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1.
Semin Thromb Hemost ; 50(3): 413-422, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37327882

RESUMO

Viscoelastic testing is a clinically available method to assess hypercoagulability. This systematic review aims to provide a comprehensive overview of the existing literature and the potential use of such testing in patients with breast cancer. A systematic literature search for studies investigating the application of viscoelastic testing for patients with breast cancer was conducted. Studies were included as long as they were original, peer-reviewed, and in the English language. Studies were excluded if they were review articles, did not include breast cancer patients, or if the full text was unavailable. This review identified 10 articles that met the inclusion criteria. Two of the studies utilized rotational thromboelastometry, and an additional four studies used thromboelastography, to assess hypercoagulability in patients with breast cancer. Three of the identified articles discussed the use of thromboelastometry in free flap breast reconstruction for patients with breast cancer. One study was a retrospective chart review looking at thromboelastography and microsurgical breast reconstruction. Current literature regarding the application of viscoelastic testing in breast cancer and free flap breast reconstruction is limited, with no randomized trials thus far. However, some studies suggest that there may be potential utility in viscoelastic testing to assess risk for thromboembolism in breast cancer patients, and future research in this area is warranted.


Assuntos
Neoplasias da Mama , Retalhos de Tecido Biológico , Trombofilia , Trombose , Humanos , Feminino , Neoplasias da Mama/complicações , Neoplasias da Mama/cirurgia , Estudos Retrospectivos , Trombofilia/diagnóstico , Trombofilia/etiologia
2.
Br J Dermatol ; 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38531691

RESUMO

BACKGROUND: Interleukin (IL)-13 is a key driver of inflammation and barrier dysfunction in atopic dermatitis (AD). While there is robust evidence that tralokinumab, a monoclonal antibody neutralizing IL-13, reduces inflammation and clinical disease activity, less is known about its effects on barrier function. OBJECTIVES: To characterize effects of tralokinumab treatment on skin barrier function. METHODS: Transepidermal water loss (TEWL), stratum corneum hydration (SCH), natural moisturizing factor (NMF) content, histopathological characteristics, biomarker expression and microbiome composition were evaluated in lesional, non-lesional, and sodium lauryl sulfate (SLS)-irritated skin of 16 AD patients over the course of 16 weeks of tralokinumab treatment. RESULTS: All clinical severity scores decreased significantly over time. At week 16, mean TEWL in target lesions decreased by 32.66% (p = 0.01), and SCH increased by 58.44% (p = 0.004), along with histological reduction in spongiosis (p = 0.003), keratin 16 expression and epidermal thickness (p = 0.001). In parallel, there was a significant decrease in several barrier dysfunction-associated and pro-inflammatory proteins such as fibronectin (p = 0.006), CCL17/TARC (p = 0.025) and IL-8 (p = 0.014), with significant changes already at week 8. Total bacterial load and Staphylococcus aureus abundance were significantly reduced from week 2. CONCLUSION: Tralokinumab treatment improves skin physiology, epidermal pathology, and dysbiosis, further highlighting the pleiotropic role of IL-13 in AD pathogenesis.

3.
Artigo em Inglês | MEDLINE | ID: mdl-38421042

RESUMO

BACKGROUND: Atopic dermatitis (AD) is the most common paediatric inflammatory skin disease. There are currently no robust biomarkers that could reliably predict its manifestation, and on the molecular level, it is less well characterized than adult AD. OBJECTIVES: This study aimed to extend previous findings and provide evidence for distinct changes of the epidermal proteome and microbiome preceding the onset of AD as well as characterizing early AD. METHODS: We longitudinally analysed epidermal biomarker levels and microbial profiles in a cohort of 50 neonates at high risk for AD, who had participated in a randomized controlled trial on early emollient use for AD prevention. RESULTS: About 26% of the infants developed AD until month 24 with an average age of 10 month at disease onset. In children with later AD, IL-1Ra, TNFß, IL-8, IL-18, IL-22, CCL2, TARC, TSLP and VEGFa showed increased levels prior to disease manifestation with levels of IL-1Ra, TNFß and VEGFa already increased shortly after birth. Further, children with later AD displayed a delayed maturation and differentially composed skin microbiome prior to AD onset. At manifestation, levels of multiple Th2, Th17/22 and Th1-associated biomarkers as well as innate immunity markers were elevated, and abundances of commensal Streptococcus species were reduced in favour of Staphylococcus epidermidis. CONCLUSIONS: Our results indicate that elevations of proinflammatory stratum corneum biomarkers and alterations of the skin microbiome precede paediatric AD and characterize the disease at onset.

4.
Semin Thromb Hemost ; 49(2): 192-200, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36252602

RESUMO

Viscoelastic testing (VET), such as thromboelastography, can measure whole blood coagulation dynamics in real time and is used across a range of clinical settings, including cardiac surgery, liver transplant, and trauma. The use of modified thromboelastography with platelet function assessment (TEG(R) PlateletMapping(R) Assay) can provide an analysis of platelet contribution to hemostasis, including the contribution of the P2Y12 receptor and thromboxane pathway to platelet function. The TEG PlateletMapping Assay has shown high correlation with the current gold standard test of platelet function, light transmission aggregometry, to measure arachidonic acid and adenosine diphosphate agonist-induced platelet activation. Studies have also shown comparable results with other whole blood platelet function tests. In this review, we explore the clinical applications of modified thromboelastography with platelet function assessment. This includes guiding dual antiplatelet therapy in relation to cardiac procedures, such as percutaneous coronary interventions, transcatheter aortic valve replacement, and left atrial appendage closure. We also explore the developing use of thromboelastography in the emergency care setting of coronavirus disease 2019, which is commonly associated with a hypercoagulable and hypofibrinolytic state. Despite a general lack of high-quality, grade 1 evidence regarding the use of modified thromboelastography with platelet function assessment in these disease areas, the ability of the TEG PlateletMapping Assay to measure global hemostasis and platelet reactivity rapidly and to view and evaluate results at the point of care makes it a promising area for further study for managing patient treatment and optimizing hemostatic therapy.


Assuntos
COVID-19 , Cardiologia , Humanos , Tromboelastografia/métodos , Hemostasia , Plaquetas
5.
Semin Thromb Hemost ; 49(2): 162-172, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36055266

RESUMO

Patients with cirrhosis often have abnormal hemostasis, with increased risk of hemorrhage and thrombosis. Thromboelastography provides a rapid assessment of the coagulation status and can guide product transfusions in adult patients with cirrhosis. This study aimed to determine whether the use of thromboelastography in adult patients with cirrhosis decreases blood product use and impacts adverse events or mortality compared with standard practice. A registered (PROSPERO CRD42020192458) systematic review and meta-analysis was conducted for randomized controlled trials (RCTs) comparing thromboelastography-guided hemostatic management versus standard practice (control). Co-primary outcomes were the number of transfused platelet units and fresh frozen plasma (FFP) units. Secondary outcomes were mortality, adverse events, utilization of individual blood products, blood loss or excessive bleeding events, hospital/intensive care unit stay, and liver transplant/intervention outcomes. The search identified 260 articles, with five RCTs included in the meta-analysis. Platelet use was five times lower with thromboelastography versus the control, with a relative risk of 0.17 (95% confidence interval [CI]: [0.03-0.90]; p = 0.04), but FFP use did not differ significantly. Thromboelastography was associated with less blood product (p < 0.001), FFP + platelets (p < 0.001), and cryoprecipitate (p < 0.001) use. No differences were reported in bleeding rates or longer term mortality between groups, with the thromboelastography group having lower mortality at 7 days versus the control (relative risk [95% CI] = 0.52 [0.30-0.91]; p = 0.02). Thromboelastography-guided therapy in patients with cirrhosis enhances patient blood management by reducing use of blood products without increasing complications.


Assuntos
Transfusão de Sangue , Tromboelastografia , Adulto , Humanos , Hemorragia/terapia , Cirrose Hepática/complicações , Cirrose Hepática/terapia , Ensaios Clínicos Controlados Aleatórios como Assunto
6.
Allergy ; 78(8): 2290-2300, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37032440

RESUMO

BACKGROUND: Atopic dermatitis (AD) patients display an altered skin microbiome which may not only be an indicator but also a driver of inflammation. We aimed to investigate associations among AD patients' skin microbiome, clinical data, and response to systemic therapy in patients of the TREATgermany registry. METHODS: Skin swabs of 157 patients were profiled with 16S rRNA gene amplicon sequencing before and after 3 months of treatment with dupilumab or cyclosporine. For comparison, 16s microbiome data from 258 population-based healthy controls were used. Disease severity was assessed using established instruments such as the Eczema Area and Severity Index (EASI). RESULTS: We confirmed the previously shown correlation of Staphylococcus aureus abundance and bacterial alpha diversity with AD severity as measured by EASI. Therapy with Dupilumab shifted the bacterial community toward the pattern seen in healthy controls. The relative abundance of Staphylococci and in particular S. aureus significantly decreased on both lesional and non-lesional skin, whereas the abundance of Staphylococcus hominis increased. These changes were largely independent from the degree of clinical improvement and were not observed for cyclosporine. CONCLUSIONS: Systemic treatment with dupilumab but not cyclosporine tends to restore a healthy skin microbiome largely independent of the clinical response indicating potential effects of IL-4RA blockade on the microbiome.


Assuntos
Dermatite Atópica , Microbiota , Humanos , Dermatite Atópica/genética , Ciclosporina/farmacologia , Ciclosporina/uso terapêutico , Staphylococcus aureus/genética , RNA Ribossômico 16S/genética , Pele , Resultado do Tratamento , Índice de Gravidade de Doença
7.
Transfusion ; 63(12): 2256-2264, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37839089

RESUMO

BACKGROUND: Source plasma collections are needed to satisfy the growing demand for plasma-derived medicinal products. The US plasma collection target volume has been guided by a standard weight-based FDA-issued nomogram (STAN) since 1992. In this research, large-scale US-based real-world data (RWD) were analyzed to confirm the safety and volume gains of a newly introduced personalized nomogram (PERS) that was previously studied in a premarket randomized controlled environment. STUDY DESIGN AND METHODS: A non-inferiority (NI) analysis was conducted to compare the novel nomogram's significant hypotensive adverse event (AE) incidence rate with large historical standard nomogram AE datasets. Additionally, the average target volumes and donor return rates were compared for collections following PERS and STAN. RESULTS: A total of 4,816,784 donations (PERS) by 414,957 donors resulted in a rate of 0.0998% (95% CI [0.0970, 0.1027]) significant hypotensive AEs. NI analysis suggested strong non-inferiority of the new technology (Δ = -0.0082%, 95% CI [-0.0113, -0.0050], prespecified NI margin = 0.1080). Average plasma collection target volumes increased by 66.39 mL (8.49%; p < .0001). Consecutive weekly donor return rates were consistent between the two nomograms (PERS: 73.6%, 95% CI [69.6%-76.7%]; STAN: 74.1%, 95% CI [66.1%-77.2%]). DISCUSSION: This analysis confirms in a large-scale real-world dataset the key safety parameter and collection benefit of a novel, technology-enabled nomogram. The nomogram may help meet the growing demand for plasma-derived therapies by providing approximately 8.5% more plasma per donation on average while maintaining donor safety and return rates.


Assuntos
Hipotensão , Nomogramas , Humanos , Doadores de Sangue , Análise de Dados
8.
Acta Derm Venereol ; 103: adv5671, 2023 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-37246806

RESUMO

Several small studies have indicated that daily emollient use from birth might delay, suppress or prevent atopic dermatitis (AD). Two larger trials did not confirm this; however, a recent smaller study indicated a protective effect if daily emollient use is used in the first 2 months of life. Further research is needed to evaluate the effect of emollient use on development of AD. The current study randomly assigned 50 newborns who were at high risk of developing AD (1:1) to receive general infant skin-care advice (control group), or skin-care advice plus emollient with advice to apply emollient at least once daily until 1 year of age (intervention group). Repeated skin examinations, skin physiology measurements and skin microbiome profiling were performed. Of the children in the intervention and control groups, 28% and 24%, respectively, developed AD (adjusted Relative Risk (RR) 1.19, p = 0.65, adjusted risk difference 0.05). Skin pH decreased and transepidermal water loss and stratum corneum hydration increased over time in both groups with no significant differences. In the intervention group skin microbiome alpha diversity increased earlier, and the abundance of Streptococcus and Staphylococcus species were significantly reduced at month 1. Daily early emollient use in children with high risk of AD was safe, but it did not significantly reduce the risk of developing AD or impact skin physiology development.


Assuntos
Dermatite Atópica , Emolientes , Criança , Humanos , Lactente , Recém-Nascido , Dermatite Atópica/diagnóstico , Dermatite Atópica/tratamento farmacológico , Dermatite Atópica/prevenção & controle , Emolientes/efeitos adversos , Projetos Piloto , Pele , Fenômenos Fisiológicos da Pele , Resultado do Tratamento
9.
Transfus Apher Sci ; 61(6): 103470, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35667962

RESUMO

BACKGROUND AND OBJECTIVES: There is less robust data describing adverse events (AEs) in source plasma donors than in whole blood donors, particularly regarding time to AEs (TAEs). We, therefore, sought to characterize TAE and the influence of donor characteristics in a large-scale clinical trial dataset. MATERIALS AND METHODS: TAE was calculated utilizing data from the IMPACT (IMproving PlasmA CollecTion) trial, with linear regression analyses performed to determine the influence of donor parameters on TAE. RESULTS: Linear regression revealed that repeat donors tended to have AEs ~6 min later than naïve donors in the IMPACT trial; however, this was not statistically significant (p = 0.781). Besides this, gender showed greatest difference in TAE; however, no covariates were statistically significant. AE rates were relatively constant throughout the donation process with higher rates beginning 40 min after initiation; no initial peak was observed (first 10-15 min). CONCLUSION: AEs occurred throughout the donation process. None of the analyzed factors could fully explain the difference in the dynamics of AE timing with that of whole blood donation, particularly the missing early peak. Therefore, other factors, e.g., expectation and attitude towards donating plasma and potential events during plasma collection, may explain this difference and should be the focus of future studies.


Assuntos
Doadores de Sangue , Plasma , Humanos , Ensaios Clínicos como Assunto
10.
Platelets ; 33(4): 520-530, 2022 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-34369848

RESUMO

We carried out a literature search in MEDLINE (PubMed) and EMBASE literature databases to provide a concise review of the role of viscoelastic testing in assessing peri-interventional platelet function and coagulation. The search identified 130 articles that were relevant for the review, covering the basic science of VHA and VHA in clinical settings including cardiac surgery, cardiology, neurology, trauma, non-cardiac surgery, obstetrics, liver disease, and COVID-19. Evidence from these articles is used to describe the important role of VHAs and platelet function testing in various peri-interventional setups. VHAs can help us to comprehensively assess the contribution of platelets and coagulation dynamics to clotting at the site-of-care much faster than standard laboratory measures. In addition to standard coagulation tests, VHAs are beneficial in reducing allogeneic transfusion requirements and bleeding, in predicting ischemic events, and improving outcomes in several peri-interventional care settings. Further focused studies are needed to confirm their utility in the peri-interventional case.


Assuntos
Transtornos da Coagulação Sanguínea , COVID-19 , Coagulação Sanguínea , Testes de Coagulação Sanguínea , Hemostasia , Humanos , Tromboelastografia
11.
Transfusion ; 61(10): 2849-2854, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34309028

RESUMO

BACKGROUND: The IMPACT trial demonstrated the safety of a new personalized nomogram for plasma donation and provided an opportunity to explore short- to mid-term impact on repeat donation and deferral rates, and factors affecting these. STUDY DESIGN AND METHODS: In the IMPACT trial, participants were randomized to donate plasma using an established weight-based nomogram (control) versus a new personalized nomogram incorporating height, weight, and hematocrit (experimental). In this exploratory analysis, repeat donations (per donor, by study arm) were analyzed using negative binomial generalized linear regression models and descriptive statistics. The mean number of donor deferral events was compared between the two arms using logistic regression and count data modeling approaches and were analyzed by lead cause. RESULTS: The predicted mean number of repeat donations was similar between the control and experimental arms (6.82 vs. 6.62, respectively; p = .22). Overall, the predicted mean number of repeat donations was significantly higher in males compared with females (p < .0001). Naïve donors had on average 2.8/2.7 (control/experimental) fewer repeat donations compared with experienced donors. In 23, 137 donations from 3443 donors, 798 donors (376 control, 422 experimental, p = .80) had at least one deferral (for any cause). The predicted mean number of deferrals in all categories of interest was not statistically different between the study arms. CONCLUSION: Similar repeat donation and deferral rates between arms suggest that the new nomogram did not result in disruptions to subsequent donation. Further longitudinal research on mid- to long-term effects is warranted.


Assuntos
Doadores de Sangue , Bancos de Sangue , Doadores de Sangue/estatística & dados numéricos , Estatura , Peso Corporal , Feminino , Hematócrito , Humanos , Modelos Lineares , Masculino , Estados Unidos
12.
Transfusion ; 61(6): 1789-1798, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33760230

RESUMO

BACKGROUND: Source plasma is essential to support the growing demand for plasma-derived medicinal products. Supply is short, with donor availability further limited by the coronavirus disease 2019 (COVID-19) pandemic. This study examined whether a novel, personalized, technology-based nomogram was noninferior with regard to significant hypotensive adverse events (AEs) in healthy donors. STUDY DESIGN AND METHODS: IMPACT (IMproving PlasmA CollecTion) was a prospective, multicenter, double-blinded, randomized, controlled trial carried out between January 6 and March 26, 2020, in three U.S plasma collection centers. Donors were randomly assigned to the current simplified 1992 nomogram (control) or a novel percent plasma nomogram (PPN) with personalized target volume calculation (experimental). Primary endpoint was the rate of significant hypotensive AEs. Noninferiority (NI) was tested with a margin of 0.15%. Collected plasma volume was a secondary endpoint. RESULTS: A total of 3443 donors (mean [SD] BMI: 32 [7.74] kg/m2 ; 65% male) underwent 23,137 donations (median [range]: 6 [1-22] per subject). Ten significant hypotensive AEs were observed (six control; four experimental), with model-based AE incidence rate estimates (95% CI) of 0.051% (0.020%-0.114%) and 0.035% (0.010%-0.094%), respectively (p = .58). NI was met at an upper limit of 0.043% versus the predefined margin of 0.15%. There was no statistical difference between total AEs (all AE types: p = .32). Mean plasma volume collected was 777.8 ml (control) versus 841.7 ml (experimental); an increase of 63.9 ml per donation (8.2%; p < .0001). CONCLUSION: This trial showed that a novel personalized nomogram approach in healthy donors allowed approximately 8% more plasma per donation to be collected without impairing donor safety.


Assuntos
Segurança do Sangue/métodos , Coleta de Amostras Sanguíneas/métodos , Voluntários Saudáveis , Nomogramas , Medicina de Precisão/métodos , Adulto , Doadores de Sangue/classificação , COVID-19/sangue , COVID-19/epidemiologia , Seleção do Doador/métodos , Feminino , Humanos , Invenções , Masculino , Pessoa de Meia-Idade , Pandemias , Plasmaferese , Reação Transfusional/prevenção & controle , Adulto Jovem
13.
HPB (Oxford) ; 23(3): 331-343, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33229277

RESUMO

BACKGROUND: The objective of the current study was to summarize and evaluate all published evidence regarding viscoelastic testing in the field of liver surgery. METHODS: A systematic search of the literature was performed using Medline/PubMed, Scopus, Cochrane Library Central, Google Scholar, and clinicaltrials.gov databases. The following keywords were used:"Thromboelastography", "Thromboelastometry", "Viscoelastic tests OR testing", "Sonoclot Devices", "Point-of-care tests OR testing", "Coagulation OR Haemostasis OR Hemostasis", "Liver OR Hepatic Surgery", "Cirrhosis." RESULTS: A total of 12 studies analyzing 348 patients who underwent viscoelastic testing of coagulation during liver surgery for benign or malignant diseases were included; 7 (58.3%) studies reported on the use of thromboelastography (TEG), and 5 (41.7%) reported on rotational thromboelastometry (ROTEM). Viscoelastic testing (TEG and ROTEM) identified normo-, hyper- and hypo-coagulable status in 77% (n = 268/348), 18.4% (n = 64/348), and 4.6% (n = 16/348) of patients, respectively. In contrast, conventional coagulation tests indicated normo-coagulability in 111 patients (34.2% out of 325) and hypo-coagulability in 214 (65.8% out of 325) patients following liver resection. No patient (0% out of 291) experienced postoperative hemorrhage, whereas 5.8% (n = 17/291) experienced postoperative thromboembolic events. CONCLUSIONS: Global viscoelastic testing may be a reasonable adjunct to conventional coagulation testing to provide a more robust assessment of the coagulation status of patients undergoing liver surgery.


Assuntos
Transtornos da Coagulação Sanguínea , Coagulação Sanguínea , Transtornos da Coagulação Sanguínea/diagnóstico , Testes de Coagulação Sanguínea , Humanos , Fígado/cirurgia , Tromboelastografia
14.
Semin Thromb Hemost ; 46(2): 134-146, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32160640

RESUMO

This article explores the application of viscoelastic tests (VETs) in trauma-induced coagulopathy and trauma resuscitation. We describe the advantages of VETs over conventional coagulation tests in the trauma setting and refer to previous disciplines in which VET use has reduced blood product utilization, guided prohemostatic agents, and improved clinical outcomes such as the mortality of critically bleeding patients. We describe different VETs and provide guidance for blood component therapy and prohemostatic therapy based on specific VET parameters. Because the two most commonly used VET systems, rotational thromboelastometry and thromboelastography, use different activators and have different terminologies, this practical narrative review will directly compare and contrast these two VETs to help the clinician easily interpret either and use the interpretation to determine hemostatic integrity in the bleeding trauma patient. Finally, we anticipate the future of new viscoelastic technologies that can be used in this setting.


Assuntos
Transtornos da Coagulação Sanguínea/diagnóstico , Transtornos da Coagulação Sanguínea/terapia , Tromboelastografia/métodos , Ferimentos e Lesões/sangue , Humanos , Ferimentos e Lesões/complicações
15.
Transfusion ; 60 Suppl 6: S101-S121, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-33089936

RESUMO

Viscoelastic tests (VETs) have been used routinely for liver transplantation, cardiac surgery, and trauma, but only recently have found clinical utility in benign hematologic disorders. Therefore, guidelines for diagnosis and treatment of these disorders based on viscoelastic variables have been adapted from the existing transplant, cardiothoracic surgery, and trauma resuscitation literature. As a result, diagnostic and therapeutic strategies for benign hematologic disorders utilizing VETs are not uniform. Accordingly, even though there has been a recent increase in the utilization of VET for the diagnosis and treatment of such disorders, the literature is still in its early stages. Analysis of point-of-care viscoelastic tracings from benign hematologic disorders has the potential to allow prompt recognition of disease and to guide patient-specific intervention. Here we present a review describing the application of VETs to benign hematologic disorders.


Assuntos
Doenças Hematológicas/sangue , Testes Imediatos , Tromboelastografia , Animais , Doenças Autoimunes/sangue , Transtornos da Coagulação Sanguínea/sangue , Transtornos da Coagulação Sanguínea/genética , Transfusão de Componentes Sanguíneos , Modelos Animais de Doenças , Previsões , Hemostasia/fisiologia , Humanos , Tromboelastografia/instrumentação , Tromboelastografia/métodos , Trombofilia/sangue , Trombofilia/etiologia , Trombofilia/genética , Trombofilia/imunologia , Vasculite/sangue
16.
Transfusion ; 60 Suppl 6: S86-S100, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-33089937

RESUMO

The quantification of the coagulopathic state associated with oncologic and hematologic diseases is imperfectly assessed by common coagulation tests such as prothrombin time, activated partial thromboplastin time, fibrinogen levels, and platelet count. These tests provide a static representation of a component of hemostatic integrity, presenting an incomplete picture of coagulation in these patients. Viscoelastic tests (VETs), such as rotational thromboelastometry (ROTEM) and thromboelastography (TEG), as whole blood analyses, provide data related to the cumulative effects of blood components and all stages of the coagulation and fibrinolytic processes. The utility of VETs has been demonstrated since the late 1960s in guiding blood component therapy for patients undergoing liver transplantation. Since then, the scope of viscoelastic testing has expanded to become routinely used for cardiac surgery, obstetrics, and trauma. In the past decade, VETs' expanded usage has been most significant in trauma resuscitation. However, use of VETs for patients with malignancy-associated coagulopathy (MAC) and hematologic malignancies is increasing. For the purposes of this narrative review, we discuss the similarities between trauma-induced coagulopathy (TIC) and MAC. These similarities center on the thrombomodulin-thrombin complex as it switches between the thrombin-activatable fibrinolysis inhibitor coagulation pathway and activating the protein C anticoagulation pathway. This produces a spectrum of coagulopathy and fibrinolytic alterations ranging from shutdown to hyperfibrinolysis that are common to TIC, MAC, and hematologic malignancies. There is expanding literature regarding the utility of TEG and ROTEM to describe the hemostatic integrity of patients with oncologic and hematologic conditions, which we review here.


Assuntos
Transtornos da Coagulação Sanguínea/sangue , Fibrinólise , Neoplasias/sangue , Tromboelastografia/métodos , Antineoplásicos/efeitos adversos , Coagulação Sanguínea/fisiologia , Transtornos da Coagulação Sanguínea/diagnóstico , Transtornos da Coagulação Sanguínea/etiologia , Medicina Baseada em Evidências , Doenças Hematológicas/sangue , Neoplasias Hematológicas/sangue , Humanos , Neoplasias/complicações , Policitemia Vera/sangue , Tromboelastografia/instrumentação , Trombocitopenia/sangue , Trombocitopenia/induzido quimicamente , Ferimentos e Lesões/sangue , Ferimentos e Lesões/complicações
17.
Environ Sci Technol ; 54(3): 1451-1463, 2020 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-31909604

RESUMO

The discovery of methane (CH4) accumulation in oxic marine and limnic waters has redefined the role of aquatic environments in the regional CH4 cycle. Although CH4 accumulation in oxic surface waters became apparent in recent years, the sources are still subject to controversial discussions. We present high-resolution in situ measurements of CH4 concentration and its stable isotope composition in a stratified mesotrophic lake. We show that CH4 accumulation in surface waters originates from a highly dynamic interplay between (oxic) CH4 production and emission to the atmosphere. Laboratory incubations of different phytoplankton types and application of stable isotope techniques provide a first unambiguous evidence that major phytoplankton classes in Lake Stechlin per se produce CH4 under oxic conditions. Combined field and lab results show that the photoautotroph community is an important driver for CH4 production and its highly dynamic accumulation in oxic surface waters.


Assuntos
Lagos , Metano , Atmosfera
18.
J Thromb Thrombolysis ; 50(1): 135-143, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31620937

RESUMO

In the context of interventional cardiology, platelet function testing may identify patients treated with P2Y12-inhibitors at an increased risk of mortality, thrombosis and bleeding. Several whole blood point-of-care platelet function analyzers are available; however, inter-device differences have not been examined systematically. To compare three platelet function tests under standardized in vitro conditions. Healthy volunteer (n = 10) blood samples were spiked with increasing concentrations of ticagrelor (0-7500 ng/mL) and/or ASA (0-3280 ng/mL), measured on three platelet function analyzers (TEG®6s, Multiplate®, and VerifyNow®) and respective Effective Concentration (EC) levels EC10, EC50 and EC90 were calculated. Repeatability was assessed in a separate group of pooled blood samples (n = 10) spiked with ticagrelor at EC10, EC50 and EC90. ASA had no impact on ADP-activated channels for all three devices. TEG®6s was able to distinguish (p ≤ 0.05) between all ticagrelor EC zones; VerifyNow® and Multiplate® were able to distinguish between three and two zones, respectively. Multiplate® showed the largest window between EC10 and EC90 (19-9153 ng/mL), followed by TEG®6s (144-2589 ng/mL), and VerifyNow® (191-1100 ng/mL). Drug effect models distribution of disagreements were identified for TEG®6s (5.0%), VerifyNow® (8.3%), and Multiplate® (13.3%). TEG®6s showed the smallest average coefficient of variation between EC conditions (5.1%), followed by Multiplate® (14.1%), and VerifyNow® (17.7%). Linear models could be generated between TEG®6s and Multiplate®, but not VerifyNow®. Significant differences were found between whole blood point-of-care platelet function analyzers and the clinical impact of these differences needs to be further investigated.


Assuntos
Testes de Função Plaquetária , Ticagrelor/farmacologia , Coagulação Sanguínea/efeitos dos fármacos , Pesquisa Comparativa da Efetividade , Monitoramento de Medicamentos/métodos , Voluntários Saudáveis , Humanos , Inibidores da Agregação Plaquetária/farmacologia , Testes de Função Plaquetária/instrumentação , Testes de Função Plaquetária/métodos , Testes de Função Plaquetária/normas , Testes Imediatos , Antagonistas do Receptor Purinérgico P2Y/farmacologia
19.
Platelets ; 31(7): 932-938, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-31878831

RESUMO

Knowledge of platelet count and function is key to ensuring appropriate hemostatic management. We hypothesized that the novel, portable TEG®6s coagulation assessment system could evaluate the contribution of both platelet count and function to clot formation. Whole-blood samples with variable platelet counts were prepared from healthy volunteers. Platelet function was adjusted using seven concentrations of abciximab and evaluated by light transmission aggregometry (LTA) with TRAP agonist. Maximum amplitude (MA), reaction time (R) and activated clotting time (ACT) were assessed in citrated kaolin (CK), CK with heparinase (CKH), citrated RapidTEG® (CRT), and citrated functional fibrinogen (CFF) assays. Positive correlations were observed between platelet count and CK.MA, CKH.MA, and CRT.MA (p < .0001), and CK.R, CKH.R, and CRT.ACT (p < .05). Platelet count could be accurately quantified in the range 28-91 k/µL, 28-86 k/µL and 28-74 k/µL for CK.MA, CKH.MA, and CRT.MA, respectively. CK.MA, CKH.MA, and CRT.MA showed significant negative relationships with abciximab concentration (p < .001). Platelet function inhibition was detected by all three assays at >68% measured by LTA and quantified in the range 68.4-82% (CK), 69.4-88% (CKH), and 69.7-76% (CRT). This demonstrates the TEG®6s analyzer can accurately evaluate platelet count and function at the site-of-care.


Assuntos
Testes de Coagulação Sanguínea/métodos , Contagem de Plaquetas/métodos , Testes de Função Plaquetária/métodos , Trombose/sangue , Feminino , Humanos , Masculino
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