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BACKGROUND: The combination of rivaroxaban plus aspirin compared with aspirin alone reduces the risk of major adverse cardiovascular and limb events for high-risk patients with peripheral artery disease. It is unknown whether rivaroxaban plus aspirin improves intermittent claudication for adults with lower-risk peripheral arterial disease. METHODS: In this randomized, open-label, multicenter, 24-week clinical trial, we randomly assigned patients with peripheral artery disease and intermittent claudication to receive either 2.5 mg of rivaroxaban twice daily plus 100 mg of aspirin once daily or 100 mg of aspirin once daily. The primary outcome was a 24-week change in total walking distance, measured by the 6-minute walking test. The primary safety outcome was the incidence of major bleeding or clinically relevant nonmajor bleeding. RESULTS: Eighty-eight patients were randomly assigned to either rivaroxaban plus aspirin (n=46) or aspirin alone (n=42). The mean age was 67 years, and 54% were female. The total walking distance measured by 6-minute walk test improved by 89 ± 18 m (mean±standard error) in the rivaroxaban-plus-aspirin group versus 21 ± 16 m in the aspirin-alone group. This corresponded to an absolute difference of 68 ± 24 m (95% confidence interval [CI], 19 to 116 m; P=0.007) and a relative improvement over the aspirin-alone group of 327% (95% CI, 94 to 560%). No major bleeding events were observed in either group. CONCLUSIONS: In patients with peripheral artery disease and intermittent claudication, 2.5 mg of rivaroxaban twice daily plus 100 mg of aspirin daily improved the total walking distance by a 6-minute walking test compared with 100 mg of aspirin daily alone. (Funded by Bayer S.A.; Clinicaltrials.gov number, NCT04853719.).
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Aspirina , Inibidores do Fator Xa , Claudicação Intermitente , Doença Arterial Periférica , Rivaroxabana , Humanos , Rivaroxabana/uso terapêutico , Rivaroxabana/administração & dosagem , Rivaroxabana/efeitos adversos , Claudicação Intermitente/tratamento farmacológico , Feminino , Masculino , Idoso , Aspirina/uso terapêutico , Aspirina/administração & dosagem , Aspirina/efeitos adversos , Pessoa de Meia-Idade , Inibidores do Fator Xa/uso terapêutico , Inibidores do Fator Xa/administração & dosagem , Inibidores do Fator Xa/efeitos adversos , Inibidores do Fator Xa/farmacologia , Doença Arterial Periférica/tratamento farmacológico , Inibidores da Agregação Plaquetária/uso terapêutico , Inibidores da Agregação Plaquetária/administração & dosagem , Inibidores da Agregação Plaquetária/efeitos adversos , Quimioterapia Combinada , Resultado do Tratamento , Hemorragia/induzido quimicamenteRESUMO
In patients with end-stage renal disease (ESRD), heart failure with reduced ejection fraction (HFrEF) is a common comorbidity. Thromboinflammatory processes in both conditions represent complex pathophysiology, demonstrated by dysregulation of thromboinflammatory biomarkers, and commonly resulting in the combined pathology of cardiorenal syndrome. We sought to investigate the effects of HFrEF on these biomarkers in patients with ESRD, and observe the relationship to mortality. Blood samples from 73 patients with ESRD (mean age 67 ± 13 years, 56% male) and 40 healthy controls were analyzed via enzyme-linked immunosorbent assay and other chromogenic methods for angiopoietin-2 (Ang2), endogenous glycosaminoglycans, fatty acid binding protein, interleukin-6, lipopolysaccharide, free fatty acids, NT-pro B-type natriuretic peptide, tumor necrosis factor α, vascular endothelial growth factor, and von Willebrand factor. Patients were stratified into those with or without HFrEF (EF < 50%). Patients had highly prevalent comorbidities including coronary artery disease 46%, diabetes 69%, hypertension 97%, and smoking 49%. Most biomarkers were upregulated in ESRD compared to controls. Patients with HFrEF and ESRD had greater interleukin-6 and NT-pro B-type natriuretic peptide and lesser lipopolysaccharide compared to ESRD only. Spearman correlations between most biomarkers were increased in HFrEF + ESRD over ESRD only. Ang-2 was associated with mortality in this cohort. The dysregulation of thromboinflammation in ESRD is somewhat amplified in comorbid HFrEF. Correlation among biomarkers in this cohort indicates the mechanisms of thromboinflammatory biomarker generation in ESRD and HFrEF share an integrative process. Ang2, interleukin-6, and lipopolysaccharide show promise as biomarkers for risk stratification among patients with both HFrEF and ESRD.
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Biomarcadores , Insuficiência Cardíaca , Falência Renal Crônica , Humanos , Masculino , Biomarcadores/sangue , Feminino , Falência Renal Crônica/sangue , Insuficiência Cardíaca/sangue , Idoso , Pessoa de Meia-Idade , Inflamação/sangueRESUMO
Pulmonary embolism (PE) is a heterogenous condition with variable clinical presentations. Thrombin generation potential (TGP) and biomarkers, and blood cellular indices can reflect the underlying pathophysiology and risk stratification of PE. This case-control study analyzed TGP in 209 PE patients from Loyola University, Pulmonary Embolism Response Team program compared to normal human plasma (NHP) controls. The present study evaluates TGP and biomarkers, and cellular indices in relation to PE severity, according to the European Society of Cardiology (ESC) guidelines. Statistical analysis including median with interquartile range (IQR), 2-tailed Wilcoxon Mann-Whitney test, Chi-square test, and Spearman Correlational analysis were performed. There were 209 patients with PE, with an almost equal distribution between sex, and a median age of 63 years. Significant downregulation in peak thrombin and endogenous thrombin potential (ETP), as well as upregulation in lag time, were observed in PE patients versus controls. Biomarker analysis revealed pronounced elevations, with D-dimer demonstrating the most significant increase. Blood cellular indices also rose in PE patients, correlating with disease severity. PE severity was associated with higher TGP and biomarker levels. Mortality rates differed significantly across risk categories and were highest in patients with elevated cellular indices. TGP and biomarkers are intricately linked to PE severity and can aid in risk stratification. Elevated cellular indices are associated with increased mortality, highlighting their potential as prognostic markers. These findings could enhance the precision of PE management strategies.
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Biomarcadores , Embolia Pulmonar , Trombina , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Biomarcadores/sangue , Estudos de Casos e Controles , Embolia Pulmonar/sangue , Trombina/metabolismo , Trombina/biossíntese , Trombina/análiseRESUMO
Cardiovascular disease is a prevalent complication in patients with end-stage renal disease (ESRD) on maintenance hemodialysis. In the ESRD patient population, cardiovascular mortality is 20 times higher compared to the general population. The strong relationship between both illnesses can be explained through cardiorenal syndrome (CRS). CRS encompasses a spectrum of disorders involving both the heart and kidneys in which acute or chronic dysfunction in one organ may induce a similar effect in the other organ. Current literature reveals that inflammation and thrombosis are integral to CRS development. Hence, this study aims to demonstrate whether thromboinflammatory biomarkers and laboratory parameters correlate with ESRD progression and the development of CRS. Ninety-five ESRD patients were recruited at Loyola University Medical Center hemodialysis unit. Epic chart analysis was used to determine patients with CRS. Biomarkers (C-reactive protein, tumor necrosis factor alpha, interleukin-6, Annexin V, L-fatty acid binding protein, monocyte chemoattractant protein 1, nitric oxide, von Willebrand factor, D-dimer, and plasminogen activator inhibitor-1) were profiled using the enzyme-linked immunosorbent assay method in patients with and without CRS in the ESRD cohort. All biomarkers were significantly elevated in ESRD patients compared to normal controls (P < .05) and laboratory parameters, ferritin (521.99 ± 289.33) and PTH (442.91 ± 1.50). Through EPIC chart analysis 47% of ESRD patients have CRS. D-dimer and TNF-α were significantly elevated in patients with CRS compared to patients without CRS. This study suggests that biomarkers, D-dimer, and TNF-α, can be good predictors of CRS in ESRD patients.
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Biomarcadores , Síndrome Cardiorrenal , Falência Renal Crônica , Humanos , Biomarcadores/sangue , Feminino , Falência Renal Crônica/sangue , Falência Renal Crônica/complicações , Falência Renal Crônica/terapia , Masculino , Síndrome Cardiorrenal/sangue , Pessoa de Meia-Idade , Inflamação/sangue , Idoso , Trombose/sangue , Trombose/etiologia , AdultoRESUMO
Prognostication in acute pulmonary embolism (PE) requires reliable markers. While cellular indices such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII) appear promising, their utility in PE prognostication needs further exploration. We utilized data from the RIETE registry and the Loyola University Medical Center (LUMC) to assess the prognostic value of NLR, PLR, and SII in acute PE, using logistic regression models. The primary outcome was 30-day all-cause mortality. We compared their prognostic value versus the simplified Pulmonary Embolism Severity Index (sPESI) alone. We included 10 085 patients from RIETE and 700 from the LUMC. Thirty-day mortality rates were 4.6% and 8.3%, respectively. On multivariable analysis, an elevated NLR (>7.0) was associated with increased mortality (adjusted odds ratio [aOR]: 3.46; 95% CI: 2.60-4.60), outperforming the PLR > 220 (aOR: 2.36; 95% CI: 1.77-3.13), and SII > 1600 (aOR: 2.52; 95% CI: 1.90-3.33). The c-statistic for NLR in patients with low-risk PE was 0.78 (95% CI: 0.69-0.86). Respective numbers were 0.66 (95% CI: 0.63-0.69) and 0.68 (95% CI: 0.59-0.76) for intermediate-risk and high-risk patients. These findings were mirrored in the LUMC cohort. Among 9810 normotensive patients in RIETE, those scoring 0 points in sPESI and with an NLR ≤ 7.0 (35% of the population) displayed superior sensitivity (97.1%; 95% CI: 95.5-98.7) and negative predictive value (99.7%; 95% CI: 99.5-99.8) than sPESI alone (87.1%; 95% CI: 83.9-90.3, and 98.7%; 95% CI: 98.4-99.1, respectively) for 30-day mortality. The NLR is a significant prognostic marker for 30-day mortality in PE patients, especially useful to identify patients with very low-risk PE.
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Neutrófilos , Embolia Pulmonar , Humanos , Embolia Pulmonar/sangue , Embolia Pulmonar/mortalidade , Embolia Pulmonar/diagnóstico , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Prognóstico , Linfócitos/patologia , Idoso de 80 Anos ou mais , Contagem de Linfócitos , Plaquetas/patologia , Sistema de Registros , Índice de Gravidade de Doença , Contagem de Plaquetas , Biomarcadores/sangueRESUMO
Several risk stratification systems aid clinicians in classifying pulmonary embolism (PE) severity and prognosis. We compared 2 clinical PE scoring systems, the PESI and sPESI scores, with 2 comorbidity indices, the Charlson Comorbidity Index (CCI) and the val Walraven Elixhauser Comorbidity Index (ECI), to determine the utility of each in predicting mortality and hospital readmission. Information was collected from 436 patients presenting with PE via retrospective chart review. The PESI, sPESI, CCI, and ECI scores were calculated for each patient. Multivariate analysis was used to determine each system's ability to predict in-hospital mortality, 90-day mortality, overall mortality, and all-cause hospital readmission. The impact of various demographic and clinical characteristics of each patient on these outcomes was also assessed. The PESI score was found to be an independent predictor of in-hospital mortality and 90-day mortality. The PESI score and the CCI were able to independently predict overall mortality. None of the 4 risk scores independently predicted hospital readmission. Other factors including hypoalbuminemia, serum BNP, coagulopathy, anemia, and diabetes were associated with increased mortality and readmission at various endpoints. The PESI score was the best tool for predicting mortality at any endpoint. The CCI may have utility in predicting long-term outcomes. Further work is needed to better determine the roles of the CCI and ECI in predicting patient outcomes in PE. The potential prognostic implications of low serum albumin and anemia at the time of PE also warrant further investigation.
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Comorbidade , Mortalidade Hospitalar , Readmissão do Paciente , Embolia Pulmonar , Humanos , Embolia Pulmonar/mortalidade , Readmissão do Paciente/estatística & dados numéricos , Feminino , Masculino , Idoso , Pessoa de Meia-Idade , Estudos Retrospectivos , Doença Aguda , Idoso de 80 Anos ou mais , PrognósticoRESUMO
INTRODUCTION: Andexanet alfa (AA) - zhzo, recombinant coagulation factor Xa, is an approved antidote for oral Xa inhibitors (apixaban and rivaroxaban). Unfractionated heparin (UFH) is commonly used for therapeutic, interventional, and surgical indications. Protamine sulfate (PrSO4) is frequently used to neutralize UFH. This study aimed to investigate the comparative neutralization profiles of AA and PrSO4 for heparins of bovine, ovine, and porcine origin. MATERIALS AND METHODS: The neutralization effect of PrSO4 at 25 µg/ml and AA at 100 µg/ml was studied on an approximate surgical/interventional concentration of heparin by supplementing whole blood with each of the heparins at 25 µg/ml. For the clotting profile (activated partial thromboplastin time: aPTT), amidolytic (anti-Xa and anti-IIa), and thrombin generation assay each of the heparin were supplemented from -10-0.62 µg/ml. RESULTS: In the whole blood ACT studies, all three heparins produced strong anti-coagulant effects (400-450â seconds) compared to saline (130-150â seconds). Both AA and PrSO4 almost fully neutralized the anti-coagulant effects of heparins (140-160â seconds). Both antidotes completely reversed the anticoagulant effects of all three heparins in the aPTT and thrombin generation assay. However, PrSO4 was more effective in neutralizing the anti-Xa, and anti-IIa effects than AA, which only partially neutralized these effects. CONCLUSION: Andexanet alfa at 100 µg/ml effectively neutralizes the therapeutic and surgical/interventional concentrations of heparins in in-vitro settings. While differences in the anti-Xa, and anti-IIa effects between heparins were noted, anti-coagulant effect of these agents in the aPTT assay were comparable. A similar neutralization profile was observed in the ACT and thrombin generation assays by both agents.
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Fator Xa , Antagonistas de Heparina , Heparina , Protaminas , Proteínas Recombinantes , Proteínas Recombinantes/farmacologia , Fator Xa/farmacologia , Bovinos , Ovinos , Suínos , Animais , Anticoagulantes/farmacologia , Heparina/farmacologia , Protaminas/farmacologia , Antagonistas de Heparina/farmacologia , Coagulação Sanguínea/efeitos dos fármacos , Tempo de TrombinaRESUMO
Venous thromboembolism (VTE), including deep venous thrombosis (DVT) and pulmonary embolism (PE), represents a substantial healthcare challenge. Provoked and unprovoked DVT cases carry distinct risks and treatment considerations. Recognizing the limitations of this classification, molecular markers may enhance diagnostic precision and guide anticoagulation therapy duration relying on patient history and risk factors. This preliminary, open-label, prospective cohort study was conducted including 15 patients (10 provoked DVT and 5 unprovoked DVT) and a control group of healthy plasmatic subjects. Plasma levels of 9 biomarkers were measured at diagnosis (baseline, day 0, and D0) and after 30 days (day 30-D30). Patient demographics, clinical data, and biomarker concentrations were analyzed. Serum concentrations of D-dimer, von Willebrand factor, C-reactive protein, and Anti-Xa were elevated in DVT groups at D0 compared to controls. No significant differences were observed between the provoked and unprovoked groups on the day of diagnosis and 30 days later. Over 30 days, the provoked group exhibited significant biomarker changes related to temporal assessment. No significant differences were noted in the biomarker profile between provoked and unprovoked DVT groups. This study is indicative of the concept of individualized thrombosis assessment and subsequent treatment for VTE. Larger cohorts are warranted to validate these findings and further define the most appropriate use of the molecular markers.
Assuntos
Embolia Pulmonar , Tromboembolia Venosa , Trombose Venosa , Humanos , Tromboembolia Venosa/tratamento farmacológico , Estudos Prospectivos , Anticoagulantes/uso terapêutico , Embolia Pulmonar/tratamento farmacológico , Fatores de Risco , Biomarcadores , RecidivaRESUMO
BACKGROUND: With the widespread use of direct oral anticoagulants (DOACs), there is an urgent need for a rapid assay to exclude clinically relevant plasma levels. Accurate and rapid determination of DOAC levels would guide medical decision-making to (1) determine the potential contribution of the DOAC to spontaneous or trauma-induced hemorrhage; (2) identify appropriate candidates for reversal, or (3) optimize the timing of urgent surgery or intervention. METHODS AND RESULTS: The DOAC Dipstick test uses a disposable strip to identify factor Xa- or thrombin inhibitors in a urine sample. Based on the results of a systematic literature search followed by an analysis of a simple pooling of five retrieved clinical studies, the test strip has a high sensitivity and an acceptably high negative predictive value when compared with levels measured with liquid chromatography tandem mass spectrometry or calibrated chromogenic assays to reliably exclude plasma DOAC concentrations ≥30 ng/mL. CONCLUSION: Based on these data, a simple algorithm is proposed to enhance medical decision-making in acute care indications useful primarily in hospitals not having readily available quantitative tests and 24/7. This algorithm not only determines DOAC exposure but also differentiates between factor Xa and thrombin inhibitors to better guide clinical management.
Assuntos
Algoritmos , Consenso , Inibidores do Fator Xa , Humanos , Inibidores do Fator Xa/sangue , Inibidores do Fator Xa/uso terapêutico , Administração Oral , Hemorragia , Valor Preditivo dos Testes , Monitoramento de Medicamentos/métodos , Anticoagulantes/uso terapêutico , Anticoagulantes/administração & dosagem , Anticoagulantes/efeitos adversos , Tomada de Decisão Clínica , Antitrombinas , Fitas Reagentes , Espectrometria de Massas em Tandem , Reprodutibilidade dos TestesRESUMO
Venous thromboembolism (VTE), including deep venous thrombosis (DVT) and pulmonary embolism (PE), represents a substantial healthcare challenge. Provoked and unprovoked DVT cases carry distinct risks and treatment considerations. Recognizing the limitations of this classification, molecular markers may enhance diagnostic precision and guide anticoagulation therapy duration relying on patient history and risk factors. This preliminary, open-label, prospective cohort study was conducted including 15 patients (10 provoked DVT and 5 unprovoked DVT) and a control group of healthy plasmatic subjects. Plasma levels of 9 biomarkers were measured at diagnosis (baseline, day 0, and D0) and after 30 days (day 30-D30). Patient demographics, clinical data, and biomarker concentrations were analyzed. Serum concentrations of D-dimer, von Willebrand factor, C-reactive protein, and Anti-Xa were elevated in DVT groups at D0 compared to controls. No significant differences were observed between the provoked and unprovoked groups on the day of diagnosis and 30 days later. Over 30 days, the provoked group exhibited significant biomarker changes related to temporal assessment. No significant differences were noted in the biomarker profile between provoked and unprovoked DVT groups. This study is indicative of the concept of individualized thrombosis assessment and subsequent treatment for VTE. Larger cohorts are warranted to validate these findings and further define the most appropriate use of the molecular markers.
Assuntos
Humanos , Biomarcadores , Tromboembolia Venosa/tratamento farmacológico , Anticoagulantes/uso terapêutico , Embolia Pulmonar/tratamento farmacológico , Recidiva , Estudos Prospectivos , Trombose VenosaRESUMO
Since Charnley introduced acrylic cement to seal metallic hip prostheses in the 1950s, reports of perioperative fatal cardiorespiratory and vascular dysfunctions have been published. Studies on humans and animals have shown neurogenic stimulation and substantial local and systemic activation of coagulation are caused by surgical bone marrow damage and chemical cell destruction by toxic monomeric methyl methacrylate from the implanted cement and other tissue-released substances. Venous blood-borne cell fragments and conjugates of activated cells from the surgical site are sequestered and trapped in the pulmonary microcirculation. A substantial hypercoagulation occurs in the lung circulation. Hypercoagulable blood is passed over to the arterial side and may cause vessel obliteration and organ damage. This process may affect the brain, heart, and kidneys and, through the release of vasoactive substances, introduce hemodynamic imbalances that can lead to fatal outcomes in susceptible populations such as elderly patients with hip fractures. The main underlying pathophysiologic processes leading to these occasionally devastating outcomes are a substantial activation of coagulation and cell destruction caused by the toxic substance released by curing bone cement and several vasoactive substances.
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Cimentos Ósseos , Prótese de Quadril , Animais , Humanos , Idoso , Coagulação Sanguínea , MetilmetacrilatoRESUMO
The burden of atherosclerotic cardiovascular disease contributes to a large proportion of morbidity and mortality, globally. Vaccination against atherosclerosis has been proposed for over 20 years targeting different mediators of atherothrombosis; however, these have not been adequately evaluated in human clinical trials to assess safety and efficacy. Inflammation is a driver of atherosclerosis, but inflammatory mediators are essential components of the immune response. Only pathogenic forms of sTNFR2 are acted upon while preserving the membrane-bound (wild-type) TNFR2 contributions to a non-pathogenic immune response. We hypothesize that the inhibition of sTNRF2 will be more specific and offer long-term treatment options. Here we describe pre-clinical findings of an sTNFR2-targeting peptide vaccine (AtheroVax™) in a mouse model. The multiple pathways to synthesis of the soluble TNFRII receptor (sTNFRII) were identified as sTNFRII(PC), sTNFRII(Δ7), and sTNFRII(Δ7,9). The sTNFRII(Δ7) peptide, NH2-DFALPVEKPLCLQR-COOH is specific to sTNFR2 based on an mRNA splice-variant in which exon 6 is joined to exon 8. The role of sTNFRII(Δ7) as a mediator of prolonged TNFα activity by preventing degradation and clearance was investigated. Inflammation is a critical driver of onset, progression and expansion of atherosclerosis. The TNFα ligand represents a driver of inflammation that is mediated by a splice variant of TNFR2, referred to as sTNFRII(Δ7). The multiple forms of TNFRII, both membrane bound and soluble, are associated with distinctly different phenotypes. sTNFRII(PC) and sTNFRII(Δ7) are not equivalent to etanercept because they lack a clearance mechanism. The unique peptide associated with sTNFRII(Δ7) contains a linear B-cell epitope with amino acids from both exon 6 and exon 8 supporting the vaccine design. Animal studies to evaluate the vaccine are ongoing, and results will be forthcoming. We describe a peptide vaccine targeting sTNFR2 in limiting the progression of atherosclerosis. A therapeutic vaccine limiting the progression of atherosclerosis will greatly contribute to the reduction in morbidity and mortality from cardiovascular disease. It is likely the vaccine will be used in combination with the current standards of care and lifestyle modifications.
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Identifying adherence to direct oral anticoagulants (DOACs) plays a major role in treatment efficacy and safety. The DOAC Dipstick can detect DOACs in urine samples of acutely diseased patients at plasma thresholds of about 30â ng/mL. A prospective observational consecutive cohort study was performed on outpatients taking DOACs. The presence of direct oral factor Xa inhibitors (DXIs) in patient urine samples were independently evaluated by visual interpretation of the DOAC Dipstick pad colors. DOAC plasma concentration was assessed using STA®-Liquid Anti-Xa and STA®-Liquid Anti-IIa chromogenic substrate assays. Positive DOAC Dipstick results were compared with a threshold plasma of DOAC concentration ≥30 ng/mL. Of 120 patients (age 55.4 + 16.1 years, female n = 63), 77 were on rivaroxaban and 43 on apixaban. Plasma concentrations were 129 ± 118 ng/mL for rivaroxaban, and 163 ± 130 ng/mL for apixaban, DOAC Dipstick test has a sensitivity of 97.2% and a positive predictive value of 89.5% at 30â ng/mL. No differences occurred between DXIs. Specificity and negative predictive value could not be determined due to the low number of true negative values. There were no differences in the interpretation of rivaroxaban and apixaban pad colors between observers (Kappa 1.0). Results show that DOAC Dipstick may be a useful tool for identifying DXIs in urine samples in an outpatient setting at a plasma threshold ≥ 30 ng/mL. Further studies should include patients treated with dabigatran, vitamin K antagonists, or other anticoagulants.
Assuntos
Pacientes Ambulatoriais , Rivaroxabana , Adulto , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Administração Oral , Anticoagulantes/uso terapêutico , Compostos Cromogênicos , Estudos de Coortes , Dabigatrana/uso terapêutico , Inibidores do Fator Xa/uso terapêutico , Piridonas/uso terapêutico , Rivaroxabana/uso terapêutico , MasculinoRESUMO
Patients with intermittent claudication have significantly higher levels of inflammatory biomarkers, particularly interleukins, which is also a consequence of exercise limitation. Physical activity, which is one of the preventive measures against atherosclerosis, is associated with a decrease in inflammatory biomarkers. Therefore, in our study, we investigated the effects of revascularization of peripheral arteries in patients with intermittent claudication on functional capacity and levels of inflammatory markers. The study included 26 patients with intermittent claudication who underwent percutaneous transluminal angioplasty (PTA). Before the procedure and 2-4 months after successful revascularization, the ankle-brachial index (ABI), functional capacity using the treadmill test, and the walking impairment questionnaire (WIQ) were determined. Inflammatory biomarkers were also measured before and after procedures. Successful revascularization was associated with an increase in intermittent claudication: 120 (20-315) versus 300 (100-1000â m), P < 0.001. Treadmill testing showed a significant increase in initial and maximal walking distance. After revascularization, ABI increased significantly (0.55 vs 0.82, P < 0.003). Improvement in functional performance was also demonstrated by WIQ. Two to three months after revascularization, some inflammatory biomarkers decreased significantly: fibrinogen, interleukin-6 (IL-6), and interleukin-8 (IL-8). The high-sensitivity C-reactive protein (hsCRP) and tumor necrosis factor-alpha (TNFα) also did not decrease significantly. The levels of some inflammatory markers: IL-6, TNFα, and fibrinogen were significantly related to the improvement in patients' functional capacity. The results of our study show that successful revascularization of the lower limb arteries not only improves the functional capacity of patients with intermittent claudication, but also reduces the systemic inflammatory response and may have a preventive effect on local and concomitant other atherosclerotic diseases.
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Aterosclerose , Hemostáticos , Humanos , Claudicação Intermitente , Interleucina-6 , Fator de Necrose Tumoral alfa , Artérias , Biomarcadores , FibrinogênioRESUMO
Background: In patients at high risk of thromboembolism who were discharged after hospitalisation due to COVID-19, thromboprophylaxis with rivaroxaban 10 mg/day for 35 days significantly improved clinical outcomes, reducing thrombotic events compared with no post-discharge anticoagulation. The present study aimed to estimate the cost-effectiveness of this anticoagulation strategy. Methods: Using the database of the MICHELLE trial, we developed a decision tree to estimate the cost-effectiveness of thromboprophylaxis with rivaroxaban 10 mg/day for 35 days versus no thromboprophylaxis in high-risk post-discharge patients for COVID-19 through an incremental cost-effectiveness analysis. Findings: 318 patients in 14 centres in Brazil were enrolled in the primary MICHELLE trial. The mean age was 57.1 years (SD 15.2), 127 (40%) were women, 191 (60%) were men, and the mean body-mass index was 29.7 kg/m2 (SD 5.6). Rivaroxaban 10 mg per day orally for 35 days after discharge decreased the risk of events defined by the primary efficacy outcome by 67% (relative risk 0.33, 95% CI 0.12-0.90; p = 0.03). The mean cost for thromboprophylaxis with rivaroxaban was $53.37/patient, and no prophylaxis was $34.22/patient, with an incremental cost difference of $19.15. The effectiveness means obtained in the intervention group was 0.1457, while in the control group was 0.1421, determining an incremental QALY difference of 0.0036. The estimated incremental cost-effectiveness ratio (ICER) was $5385.52/QALY. Interpretation: Extended treatment with Rivaroxaban as thromboprophylaxis after hospital discharge for high-risk patients with COVID-19 is a cost-effective treatment option. Funding: Modest funding was provided by Science Valley Research Institute, São Paulo, Brazil.
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En-stage renal disease (ESRD) is a growing public health problem. The atherosclerotic cardiovascular complications are the leading causes of mortality and morbidity in the ESRD. In this study, we sought to quantify the levels of thrombo-inflammatory biomarkers in an ESRD patients in comparison to healthy controls to determine their relevance in thrombo-inflammation and adverse outcomes. The levels of D-Dimer, C-reactive protein (CRP), plasminogen activator inhibitor 1 (PAI-1) antigen, functional PAI-1, thrombin activatable fibrinolysis inhibitor, tissue plasminogen activator, von Willebrand factor, and anti-PF4 IgG and microparticle (MP) activity were quantified by using commercially available ELISA immunoassays for each of the ESRD (n = 73) and control plasma samples (n = 10). The levels of endogenous glycosaminoglycans (GAGs) were quantified by utilizing a Heparin Red Probe (Redprobes UG, Germany). The collected data were analyzed to demonstrate the relationship between various parameters. All the tested biomarkers were increased in ESRD patients in comparison to healthy controls (p < 0.05). These biomarkers have shown significant correlations within each other except for anti-PF4 Ig G and MPs. The CRP levels were significantly higher in patients who had coronary artery disease (CAD) (p < 0.05), but there was no significant difference in other biomarkers according to the cardiovascular outcomes. In the multivariate analysis, the CRP (odds ratio: 1.19; 95% confidence interval: 1.01-1.41; p: 0.03) value was an independent predictor of CAD. In this study, we demonstrated increased levels of 10 different biomarkers in ESRD patients. The CRP levels can be a good predictor of CAD in ESRD patients.
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Doença da Artéria Coronariana , Falência Renal Crônica , Humanos , Inibidor 1 de Ativador de Plasminogênio , Ativador de Plasminogênio Tecidual , Glicosaminoglicanos , Falência Renal Crônica/complicações , Biomarcadores , Proteína C-Reativa/análiseRESUMO
Heparin is a commonly used anticoagulant drug, derived from the tissues of animals including pigs, cows, and sheep. Measuring heparin concentration in plasma is challenging due to its complex molecular structure. Existing methods rely on measuring heparin's anticoagulant activity, which provides pharmacodynamic (PD) data but not pharmacokinetic (PK) data, measuring concentration over time. To overcome this limitation, we used liquid chromatography-mass spectrometry (LC-MS) and the multiple reaction monitoring (MRM) method to directly measure heparin's concentration in non-human primates after administering porcine, bovine, and ovine heparin. A protocol was developed to enable an MRM method for application to small plasma volumes without purification. The PK data obtained from LC-MS are then compared with the data obtained using the Heparin Red assay and the PD data determined using biochemical clinical assays. Results showed that LC-MS and Heparin Red assay measurements closely correlated with unfractionated heparin's biological activities, supporting the use of mass spectra and dye-binding assays to determine heparin levels in plasma. This study builds a way for the measurement of heparin concentration in plasma, which could lead to an improved understanding of heparin's metabolism and dosing safety.
Assuntos
Anticoagulantes , Heparina , Feminino , Animais , Bovinos , Ovinos , Suínos , Heparina/química , Anticoagulantes/farmacologia , Anticoagulantes/química , Primatas/metabolismo , Cromatografia Líquida , Espectrometria de MassasRESUMO
BACKGROUND: Acute pulmonary embolism (PE) is a heterogeneous disease process with variable presentation and outcomes. The endogenous fibrinolytic system is a complex framework of regulatory pathways that maintains homeostasis by dissolving overabundant thrombi. We sought to investigate phenotypic profiles of the endogenous fibrinolytic system among patients presenting with acute PE and their impact on mortality. METHODS: We enrolled all consecutive patients with acute PE in our institutional Pulmonary Embolism Response Team registry. We collected blood samples at the time of PE diagnosis and analyzed concentrations of plasminogen activator inhibitor 1 (PAI-1), thrombin-activatable fibrinolysis inhibitor (TAFI), and alpha-2-antiplasmin (A2A). We assessed the association of concentration of fibrinolytic inhibitors and 1-year all-cause mortality and various echocardiographic markers of right ventricular (RV) dysfunction. RESULTS: There is significant variability of PAI-1, A2A, and TAFI concentrations across the spectrum of PE risk profiles with high PAI-1, low TAFI, and low A2A (herein referred to as a high-risk biomarker profile) correlating with worse PE severity. High-risk biomarker profile correlated with high-risk echocardiographic features of RV dysfunction, including increased RV/left ventricular (LV) ratio, low tricuspid annular plane systolic excursion, and low right ventricular outflow tract velocity time integral. Higher-risk biomarker profile was able to discriminate and independently identify patients at high risk of all-cause mortality (Group 2 HR 6 95% CI 1.3-27.8, Group 3 HR 12, 95% CI 1.7-86). CONCLUSIONS: Further studies are needed to assess the exact pathophysiological link between fibrinolytic status and poor outcome after acute PE and to ascertain the impact of anti-inhibitors of the fibrinolytic system on response to therapy and outcomes after acute PE.