RESUMO
We conducted a study to assess the effect of rosuvastatin use on fibrinolysis in patients with previous venous thromboembolism (VTE). This was a post hoc analysis within the STAtins Reduce Thrombophilia (START) study (NCT01613794). Plasma fibrinolytic potential, fibrinogen, plasmin inhibitor, plasminogen activator inhibitor-1 (PAI-1) and thrombin-activatable fibrinolysis inhibitor (TAFI) were measured before and after four weeks of rosuvastatin or no treatment in participants with prior confirmed VTE, after ending anticoagulant therapy. In the non-rosuvastatin group (n = 121), plasma fibrinolytic potential and individual fibrinolysis parameters did not change at the end of the study versus the baseline, whereas in the rosuvastatin group (n = 126), plasma fibrinolytic potential increased: the mean clot lysis time decreased by 8·75 min (95% CI -13·8 to -3·72), and plasmin inhibitor levels and TAFI activity were lower at the end of the study (-0·05 U/ml; 95% CI -0·07 to -0·02 and -4·77%; 95% CI -6·81 to -2·73, respectively). PAI-1 levels did not change and fibrinogen levels were 0·17 g/l (95% CI 0·04-0·29) higher. In participants with prior VTE, rosuvastatin use led to an increased fibrinolytic potential compared with non-statin use. Our findings support the need for further studies on the possible role for statins in the secondary prevention of VTE.
Assuntos
Fibrinólise/efeitos dos fármacos , Rosuvastatina Cálcica/administração & dosagem , Trombofilia/sangue , Trombofilia/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antifibrinolíticos/sangue , Biomarcadores/sangue , Carboxipeptidase B2/sangue , Feminino , Fibrinogênio/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Inibidor 1 de Ativador de Plasminogênio/sangueRESUMO
BACKGROUND: D-dimers are generated during endogenous fibrinolysis of a blood clot and have a central role in diagnostic algorithms to rule out venous thromboembolism. HMG-CoA reductase inhibitors, more commonly called statins, are known to have effects independent of LDL-cholesterol lowering, including antithrombotic properties. An effect of statins on D-dimer levels has been reported in a prior systematic review and meta-analysis, but methodological shortcomings might have led to an overestimated effect. To re-evaluate the association between statins and D-dimer levels, we systematically reviewed all published articles on the influence of statins on D-dimer levels and conducted a novel meta-analysis (PROSPERO registration number CRD42017058932). MATERIALS AND METHODS: We electronically searched EMBASE, Medline Epub, Cochrane, Web of Science and Google Scholar (100 top relevance) (date of last search: 5 October 2017). We included randomized controlled trials, cohort studies and cross-sectional studies. Two reviewers independently screened all articles retrieved and extracted data on study and patient characteristics, study quality and D-dimer levels. RESULTS: Study-level meta-analysis involving 18,052 study participants showed lower D-dimer levels in those receiving statin treatment than controls (SMD: -0.165, 95% CI -0.234; -0.096, P = <0.001). Sensitivity analyses and additional analyses on treatment duration (<12 weeks vs ≥12 weeks) and type of statin (lipophilic or hydrophilic) did not modify this overall result. CONCLUSION: This meta-analysis suggests an association between use of statins and reduction of D-dimer levels, independent of treatment duration and type of statin used. This effect is small but robust, and should be interpreted with caution.
Assuntos
Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Tromboembolia Venosa/diagnóstico , LDL-Colesterol/sangue , Estudos de Coortes , Estudos Transversais , Humanos , Metanálise como Assunto , Viés de PublicaçãoRESUMO
AIMS: D-dimer is a product of fibrinolysis. In clinical practice, D-dimer levels are commonly used to rule out venous thromboembolism. Antiplatelet drugs may influence D-dimer levels, potentially affecting the accuracy of this diagnostic tool. To evaluate the effect of antiplatelet drugs on D-dimer levels, we performed a systematic review and meta-analysis of all published articles on this topic (PROSPERO registration number CRD42017058932). METHODS AND RESULTS: We electronically searched EMBASE, MEDLINE Epub, Cochrane, Web of Science, and Google Scholar (100 top relevance) (last search on October 5, 2017). We included randomized controlled trials, cohort studies, and cross-sectional studies conducted in humans, with a drug exposure time of at least 7 days. Two reviewers independently selected eligible articles and extracted the data. Five controlled trials, 7 cohort studies, and 5 cross-sectional studies were finally included. Meta-analysis involving all 1117 participants showed no change in dimer levels (standardized mean difference: -0.015, 95% confidence interval, 0.182-0.151, P = 0.855). CONCLUSIONS: In conclusion, antiplatelet drugs do not seem to influence D-dimer levels.
Assuntos
Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Fibrinólise/efeitos dos fármacos , Inibidores da Agregação Plaquetária/uso terapêutico , Tromboembolia Venosa/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Análise Química do Sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Tromboembolia Venosa/sangue , Adulto JovemRESUMO
BACKGROUND: Validated diagnostic algorithms in patients with suspected pulmonary embolism are often not used correctly or only benefit subgroups of patients, leading to overuse of computed tomography pulmonary angiography (CTPA). The YEARS clinical decision rule that incorporates differential D-dimer cutoff values at presentation, has been developed to be fast, to be compatible with clinical practice, and to reduce the number of CTPA investigations in all age groups. We aimed to prospectively evaluate this novel and simplified diagnostic algorithm for suspected acute pulmonary embolism. METHODS: We did a prospective, multicentre, cohort study in 12 hospitals in the Netherlands, including consecutive patients with suspected pulmonary embolism between Oct 5, 2013, to July 9, 2015. Patients were managed by simultaneous assessment of the YEARS clinical decision rule, consisting of three items (clinical signs of deep vein thrombosis, haemoptysis, and whether pulmonary embolism is the most likely diagnosis), and D-dimer concentrations. In patients without YEARS items and D-dimer less than 1000 ng/mL, or in patients with one or more YEARS items and D-dimer less than 500 ng/mL, pulmonary embolism was considered excluded. All other patients had CTPA. The primary outcome was the number of independently adjudicated events of venous thromboembolism during 3 months of follow-up after pulmonary embolism was excluded, and the secondary outcome was the number of required CTPA compared with the Wells' diagnostic algorithm. For the primary outcome regarding the safety of the diagnostic strategy, we used a per-protocol approach. For the secondary outcome regarding the efficiency of the diagnostic strategy, we used an intention-to-diagnose approach. This trial is registered with the Netherlands Trial Registry, number NTR4193. FINDINGS: 3616 consecutive patients with clinically suspected pulmonary embolism were screened, of whom 151 (4%) were excluded. The remaining 3465 patients were assessed of whom 456 (13%) were diagnosed with pulmonary embolism at baseline. Of the 2946 patients (85%) in whom pulmonary embolism was ruled out at baseline and remained untreated, 18 patients were diagnosed with symptomatic venous thromboembolism during 3-month follow-up (0·61%, 95% CI 0·36-0·96) of whom six had fatal pulmonary embolism (0·20%, 0·07-0·44). CTPA was not indicated in 1651 (48%) patients with the YEARS algorithm compared with 1174 (34%) patients, if Wells' rule and fixed D-dimer threshold of less than 500 ng/mL would have been applied, a difference of 14% (95% CI 12-16). INTERPRETATION: In our study pulmonary embolism was safely excluded by the YEARS diagnostic algorithm in patients with suspected pulmonary embolism. The main advantage of the YEARS algorithm in our patients is the absolute 14% decrease of CTPA examinations in all ages and across several relevant subgroups. FUNDING: This study was supported by unrestricted grants from the participating hospitals.
Assuntos
Embolia Pulmonar/diagnóstico , Idoso , Algoritmos , Biomarcadores/metabolismo , Angiografia por Tomografia Computadorizada/estatística & dados numéricos , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Embolia Pulmonar/terapia , Procedimentos Desnecessários/estatística & dados numéricos , Tromboembolia Venosa/etiologiaRESUMO
BACKGROUND: Acute pulmonary embolism may be ruled out by combining nonhigh clinical probability and a normal D-dimer level. Both antiplatelet drugs and HMG-CoA reductase inhibitors (statins) have been associated with effects on thrombus formation, potentially influencing D-dimer levels in this setting, leading to a higher rate of false-negative tests. Therefore, we determined whether D-dimer levels in patients with suspected pulmonary embolism are affected by concomitant use of antiplatelet drugs and/or statins and evaluated whether the effect of antiplatelet drugs or statins might affect diagnostic accuracy. MATERIALS AND METHODS: We performed a posthoc analysis in the YEARS diagnostic study, comparing age- and sex-adjusted D-dimer levels among users of antiplatelet drugs, statins and nonusers. We then reclassified patients within the YEARS algorithm by developing a model in which we adjusted D-dimer cut-offs for statin use and evaluated diagnostic accuracy. RESULTS: We included 156 statins users, 147 antiplatelet drugs users and 726 nonusers of either drugs, all with suspected pulmonary embolism. Use of antiplatelet drugs did not have a significant effect, whereas statin use was associated with 15% decrease in D-dimer levels (95% CI, -28% to -0.6%). An algorithm with lower D-dimer thresholds in statin users yielded lower specificity (0.42 compared to 0.33) with no difference in false-negative tests. CONCLUSIONS: We conclude that use of statins but not of antiplatelet agents is associated with a modest decrease in D-dimer levels. Adjusting D-dimer cut-offs for statin use did, however, not result in a safer diagnostic strategy in our cohort.
Assuntos
Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Inibidores da Agregação Plaquetária/farmacologia , Embolia Pulmonar/diagnóstico , Idoso , Algoritmos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Tromboembolia Venosa/diagnósticoRESUMO
BACKGROUND: Since data on the safety and effectiveness of home telemonitoring and oxygen therapy started directly after Emergency Department (ED) assessment in COVID-19 patients are sparse but could have many advantages, we evaluated these parameters in this study. METHODS: All COVID-19 patients ≥18 years eligible for receiving home telemonitoring (November 2020-February 2022, Albert Schweitzer hospital, the Netherlands) were included: patients started directly after ED assessment (ED group) or after hospital admission (admission group). Safety (number of ED reassessments and hospital readmissions) and effectiveness (number of phone calls, duration of oxygen usage and home telemonitoring) were described in both groups. RESULTS: 278 patients were included (n = 65 ED group, n = 213 admission group). ED group: 23.8% (n = 15) was reassessed, 15.9% (n = 10) was admitted and 7.7% (n = 5) ICU admitted. Admission group: 15.8% (n = 37) was reassessed, 6.5% (n = 14) was readmitted and 2.4% (n = 5) ICU (re)admitted. Ten patients died, of whom 7 due to COVID-19 (1 in ED group; 6 in the admission group). ED group: median duration of oxygen therapy was 9 (IQR 7-13) days; the total duration of home telemonitoring was 14 (IQR 9-18) days. Admission group: duration of oxygen therapy was 10 (IQR 6-16) days; total duration of home telemonitoring was 14 (IQR 10-20) days. CONCLUSION: it appears to be safe to start home telemonitoring and oxygen therapy directly after ED assessment.
RESUMO
INTRODUCTION: The aim of this study was to determine the efficacy of early tocilizumab treatment for hospitalized patients with COVID-19 disease. METHODS: Open-label randomized phase II clinical trial investigating tocilizumab in patients with proven COVID-19 admitted to the general ward and in need of supplemental oxygen. The primary endpoint of the study was 30-day mortality with a prespecified 2-sided significance level of α = 0.10. A post-hoc analysis was performed for a combined endpoint of mechanical ventilation or death at 30 days. Secondary objectives included comparing the duration of hospital stay, ICU admittance and duration of ICU stay and the duration of mechanical ventilation. RESULTS: A total of 354 patients (67% men; median age 66 years) were enrolled of whom 88% received dexamethasone. Thirty-day mortality was 19% (95% CI 14%-26%) in the standard arm versus 12% (95% CI: 8%-18%) in the tocilizumab arm, hazard ratio (HR) = 0.62 (90% CI 0.39-0.98; p = 0.086). 17% of patients were admitted to the ICU in each arm (p = 0.89). The median stay in the ICU was 14 days (IQR 9-28) in the standard arm versus 9 days (IQR 5-14) in the tocilizumab arm (p = 0.014). Mechanical ventilation or death at thirty days was 31% (95% CI 24%-38%) in the standard arm versus 21% (95% CI 16%-28%) in the tocilizumab arm, HR = 0.65 (95% CI 0.42-0.98; p = 0.042). CONCLUSIONS: This randomized phase II study supports efficacy for tocilizumab when given early in the disease course in hospitalized patients who need oxygen support, especially when concomitantly treated with dexamethasone. TRIAL REGISTRATION: https://www.trialregister.nl/trial/8504.
Assuntos
Tratamento Farmacológico da COVID-19 , Idoso , Anticorpos Monoclonais Humanizados , Dexametasona/uso terapêutico , Feminino , Humanos , Masculino , Oxigênio , Respiração Artificial , SARS-CoV-2 , Resultado do TratamentoRESUMO
Statins are generally believed to have cardiovascular protective effects independent of low-density lipoprotein-cholesterol (LDL-C) lowering, such as antithrombotic effects characterized by a decrease in D-dimer levels. For the recently introduced Proprotein convertase subtilisin/kexin 9 (PCSK9) inhibitors antithrombotic effects are yet unknown. We determined the effect of starting PCSK9 inhibitors on D-dimer and fibrinogen levels as most robust markers for thrombogenicity in statin-intolerant patients with familial hypercholesterolemia. We determined D-dimer and fibrinogen levels before and after start of evolocumab (n = 19) or alirocumab (n = 11). Baseline median D-dimer levels were 0.34 mg/L (IQR 0.24-0.59 mg/L) and baseline median fibrinogen levels 3.2 g/L (IQR 2.88-3.63 g/L). At follow-up D-dimer levels (median 0.31 mg/L (IQR 0.25-0.59 mg/L); p = 0.37), and fibrinogen levels (median 3.4 g/L (IQR 2.98-3.62 g/L); p = 0.38) did not change significantly. We therefore conclude PCSK9 inhibitors do not seem to have a profound antithrombotic effect, although a more subtle effect can not been excluded.
Assuntos
Anticorpos Monoclonais/farmacologia , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Fibrinogênio/análise , Fibrinolíticos/farmacologia , Hiperlipoproteinemia Tipo II/tratamento farmacológico , Inibidores de PCSK9 , Idoso , Anticorpos Monoclonais Humanizados , Feminino , Humanos , Hiperlipoproteinemia Tipo II/sangue , Masculino , Pessoa de Meia-IdadeRESUMO
A 47-year-old woman with a history of ulcerative colitis and rheumatoid arthritis presented with a large ulcer with an erythematous halo of the right lower leg. The clinical course and the histopathological results were indicative of pyoderma gangrenosum.
Assuntos
Úlcera da Perna/diagnóstico , Pioderma Gangrenoso/diagnóstico , Diagnóstico Diferencial , Feminino , Humanos , Úlcera da Perna/patologia , Pessoa de Meia-Idade , Pioderma Gangrenoso/patologiaRESUMO
BACKGROUND: Depression has a strong genetic component but candidate gene studies conducted to date have not shown consistent associations. METHODS: We conducted a genome-wide parametric and nonparametric linkage analysis in a large-scale family-based study including 115 individuals with depression who were identified based on the Hospital Anxiety Depression Scale, Center for Epidemiologic Studies Depression Rating Scale, or use of antidepressive medication. Further, we investigated the most promising chromosomal regions found in the genome-wide linkage analysis with an association analysis in 734 individuals in the family-based study and 2373 individuals in the population-based study. RESULTS: Our study demonstrated evidence for significant linkage of depression to chromosome 2p16.1-15 (logarithm of odds [LOD] = 5.13; parametric analysis) and suggestive evidence for linkage in nonparametric analysis to chromosome 5p15.33 (LOD = 2.14), 11q25 (LOD = 2.27), and 19p13.3 (LOD = 2.66). The subsequent association analysis in the family-based study showed region-wide significant association in intron 1 of the OPCML gene on chromosome 11q25 (empirical p value = .04). The association analysis in the population-based study did not show any region-wide significant association, yet showed suggestive association in intron 1 of the APLP2 gene on chromosome 11q25. CONCLUSIONS: Our linkage and association studies suggest a locus for depression on chromosomes 2p16.1-15 and 11q25. The linkage to chromosome 11q25 may be, in part, explained by the OPCML or the APLP2 gene. Further, there is evidence for a role of the GNG7 gene (chromosome 19p13.3).