculares , Endotélio/metabolismo , Endotélio/patologia , Hemostasia , Humanos , Inflamação , Interleucina-6 , Fenótipo , Trombose/patologia , Fator de Necrose Tumoral alfa , Fator de von Willebrand/metabolismo
5.
Trials ; 23(1): 803, 2022 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-36153539

RESUMO

BACKGROUND: The Netherlands Armed Forces have been successfully using deep-frozen (- 80 °C) thrombocyte concentrate (DTC) for the treatment of (massive) bleeding trauma patients in austere environments since 2001. However, high-quality evidence for the effectiveness and safety of DTCs is currently lacking. Therefore, the MAssive transfusion of Frozen bloOD (MAFOD) trial is designed to compare the haemostatic effect of DTCs versus room temperature-stored platelets (RSP) in the treatment of surgical bleeding. METHODS: The MAFOD trial is a single-blinded, randomized controlled non-inferiority trial and will be conducted in three level 1 trauma centres in The Netherlands. Patients 12 years or older, alive at hospital presentation, requiring a massive transfusion including platelets and with signed (deferred) consent will be included. The primary outcome is the percentage of patients that have achieved haemostasis within 6 h and show signs of life. Haemostasis is defined as the time in minutes from arrival to the time of the last blood component transfusion (plasma/platelets or red blood cells), followed by a 2-h transfusion-free period. This is the first randomized controlled study investigating DTCs in trauma and vascular surgical bleeding. DISCUSSION: The hypothesis is that the percentage of patients that will achieve haemostasis in the DTC group is at least equal to the RSP group (85%). With a power of 80%, a significance level of 5% and a non-inferiority limit of 15%, a total of 71 patients in each arm are required, thus resulting in a total of 158 patients, including a 10% refusal rate. The data collected during the study could help improve the use of platelets during resuscitation management. If proven non-inferior in civilian settings, frozen platelets may be used in the future to optimize logistics and improve platelet availability in rural or remote areas for the treatment of (massive) bleeding trauma patients in civilian settings. TRIAL REGISTRATION: ClinicalTrials.gov NCT05502809. Registered on 16 August 2022.


Assuntos
Hemostáticos , Perda Sanguínea Cirúrgica , Plaquetas , Hemostasia , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Temperatura
6.
Adv Gerontol ; 35(3): 435-438, 2022.
Artigo em Russo | MEDLINE | ID: mdl-36169373

RESUMO

The aim of the study was to evaluate the effectiveness of the use of tranexamic acid in the prevention of intraoperative hemorrhagic complications in geriatric patients with bioply transurethral resection of the prostate (BTURP). The patients were divided into 2 groups by the envelope method. Patients of the first group (control group, n=42) did not receive tranexamic acid infusion. Patients of the second group (main group, n=42) received pre-intraoperative infusion of tranexamic acid at a dose of 2 mg/kg. All patients underwent BTURP on endoscopic equipment according to the standard technique under spinal anesthesia. The groups were compared according to the following criteria: the volume of intraoperative blood loss, the level of erythrocytes, platelets and hemoglobin, indicators of hemostasis, thromboelastography before and after surgery. It was established that the perioperative use of tranexamic acid allowed to significantly reduce the volume of blood loss in BTURP. The method of thromboelastography, due to quantitative and qualitative characteristics, is able to assess how the effectiveness of the use of a fibrinolysis inhibitor is achieved.


Assuntos
Antifibrinolíticos , Hemostáticos , Ácido Tranexâmico , Ressecção Transuretral da Próstata , Urologia , Idoso , Antifibrinolíticos/efeitos adversos , Hemostasia , Humanos , Masculino , Ácido Tranexâmico/efeitos adversos , Ressecção Transuretral da Próstata/efeitos adversos
7.
Zh Nevrol Psikhiatr Im S S Korsakova ; 122(9. Vyp. 2): 68-73, 2022.
Artigo em Russo | MEDLINE | ID: mdl-36170102

RESUMO

OBJECTIVE: To reveal paired and partial correlations of values of neuro-immuno-test and thrombodynamics test in children with childhood autism and schizophrenia in childhood in a state of exacerbation. MATERIAL AND METHODS: The study used a database of children with childhood autism, obtained by us in 2028-2019. The study included 46 patients with childhood autism (CA) aged 2 to 13 years: median age [Q1; Q3] - 5 years [4; 7], 10 girls (22%) and 36 boys (78%)). The thrombodynamics test (TD) was performed on a T-2 thrombodynamics analyzer according to the manufacturer's instructions. RESULTS: It was shown that there is a statistically significant positive correlation (R=0.369, p=0.018) between the acquired immunity parameter: the level of serum antibodies to myelin basic protein (BMP): abBMP parameter, and the main parameter of platelet hemostasis - the time of appearance of spontaneous clots (Tsp). It can be assumed that autoantibodies to BMP block the procoagulant effect of myelin basic protein and thus have an anticoagulant effect. However, this analysis did not take into account the possible effects of other parameter of the neuro-immuno-test and thrombodynamics test. Therefore, when studying the correlation of specific parameters of the neuro-immuno-test and thrombodynamics, it is necessary to take into account the possible modifying effect of other parameters of these tests. It was shown that after subtracting the influence on the main correlation (abBMP & Tsp) of individual thrombodynamic parameters (Vi, V and D), as well as their total influence, the partial correlations become statistically insignificant. This indicates that these TD parameters can, individually or in total, determine the revealed correlation between the levels of antibodies to the basic myelin protein (Basic Myelin Protein) and the time of the appearance of spontaneous clots. CONCLUSION: Thus, it was shown that the correlations between the studied parameters of the neuro-immuno-test and the indicators of the thrombodynamics test mutually depend on the other indicators of these tests. This confirms the hypothesis that the immune system and the hemostatic system are two different sides of a single supersystem.


Assuntos
Transtorno Autístico , Hemostáticos , Trombose , Anticoagulantes , Autoanticorpos , Criança , Feminino , Humanos , Masculino , Proteína Básica da Mielina
8.
World J Gastroenterol ; 28(30): 4061-4074, 2022 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-36157107

RESUMO

Chronic liver disease is characterized by several hematological derangements resulting in a complex and barely rebalanced haemostatic environment. Thrombocytopenia is the most common abnormality observed in these patients and recent advances have led to researchers focus the attention on the multifactorial origin of thrombocytopenia and on the key role of thrombopoietin (TPO) in its physiopathology. Severe thrombocytopenia (platelet count < 50000/µL) complicates the management of patients with chronic liver disease by increasing the potential risk of bleeding for invasive procedures, which may be therefore delayed or canceled even if lifesaving. In the very last years, the development of new drugs which exceed the limits of the current standard of care (platelet transfusions, either immediately before or during the procedure) paves the way to a new scenario in the management of this population of patients. Novel agents, such as the TPO-receptor agonists avatrombopag and lusutrombopag, have been developed in order to increase platelet production as an alternative to platelet transfusions. These agents have demonstrated a good profile in terms of efficacy and safety and will hopefully allow reducing limitations and risks associated with platelet transfusion, without any delay in scheduled interventions. Altogether, it is expected that patients with chronic liver disease will be able to face invasive procedures with one more string in their bow.


Assuntos
Hemostáticos , Hepatopatias , Trombocitopenia , Doença Crônica , Hemostáticos/uso terapêutico , Humanos , Hepatopatias/complicações , Hepatopatias/terapia , Transfusão de Plaquetas/efeitos adversos , Trombocitopenia/complicações , Trombocitopenia/terapia , Trombopoetina/uso terapêutico
9.
PLoS Negl Trop Dis ; 16(9): e0010743, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-36070318

RESUMO

Mosquito saliva proteins modulate the human immune and hemostatic systems and control mosquito-borne pathogenic infections. One mechanism through which mosquito proteins may influence host immunity and hemostasis is their interactions with key human receptor proteins that may act as receptors for or coordinate attacks against invading pathogens. Here, using pull-down assays and proteomics-based mass spectrometry, we identified 11 Ae. aegypti salivary gland proteins (SGPs) (e.g., apyrase, Ae. aegypti venom allergen-1 [AaVA-1], neutrophil stimulating protein 1 [NeSt1], and D7 proteins), that interact with one or more of five human receptor proteins (cluster of differentiation 4 [CD4], CD14, CD86, dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin [DC-SIGN], and Toll-like receptor 4 [TLR4]). We focused on CD4- and DC-SIGN-interacting proteins and confirmed that CD4 directly interacts with AaVA-1, D7, and NeST1 recombinant proteins and that AaVA-1 showed a moderate interaction with DC-SIGN using ELISA. Bacteria responsive protein 1 (AgBR1), an Ae. aegypti saliva protein reported to enhance ZIKV infection in humans but that was not identified in our pull-down assay moderately interacts with CD4 in the ELISA assay. Functionally, we showed that AaVA-1 and NeST1 proteins promoted activation of CD4+ T cells. We propose the possible impact of these interactions and effects on mosquito-borne viral infections such as dengue, Zika, and chikungunya viruses. Overall, this study provides key insight into the vector-host (protein-protein) interaction network and suggests roles for these interactions in mosquito-borne viral infections.


Assuntos
Aedes , Flavivirus , Hemostáticos , Infecção por Zika virus , Zika virus , Alérgenos , Animais , Apirase , Humanos , Molécula 3 de Adesão Intercelular/metabolismo , Mosquitos Vetores , Proteínas Recombinantes/metabolismo , Proteínas e Peptídeos Salivares/metabolismo , Receptor 4 Toll-Like/metabolismo
10.
AORN J ; 116(4): 359-367, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36165662

RESUMO

Verifying patient identity before blood product administration Key words: patient identification, patient verification, blood transfusion, blood management, wristband. Surgical site infection risk with allogeneic blood administration Key words: patient blood management, restrictive transfusion triggers, allogeneic blood products, intraoperative blood salvage, surgical site infection. Information on topical thrombin Key words: hemostatic agents, licensed biological product, hemostasis, bovine thrombin, human thrombin. Safe use of topical thrombin Key words: severe adverse events, hemostatic agents, accidental injection, accidental intravascular uptake, product labeling.


Assuntos
Produtos Biológicos , Hemostáticos , Administração Tópica , Animais , Perda Sanguínea Cirúrgica , Bovinos , Hemostasia , Hemostáticos/efeitos adversos , Humanos , Infecção da Ferida Cirúrgica/tratamento farmacológico , Trombina/efeitos adversos
11.
J Adhes Dent ; 24(1): 345-354, 2022 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-36169266

RESUMO

PURPOSE: To investigate the effects of dentin decontamination procedures with ethylenediaminetetraacetic acid (EDTA) after contamination with two hemostatic agents, ViscoStat (VS) and ViscoStat Clear (VSC), on the microtensile bond strength (µTBS) of two different universal adhesives, before and after thermocycling (TC). MATERIALS AND METHODS: Dentin surfaces of 100 human caries-free molars were either contaminated with one of the hemostatic agents or contaminated and then decontaminated with EDTA before the universal adhesives Scotchbond Universal Adhesive (SBU) or Prime & Bond Active (PBA) were applied in self-etch mode. Composite buildups were made and the teeth were sectioned into sticks (n = 90). Half of them immediately underwent the µTBS test, the other half after aging via TC. The data were statistically analyzed using Welch's ANOVA and the Games-Howell post-hoc test (p < 0.05). RESULTS: Significant differences were observed between the groups (p < 0.001). When the dentin surface was contaminated with VSC, TC significantly reduced the mean bond strength, regardless of the universal adhesive. Decontamination with EDTA showed a significant decrease in bond strength after VS contamination and SBU application. The fracture analysis showed mainly adhesive fractures (78.8%) in all test groups. CONCLUSION: As EDTA application did not significantly increase the µTBS of either universal adhesive in self-etch mode in-vitro, it cannot be recommended as a decontaminant.


Assuntos
Colagem Dentária , Hemostáticos , Resinas Compostas , Cimentos Dentários , Dentina , Adesivos Dentinários/química , Ácido Edético/química , Hemostáticos/farmacologia , Humanos , Teste de Materiais , Cimentos de Resina/química , Resistência à Tração
12.
J Feline Med Surg ; 24(10): e353-e359, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36047983

RESUMO

OBJECTIVES: The most common use of plasma transfusion is for haemostatic purposes, but coagulation factor activities in stored feline plasma are unknown. The concentration and stability of coagulation factors I (fibrinogen), II, V, VII, VIII, IX, X, XI and XII in feline fresh frozen plasma (fFFP) stored for 1 year were studied. METHODS: Fifty-five units of fFFP were produced from 55 fresh whole-blood donations obtained from indoor healthy blood donor cats. Twenty-one units were stored for <2 weeks (T0) and 34 were stored for 1 year (T1). After the completion of storage, specific coagulation factor activities for factors II, V, VII, VIII, IX, X, XI and XII were tested using modified one-stage activated partial thromboplastin or prothrombin time assays. Fibrinogen was determined using the Clauss method. RESULTS: Significantly decreased activities were observed for factors II (T0: 101.94% ± 19.06%; T1: 73.23% ± 39.06% [P = 0.001]), VII (T0: 102.78% ± 24.69%; T1: 60.08% ± 38.17% [P <0.001]), VIII (T0: 77.52% ± 30.39%; T1: 50.32% ± 23.8% [P = 0.001]), XI (T0: 88.76% ± 22.73%; T1: 66.28% ± 22.2% [P = 0.001]) and XII (T0: 89.50% ± 21.85%; T1: 55.46% ± 23.18% [P <0.001]) when comparing units at time 0 and after 1 year of storage. No significant difference was observed for factors IX (T0: 84.86% ± 29.35%; T1: 71.37% ± 22.23% [P = 0.064]) and X (T0: 96.24% ± 25.1%; T1: 83.91% ± 49.54% [P = 0.236]). Unexpectedly, a significant increase was observed for factor V (T0: 71.94% ± 24.14%; T1: 97.89% ± 62.33%; P = 0.046). Fibrinogen was 2.76 ± 1.09 g/l at T1. Factors VIII, XII and VII had the lowest mean activities after 1 year. CONCLUSIONS AND RELEVANCE: Although a decrease in most coagulation factors activities was noted with storage, 1-year-old fFFP was haemostatically active in vitro. The most suitable factors for quality control assessment of fFFP are factors VII and VIII. Approximately 13-20 ml/kg of fFFP is required to administer a minimum of 10 IU/kg coagulation factor activity.


Assuntos
Hemostáticos , Plasma , Animais , Transfusão de Componentes Sanguíneos/veterinária , Gatos , Fator V , Fibrinogênio , Tromboplastina
13.
Stroke ; 53(10): 3182-3191, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36069183

RESUMO

BACKGROUND: Spontaneous intracerebral hemorrhage (sICH) is the deadliest stroke subtype with no effective therapies. Limiting hematoma expansion is a promising therapeutic approach. Red blood cell-derived microparticles (RMPs) are novel hemostatic agents. Therefore, we studied the potential of RMPs in limiting hematoma growth and improving outcomes post-sICH. METHODS: sICH was induced in rats by intrastriatal injection of collagenase. RMPs were prepared from human RBCs by high-pressure extrusion. Behavioral and hematoma/lesion volume assessment were done post-sICH. The optimal dose, dosing regimen, and therapeutic time window of RMP therapy required to limit hematoma growth post-sICH were determined. We also evaluated the effect of RMPs on long-term behavioral and histopathologic outcomes post-sICH. RESULTS: RMP treatment limited hematoma growth following sICH. Hematoma volume (mm3) for vehicle- and RMP- (2.66×1010 particles/kg) treated group was 143±8 and 86±4, respectively. The optimal RMP dosing regimen that limits hematoma expansion was identified. RMPs limit hematoma volume when administered up to 4.5-hour post-sICH. Hematoma volume in the 4.5-hour post-sICH RMP treatment group was lower by 24% when compared with the control group. RMP treatment also improved long-term histopathologic and behavioral outcomes post-sICH. CONCLUSIONS: Our results demonstrate that RMP therapy limits hematoma growth and improves outcomes post-sICH in a rodent model. Therefore, RMPs have the potential to limit hematoma growth in sICH patients.


Assuntos
Micropartículas Derivadas de Células , Hemostáticos , Animais , Hemorragia Cerebral/diagnóstico por imagem , Hemorragia Cerebral/tratamento farmacológico , Eritrócitos , Hematoma/diagnóstico por imagem , Hematoma/tratamento farmacológico , Hemostáticos/uso terapêutico , Humanos , Ratos
14.
Int J Mol Sci ; 23(18)2022 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-36142153

RESUMO

Historically, the standard of care for hemophilia A has been intravenous administration of exogenous factor VIII (FVIII), either as prophylaxis or episodically. The development of emicizumab, a humanized bispecific monoclonal antibody mimicking activated FVIII, was a subsequent advance in treatment. However, both exogenous FVIII and emicizumab require repeated and lifelong administration, negatively impacting patient quality of life. A recent breakthrough has been the development of gene therapy. This allows a single intravenous treatment that could result in long-term expression of FVIII, maintenance of steady-state plasma concentrations, and minimization (or possibly elimination) of bleeding episodes for the recipient's lifetime. Several gene therapies have been assessed in clinical trials, with positive outcomes. Valoctocogene roxaparvovec (an adeno-associated viral 5-based therapy encoding human B domain-deleted FVIII) is expected to be the first approved gene therapy in European countries, including Italy, in 2022. Some novel challenges exist including refining patient selection criteria, managing patient expectations, further elucidation of the durability and variability of transgene expression and long-term safety, and the development of standardized 'hub and spoke' centers to optimize and monitor this innovative treatment. Gene therapy represents a paradigm shift, and may become a new reference standard for treating patients with hemophilia A.


Assuntos
Anticorpos Biespecíficos , Hemofilia A , Hemostáticos , Anticorpos Biespecíficos/genética , Anticorpos Biespecíficos/uso terapêutico , Fator VIII/genética , Fator VIII/uso terapêutico , Terapia Genética , Hemofilia A/genética , Hemofilia A/terapia , Humanos , Qualidade de Vida
15.
Int J Mol Sci ; 23(18)2022 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-36142215

RESUMO

The initiation, maintenance and regulation of blood coagulation is inexorably linked to the actions of Zn2+ in blood plasma. Zn2+ interacts with a variety of haemostatic proteins in the bloodstream including fibrinogen, histidine-rich glycoprotein (HRG) and high molecular weight kininogen (HMWK) to regulate haemostasis. The availability of Zn2+ to bind such proteins is controlled by human serum albumin (HSA), which binds 70-85% of plasma Zn2+ under basal conditions. HSA also binds and transports non-esterified fatty acids (NEFAs). Upon NEFA binding, there is a change in the structure of HSA which leads to a reduction in its affinity for Zn2+. This enables other plasma proteins to better compete for binding of Zn2+. In diseases where elevated plasma NEFA concentrations are a feature, such as obesity and diabetes, there is a concurrent increase in hypercoagulability. Evidence indicates that NEFA-induced perturbation of Zn2+-binding by HSA may contribute to the thrombotic complications frequently observed in these pathophysiological conditions. This review highlights potential interventions, both pharmaceutical and non-pharmaceutical that may be employed to combat this dysregulation. Lifestyle and dietary changes have been shown to reduce plasma NEFA concentrations. Furthermore, drugs that influence NEFA levels such as statins and fibrates may be useful in this context. In severely obese patients, more invasive therapies such as bariatric surgery may be useful. Finally, other potential treatments such as chelation therapies, use of cholesteryl transfer protein (CETP) inhibitors, lipase inhibitors, fatty acid inhibitors and other treatments are highlighted, which with additional research and appropriate clinical trials, could prove useful in the treatment and management of thrombotic disease through amelioration of plasma Zn2+ dysregulation in high-risk individuals.


Assuntos
Hemostáticos , Inibidores de Hidroximetilglutaril-CoA Redutases , Trombose , Ácidos Graxos , Ácidos Graxos não Esterificados , Ácidos Fíbricos , Fibrinogênio , Humanos , Cininogênio de Alto Peso Molecular , Lipase , Plasma/metabolismo , Albumina Sérica/metabolismo , Albumina Sérica Humana , Zinco/química
16.
Int J Mol Sci ; 23(18)2022 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-36142580

RESUMO

Hypo- and hyperthermia affect both primary and secondary hemostasis; however, there are controversial data concerning platelet activation and the underlying mechanisms under hypo- and hyperthermia. The discrepancies in the data could be partly explained by different approaches to hemostatic reactions analysis. We applied a new LaSca-TMF laser particle analyzer for a simultaneous fluorescence and laser scattering analysis of platelet responses at different temperatures. Human platelets were activated by ADP in a wide range of temperatures, and platelet transformations (e.g., a shape change reaction, aggregation and clot formation) and the intracellular calcium concentration ([Ca2+]i) were analyzed by LaSca-TMF and confocal microscopy. The platelet shape change reaction gradually increased with a rising temperature. The platelet aggregation strongly decreased at low ADP concentrations with the augmentation of the temperature and was independent of the temperature at high ADP concentrations. In contrast, the clotting time decreased with a temperature increase. Similar to the aggregation response, a rise in [Ca2+]i triggered by low ADP concentrations was higher under hypothermic conditions and the differences were independent of the temperature at high ADP concentrations. We showed that the key reactions of cellular hemostasis are differentially regulated by temperature and demonstrated for the first time that an accelerated aggregation under hypothermic conditions directly correlated with an increased level in [Ca2+]i in platelets.


Assuntos
Plaquetas , Hemostáticos , Difosfato de Adenosina/farmacologia , Plaquetas/fisiologia , Cálcio/farmacologia , Cálcio na Dieta/farmacologia , Hemostasia , Humanos , Ativação Plaquetária , Agregação Plaquetária , Temperatura
17.
Int J Biol Macromol ; 219: 1087-1099, 2022 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-36049562

RESUMO

Timely hemostasis, antibacterial activity, and good adhesion are essential for wound healing. Here, we report about a novel nanocomposite hydrogel with hemostatic, antibacterial, and adhesive properties constructed with a mussel-inspired strategy. Oxidized alginic acid, dopamine, and antimicrobial peptide ε-polylysine were used to prepare a nanocomposite (ODP), and then further cross-linked with acrylamide to fabricate a nanocomposite hydrogel (ODPA). ODPA hydrogel can adhere to the surface of bleeding organs and arrest bleeding within 30 s. It can also be stretched to 12 times its original length and withstand a compression strain of 40 %, and shows effective inhibition on gram-positive and gram-negative bacteria. Compared with commercial alginate sponge, ODPA hydrogel can accelerate the healing of infected full-thickness wound by reducing inflammation, promoting angiogenesis, and collagen deposition. Therefore, the nanocomposite hydrogel is expected to be a multifunctional dressing for promoting healing of infected wounds.


Assuntos
Hemostáticos , Infecção dos Ferimentos , Acrilamidas/farmacologia , Alginatos/química , Ácido Algínico/farmacologia , Antibacterianos/química , Antibacterianos/farmacologia , Peptídeos Antimicrobianos , Colágeno/química , Dopamina/farmacologia , Bactérias Gram-Negativas , Bactérias Gram-Positivas , Hemostáticos/farmacologia , Humanos , Hidrogéis/química , Nanogéis , Polilisina/farmacologia , Cicatrização , Infecção dos Ferimentos/tratamento farmacológico
18.
Int J Biol Macromol ; 219: 1337-1350, 2022 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-36057297

RESUMO

Massive bleeding is a great threat to the life safety of patients, which is a challenging clinical problem. Therefore, it is urgent to develop a kind of multifunctional dressing material with hemostatic ability and antibacterial performance to promote wound healing and repair. To resolve this issue, in this study, a carboxymethyl chitosan (CMCS)/sodium alginate (SA)/oxidized dextran (ODE) (CSO) multifunctional hydrogel was developed. The hydrogel could rapidly gel through Schiff base reaction and amide reaction and firmly adhere to the skin at the wound, to realize the fast hemostasis. Importantly, it was verified that the hydrogel could prevent the Staphylococcus aureus-caused wound infection, owing to the antibacterial effect of CMCS and ODE. In addition, the CSO hydrogel had good water retention capacity and was able to mimic the three-dimensional structure of the natural extracellular matrix, thereby promoting wound repair in mice. In vitro whole-blood clotting assay demonstrated that red blood cells could be adhered to the surface of hydrogel, showing good hemostasis in rat liver injury and tail amputation models. Together with the biocompatible feature, CSO hydrogel holds a great application prospect in hemostasis and wound healing.


Assuntos
Quitosana , Hemostáticos , Infecção dos Ferimentos , Alginatos/química , Amidas/farmacologia , Animais , Antibacterianos/farmacologia , Bandagens , Quitosana/química , Dextranos/farmacologia , Hemostasia , Hemostáticos/farmacologia , Hidrogéis/química , Hidrogéis/farmacologia , Camundongos , Ratos , Bases de Schiff/farmacologia , Água/farmacologia , Cicatrização
19.
Nat Commun ; 13(1): 5492, 2022 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-36123371

RESUMO

Dencichine is a plant-derived nature product that has found various pharmacological applications. Currently, its natural biosynthetic pathway is still elusive, posing challenge to its heterologous biosynthesis. In this work, we design artificial pathways through retro-biosynthesis approaches and achieve de novo production of dencichine. First, biosynthesis of the two direct precursors L-2, 3-diaminopropionate and oxalyl-CoA is achieved by screening and integrating microbial enzymes. Second, the solubility of dencichine synthase, which is the last and only plant-derived pathway enzyme, is significantly improved by introducing 28 synonymous rare codons into the codon-optimized gene to slow down its translation rate. Last, the metabolic network is systematically engineered to direct the carbon flux to dencichine production, and the final titer reaches 1.29 g L-1 with a yield of 0.28 g g-1 glycerol. This work lays the foundation for sustainable production of dencichine and represents an example of how synthetic biology can be harnessed to generate unnatural pathways to produce a desired molecule.


Assuntos
Escherichia coli , Hemostáticos , Diamino Aminoácidos , Códon/metabolismo , Escherichia coli/metabolismo , Glicerol/metabolismo , Engenharia Metabólica , Plantas/genética
20.
Int J Clin Pract ; 2022: 5369001, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36101812

RESUMO

Bleeding disorders are a major group of hematological disorders, which are highly prevalent in the world. Excessive bleeding can result in serious consequences including hypoperfusion and cardiac arrest. The body has its selfmechanism to control excessive bleeding which is termed hemostasis. Hemostasis is achieved in two major steps, the formation of the primary and secondary hemostatic plugs. Endothelium, platelets, and coagulation factors are three components involved in hemostasis. Endothelium and platelets have a major role in forming the primary hemostatic plug. Consequently, the first step in investigating a bleeding disorder is platelet count. Despite normal platelet count, abnormality in the primary hemostatic plug may arise due to functional defects of the platelets including adhesion, activation, and aggregation. Von Willebrand disease (VWD) is an endothelial defect and the most prevalent inherited defect in coagulation. Abnormalities in the secondary hemostatic plug are largely due to coagulation factor deficiencies, and, to a lesser extent, the presence of inhibitors. Techniques involving viscoelastics have been aiding in rapid diagnosis and are useful in point-of-care testing. This article discusses the investigation of bleeding disorders from the perspective of the endothelium, platelet, and coagulation factor physiology. These three components should be properly investigated to achieve the definitive diagnosis of bleeding disorders.


Assuntos
Hemostáticos , Doenças de von Willebrand , Fatores de Coagulação Sanguínea , Plaquetas/fisiologia , Endotélio , Hemorragia/diagnóstico , Humanos , Doenças de von Willebrand/diagnóstico
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...