RESUMO
It is uncertain whether antiphospholipid antibodies (APAs) increase the risk of recurrence after a first unprovoked venous thromboembolism (VTE). We tested for anticardiolipin antibodies, anti-ß2 glycoprotein 1 antibodies, and lupus anticoagulant on 2 occasions â¼6 months apart in 307 patients with a first unprovoked VTE who were part of a prospective cohort study. We then determined if APAs were associated with recurrent thrombosis in the 290 patients who stopped anticoagulant therapy in response to negative D-dimer results. Compared with those without an APA, the hazard ratios for recurrent VTE were 1.8 (95% confidence interval [CI], 0.9-3.7; P = .09) in the 25.9% of patients with an APA on ≥1 occasions, 2.7 (95% CI, 1.1-.7; P = .03) in the 9.0% of patients with the same APA on 2 occasions, and 4.5 (95% CI, 1.5-13.0; P = .006) in the 3.8% of patients with 2 or 3 different APA types on either the same or different occasions. There was no association between having an APA and D-dimer levels. We conclude that having the same type of APA on 2 occasions or having >1 type of APA on the same or different occasions is associated with recurrent thrombosis in patients with a first unprovoked VTE who stop anticoagulant therapy in response to negative D-dimer tests. APA and D-dimer levels seem to be independent predictors of recurrence in patients with an unprovoked VTE. This trial was registered at www.clinicaltrials.gov as #NCT00720915.
Assuntos
Anticorpos Antifosfolipídeos/imunologia , Tromboembolia Venosa/etiologia , Adolescente , Adulto , Idoso , Autoanticorpos/imunologia , Coagulação Sanguínea , Testes de Coagulação Sanguínea , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio , Humanos , Imunoglobulina G/imunologia , Imunoglobulina M/imunologia , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Tromboembolia Venosa/sangue , Tromboembolia Venosa/diagnóstico , Adulto JovemRESUMO
OBJECTIVES: An increased rate of platelet production is a possible cause of reduced antithrombotic response to once-daily aspirin. Markers of immature platelets (IPs), such as immature platelet count (IPC), immature platelet fraction (IPF), and mean platelet volume (MPV) might be useful for identifying patients who have an increase in their rate of platelet production. However, their potential as markers of platelet production has not been rigorously evaluated. We aimed to investigate the utility of the IPC, IPF, and MPV as surrogates for increased platelet production using coronary artery bypass grafting (CABG) as a model of enhanced thrombopoiesis. METHODS: Daily changes in platelet count, IPC, IPF, and MPV were followed in 45 patients undergoing CABG. RESULTS: The rise in IP markers preceded that in the platelet count. IPC (16% per day increase from nadir) but not IPF or MPV showed a significant and sustained rise, which paralleled the pattern observed with platelet count (18% per day increase from nadir). CONCLUSIONS: Of the 3 markers, IPC was the most promising as surrogates for platelet production. Future studies should evaluate the utility of the IPC to identify patients with cardiovascular disease with reduced response to aspirin who might benefit from twice-daily aspirin.
Assuntos
Plaquetas/patologia , Ponte de Artéria Coronária , Contagem de Plaquetas , Trombopoese , Idoso , Feminino , Humanos , Masculino , Volume Plaquetário Médio , Pessoa de Meia-Idade , Período Pós-Operatório , Fatores de Risco , Fatores de TempoRESUMO
Canadian guidelines recommend non vitamin K antagonists (NOACs) in preference to vitamin K antagonists (VKAs) for stroke prevention in patients with atrial fibrillation (AF), but NOACs are more expensive than VKAs. Canada has a universal healthcare system that covers the cost of NOACs for select patient groups. Ability to pay for NOACs may influence their use. We reviewed medical charts of Hamilton General Hospital outpatients under the age of 65 with a new diagnosis of AF who were referred for initiation of OAC therapy. We contacted these patients by phone and asked them to complete a questionnaire regarding their OAC choice, economic factors that may have influenced this choice (income, insurance) and the financial burden of OAC therapy. We included 110 patients, mean age 56 years, and 26.4% females. NOAC users had a higher median neighborhood income than VKA users (p = 0.0144, n = 110). 73 patients responded to the questionnaire. NOAC users reported higher annual household income (p = 0.0038, n = 73). Patients with private insurance were more likely to use NOACs than those without insurance (p = 0.0496, n = 73). The cost of NOACs and ability to pay is a determinant of their use Ontario patients under the age of 65. This two tiered provision of care appears to contradict the values of Canada's universal healthcare system.
Assuntos
Fibrilação Atrial/tratamento farmacológico , Fibrinolíticos/economia , Vitamina K/antagonistas & inibidores , Fibrilação Atrial/economia , Efeitos Psicossociais da Doença , Feminino , Fibrinolíticos/uso terapêutico , Gastos em Saúde , Humanos , Renda , Seguro Saúde , Masculino , Pessoa de Meia-Idade , Ontário , Acidente Vascular Cerebral/prevenção & controle , Inquéritos e QuestionáriosRESUMO
BACKGROUND: The media serves as an important link between medical research, as reported in scholarly sources, and the public and has the potential to act as a powerful tool to improve public health. However, concerns about the reliability of health research reports have been raised. Tools to monitor the quality of health research reporting in the media are needed to identify areas of weakness in health research reporting and to subsequently work towards the efficient use of the lay media as a public health tool through which the public's health behaviors can be improved. METHODS: We developed the Quality Index for health-related Media Reports (QIMR) as a tool to monitor the quality of health research reports in the lay media. The tool was developed according to themes generated from interviews with health journalists and researchers. Item and domain characteristics and scale reliability were assessed. The scale was correlated with a global quality assessment score and media report word count to provide evidence towards its construct validity. RESULTS: The items and domains of the QIMR demonstrated acceptable validity and reliability. Items from the 'validity' domain were negatively skewed, suggesting possible floor effect. These items were not eliminated due to acceptable content and face validity. QIMR total scores produced a strong correlation with raters' global assessment and a moderate correlation with media report word count, providing evidence towards the construct validity of the instrument. CONCLUSIONS: The results of this investigation indicate that QIMR can adequately measure the quality of health research reports, with acceptable reliability and validity.
Assuntos
Pesquisa Biomédica/métodos , Psicometria/instrumentação , Qualidade da Assistência à Saúde/normas , Relatório de Pesquisa/normas , Humanos , Reprodutibilidade dos Testes , Inquéritos e QuestionáriosAssuntos
Tiazóis , Tromboembolia Venosa , Administração Oral , Anticoagulantes , Inibidores do Fator Xa , Humanos , Neoplasias , Piridinas , Resultado do TratamentoRESUMO
The P2Y12 inhibitors, clopidogrel, prasugrel, and ticagrelor, are administered in fixed doses without laboratory monitoring. Randomized trials in acute coronary syndrome have shown that prasugrel and ticagrelor are more effective than standard-dose clopidogrel. Nonetheless, standard-dose clopidogrel remains widely used because it causes less bleeding and is less expensive. Patients treated with standard-dose clopidogrel have substantial variability in platelet inhibition, which is partly explained by genetic polymorphisms encoding CYP2C19, the hepatic enzyme involved in biotransformation of clopidogrel to its active metabolite. Some advocate tailoring P2Y12 inhibitor therapy according to the results of routine laboratory testing. Although there is good evidence for analytic, biological, and clinical validity of several phenotypic and genotypic biomarkers, the benefit of a management strategy that incorporates routine biomarker testing over standard of care without such testing remains unproven. Appropriately designed, adequately powered trials are needed but face the challenges of feasibility, cost, and the progressive switch from clopidogrel to prasugrel or ticagrelor.
Assuntos
Síndrome Coronariana Aguda , Hidrocarboneto de Aril Hidroxilases , Testes Genéticos , Polimorfismo Genético , Antagonistas do Receptor Purinérgico P2Y , Ticlopidina/análogos & derivados , Síndrome Coronariana Aguda/tratamento farmacológico , Síndrome Coronariana Aguda/enzimologia , Síndrome Coronariana Aguda/genética , Adenosina/análogos & derivados , Adenosina/farmacocinética , Adenosina/uso terapêutico , Hidrocarboneto de Aril Hidroxilases/genética , Hidrocarboneto de Aril Hidroxilases/metabolismo , Clopidogrel , Citocromo P-450 CYP2C19 , Substituição de Medicamentos , Humanos , Piperazinas/farmacocinética , Piperazinas/uso terapêutico , Cloridrato de Prasugrel , Antagonistas do Receptor Purinérgico P2Y/farmacocinética , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Tiofenos/farmacocinética , Tiofenos/uso terapêutico , Ticagrelor , Ticlopidina/farmacocinética , Ticlopidina/uso terapêuticoRESUMO
When counseling first-degree relatives of patients with venous thromboembolism (VTE), it is important to know whether factors other than thrombophilia influence their risk for thrombosis. We assessed the risk for VTE in 915 first-degree relatives of patients with provoked VTE, compared this with the risk in 1752 first-degree relatives of patients with unprovoked VTE, and then combined data from the 2 groups of relatives to identify predictors of thrombosis. There had been 123 VTEs in 2617 first-degree relatives (0.12 per 100 person-years). The risk for VTE in first-degree relatives was higher if the index cases had an unprovoked compared with a provoked VTE (odds ratio [OR], 2.38; 95% confidence interval [CI], 1.43-3.85), if the index case was younger (OR, 0.97 per year older; 95% CI, 0.96-0.99), and if an additional family member had VTE (OR, 2.71; 95% CI, 2.22-3.31). Among first-degree relatives of an index case with factor V Leiden or the prothrombin 20210A gene variant, the presence of these abnormalities also predicted thrombosis (OR, 4.42; 95% CI, 1.35-14.38). We conclude that thrombosis at a young age and unprovoked VTE predict VTE in first-degree relatives, and that the influence of these 2 factors is additive.
Assuntos
Família , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Fator V/genética , Feminino , Predisposição Genética para Doença , Variação Genética , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Razão de Chances , Prognóstico , Protrombina/genética , Fatores de Risco , Tromboembolia Venosa/epidemiologiaRESUMO
The post-thrombotic syndrome (PTS) is a frequent, potentially disabling complication of deep vein thrombosis (DVT) that reduces quality of life and is costly. Clinical manifestations include symptoms and signs such as leg pain and heaviness, edema, redness, telangiectasia, new varicose veins, hyperpigmentation, skin thickening and in severe cases, leg ulcers. The best way to prevent PTS is to prevent DVT with pharmacologic or mechanical thromboprophylaxis used in high risk patients and settings. In patients whose DVT is treated with a vitamin K antagonist, subtherapeutic INRs should be avoided. We do not suggest routine use of elastic compression stockings (ECS) after DVT to prevent PTS, but in patients with acute DVT-related leg swelling that is bothersome, a trial of ECS is reasonable. We suggest that selecting patients for catheter-directed thrombolytic techniques be done on a case-by-case basis, with a focus on patients with extensive thrombosis, recent symptoms onset, and low bleeding risk, who are seen at experienced hospital centers. For patients with established PTS, we suggest prescribing 20-30 mm Hg knee-length ECS to be worn daily. If ineffective, a stronger pressure stocking can be tried. We suggest that intermittent compression devices or pneumatic compression sleeve units be tried in patients with moderate-to-severe PTS whose symptoms are inadequately controlled with ECS alone. We suggest that a supervised exercise training program for 6 months or more is reasonable for PTS patients who can tolerate it. We suggest that management of post-thrombotic ulcers should involve a multidisciplinary approach. We briefly discuss upper extremity PTS and PTS in children.
Assuntos
Anticoagulantes/uso terapêutico , Síndrome Pós-Trombótica/diagnóstico , Síndrome Pós-Trombótica/prevenção & controle , Humanos , Guias de Prática Clínica como Assunto , Vitamina K/antagonistas & inibidoresRESUMO
BACKGROUND: Normal D-dimer levels after withdrawal of anticoagulant therapy are associated with a reduced risk for recurrence in patients with unprovoked venous thromboembolism (VTE) and may justify stopping treatment. OBJECTIVE: To determine whether patients with a first unprovoked VTE and negative D-dimer test result who stop anticoagulant therapy have a low risk for recurrence. DESIGN: Prospective management study with blinded outcome assessment. (ClinicalTrials.gov: NCT00720915). SETTING: 13 university-affiliated clinical centers. PATIENTS: 410 adults aged 75 years or younger with a first unprovoked proximal deep venous thrombosis or pulmonary embolism who had completed 3 to 7 months of anticoagulant therapy. INTERVENTION: Anticoagulant therapy was stopped if D-dimer test results were negative and was not restarted if results were still negative after 1 month. MEASUREMENTS: Recurrent VTE during an average follow-up of 2.2 years. RESULTS: In 319 patients (78%) who had 2 negative D-dimer results and did not restart anticoagulant therapy, rates of recurrent VTE were 6.7% (95% CI, 4.8% to 9.0%) per patient-year overall (42 of 319), 9.7% (CI, 6.7% to 13.7%) per patient-year in men (33 of 180), 5.4% (CI, 2.5% to 10.2%) per patient-year in women with VTE not associated with estrogen therapy (9 of 81), and 0.0% (CI, 0.0% to 3.0%) per patient-year in women with VTE associated with estrogen therapy (0 of 58) (P = 0.001 for the 3-group comparison). LIMITATIONS: Imprecision in female subgroups. Results may not be generalizable to different D-dimer assays from the one used in the study. CONCLUSION: The risk for recurrence in patients with a first unprovoked VTE who have negative D-dimer results is not low enough to justify stopping anticoagulant therapy in men but may be low enough to justify stopping therapy in women. PRIMARY FUNDING SOURCE: Canadian Institutes of Health Research.
Assuntos
Anticoagulantes/uso terapêutico , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Embolia Pulmonar/sangue , Embolia Pulmonar/tratamento farmacológico , Tromboembolia Venosa/sangue , Tromboembolia Venosa/tratamento farmacológico , Adulto , Anticoagulantes/efeitos adversos , Causas de Morte , Feminino , Hemorragia/induzido quimicamente , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Masculino , Pessoa de Meia-Idade , Neoplasias/diagnóstico , Inibidores da Agregação Plaquetária/uso terapêutico , Estudos Prospectivos , Recidiva , Fatores de Risco , Fatores Sexuais , Meias de Compressão , Suspensão de TratamentoRESUMO
BACKGROUND: Post-thrombotic syndrome (PTS) is a common and burdensome complication of deep venous thrombosis (DVT). Previous trials suggesting benefit of elastic compression stockings (ECS) to prevent PTS were small, single-centre studies without placebo control. We aimed to assess the efficacy of ECS, compared with placebo stockings, for the prevention of PTS. METHODS: We did a multicentre randomised placebo-controlled trial of active versus placebo ECS used for 2 years to prevent PTS after a first proximal DVT in centres in Canada and the USA. Patients were randomly assigned to study groups with a web-based randomisation system. Patients presenting with a first symptomatic, proximal DVT were potentially eligible to participate. They were excluded if the use of compression stockings was contraindicated, they had an expected lifespan of less than 6 months, geographical inaccessibility precluded return for follow-up visits, they were unable to apply stockings, or they received thrombolytic therapy for the initial treatment of acute DVT. The primary outcome was PTS diagnosed at 6 months or later using Ginsberg's criteria (leg pain and swelling of ≥1 month duration). We used a modified intention to treat Cox regression analysis, supplemented by a prespecified per-protocol analysis of patients who reported frequent use of their allocated treatment. This study is registered with ClinicalTrials.gov, number NCT00143598, and Current Controlled Trials, number ISRCTN71334751. FINDINGS: From 2004 to 2010, 410 patients were randomly assigned to receive active ECS and 396 placebo ECS. The cumulative incidence of PTS was 14·2% in active ECS versus 12·7% in placebo ECS (hazard ratio adjusted for centre 1·13, 95% CI 0·73-1·76; p=0·58). Results were similar in a prespecified per-protocol analysis of patients who reported frequent use of stockings. INTERPRETATION: ECS did not prevent PTS after a first proximal DVT, hence our findings do not support routine wearing of ECS after DVT. FUNDING: Canadian Institutes of Health Research.
Assuntos
Síndrome Pós-Trombótica/prevenção & controle , Meias de Compressão , Adulto , Idoso , Anticoagulantes/uso terapêutico , Canadá/epidemiologia , Terapia Combinada , Método Duplo-Cego , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Síndrome Pós-Trombótica/epidemiologia , Síndrome Pós-Trombótica/etiologia , Recidiva , Fatores de Risco , Índice de Gravidade de Doença , Resultado do Tratamento , Estados Unidos/epidemiologia , Trombose Venosa/tratamento farmacológicoRESUMO
In the last decade, major advances in venous thromboembolism (VTE) prophylaxis in orthopaedic surgery have included the development of new anticoagulants that are poised to replace low molecular weight heparins (LMWHs) and improvements in operative and perioperative care that have likely led to a decline in the rates of symptomatic VTE and mortality independent of anticoagulant use. A systematic review of the literature was performed to identify phase III randomized controlled trials of VTE prevention that compared new anticoagulants (fondaparinux, rivaroxaban, dabigatran, apixaban) with LMWH (enoxaparin) in major elective orthopaedic surgery. Our aims were to obtain best estimates of the rates of patient important events (symptomatic VTE, mortality, and bleeding) in contemporary trials of VTE prevention, and to consider the implications of these contemporary rates for clinical practice and future research. Fourteen studies, which enrolled 40,285 patients, were included in the analyses. The combined median rates (ranges) for all five anticoagulants for symptomatic VTE and mortality to the end of follow-up were 0.99 % (0.15-2.58 %) and 0.26 % (0-0.92 %) respectively, whereas the median rate (range) of clinically important bleeding was 3.44 % (2.25-7.74 %). In contemporary trials of anticoagulants, the rates of symptomatic VTE and mortality are low, but the rates of clinically important post-operative bleeding remain relatively high. Based on these results, we propose that approaches that minimize bleeding without substantially reducing efficacy merit investigation, particularly if improvement in surgical and perioperative care have also resulted in falling baseline patient important VTE rates independent of anticoagulant use.
Assuntos
Anticoagulantes/uso terapêutico , Procedimentos Ortopédicos , Complicações Pós-Operatórias/mortalidade , Complicações Pós-Operatórias/prevenção & controle , Tromboembolia Venosa/mortalidade , Tromboembolia Venosa/prevenção & controle , Anticoagulantes/efeitos adversos , Ensaios Clínicos Fase III como Assunto , Feminino , Humanos , Masculino , Ensaios Clínicos Controlados Aleatórios como Assunto , Tromboembolia Venosa/etiologiaRESUMO
BACKGROUND: D-Dimer testing is sensitive but not specific for diagnosing deep venous thrombosis (DVT). Changing the use of testing and the threshold level for a positive test result on the basis of risk for DVT might improve the tradeoff between sensitivity and specificity and reduce the need for testing. OBJECTIVE: To determine whether using a selective D-dimer testing strategy based on clinical pretest probability (C-PTP) for DVT is safe and reduces diagnostic testing compared with using a single D-dimer threshold for all patients. DESIGN: Randomized, multicenter, controlled trial. Patients were allocated using a central automated system. Ultrasonographers and study adjudicators but not other study personnel were blinded to trial allocation. (ClinicalTrials.gov: NCT00157677) SETTING: 5 Canadian hospitals. PATIENTS: Consecutive symptomatic patients with a first episode of suspected DVT. INTERVENTION: Selective testing (n = 860), defined as D-dimer testing for outpatients with low or moderate C-PTP (DVT excluded at D-dimer levels <1.0 µg/mL [low C-PTP] or <0.5 µg/mL [moderate C-PTP]) and venous ultrasonography without D-dimer testing for outpatients with high C-PTP and inpatients, or uniform testing (n = 863), defined as D-dimer testing for all participants (DVT excluded at D-dimer levels <0.5 µg/mL). MEASUREMENTS: The proportion of patients not diagnosed with DVT during initial testing who had symptomatic venous thromboembolism during 3-month follow-up and the proportion of patients undergoing D-dimer testing and ultrasonography. RESULTS: The incidence of symptomatic venous thromboembolism at 3 months was 0.5% in both study groups (difference, 0.0 percentage point [95% CI, -0.8 to 0.8 percentage points]). Selective testing reduced the proportion of patients who required D-dimer testing by 21.8 percentage points (CI, 19.1 to 24.8 percentage points). It reduced the proportion who required ultrasonography by 7.6 percentage points (CI, 2.9 to 12.2 percentage points) overall and by 21.0 percentage points (CI, 14.2 to 27.6 percentage points) in outpatients with low C-PTP. LIMITATION: Results may not be generalizable to all D-dimer assays or patients with previous DVT, study personnel were not blinded, and the trial was stopped prematurely. CONCLUSION: A selective D-dimer testing strategy seems as safe as and more efficient than having everyone undergo D-dimer testing when diagnosing a first episode of suspected DVT. PRIMARY FUNDING SOURCE: Heart and Stroke Foundation of Ontario.
Assuntos
Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Tromboembolia Venosa/diagnóstico , Trombose Venosa/diagnóstico , Adolescente , Seguimentos , Humanos , Probabilidade , Sensibilidade e Especificidade , Ultrassonografia , Tromboembolia Venosa/sangue , Tromboembolia Venosa/diagnóstico por imagem , Trombose Venosa/sangue , Trombose Venosa/diagnóstico por imagemRESUMO
BACKGROUND: Compression ultrasonography performed serially over a 7-day period is recommended for the diagnosis of deep vein thrombosis in symptomatic pregnant women, but whether this approach is safe is unknown. We evaluated the safety of withholding anticoagulation from pregnant women with suspected deep vein thrombosis following negative serial compression ultrasonography and iliac vein imaging. METHODS: Consecutive pregnant women who presented with suspected deep vein thrombosis underwent compression ultrasonography and Doppler imaging of the iliac vein of the symptomatic leg(s). Women whose initial test results were negative underwent serial testing on 2 occasions over the next 7 days. Women not diagnosed with deep vein thrombosis were followed for a minimum of 3 months for the development of symptomatic deep vein thrombosis or pulmonary embolism. RESULTS: In total, 221 pregnant women presented with suspected deep vein thrombosis. Deep vein thrombosis was diagnosed in 16 (7.2%) women by initial compression ultrasonography and Doppler studies; none were identified as having deep vein thrombosis on serial testing. One patient with normal serial testing had a pulmonary embolism diagnosed 7 weeks later. The overall prevalence of deep vein thrombosis was 7.7% (17/221); of these, 65% (11/17) of cases were isolated to the iliofemoral veins and 12% (2/17) were isolated iliac deep vein thromboses. The incidence of venous thromboembolism during follow-up was 0.49% (95% confidence interval [CI] 0.09%-2.71%). The sensitivity of serial compression ultrasonography with Doppler imaging was 94.1% (95% CI 69.2%-99.7%), the negative predictive value was 99.5% (95% CI 96.9%-100%), and the negative likelihood ratio was 0.068 (95% CI 0.01-0.39). INTERPRETATION: Serial compression ultrasonography with Doppler imaging of the iliac vein performed over a 7-day period excludes deep-vein thrombosis in symptomatic pregnant women.
Assuntos
Anticoagulantes/uso terapêutico , Veia Ilíaca/diagnóstico por imagem , Complicações Cardiovasculares na Gravidez/diagnóstico por imagem , Ultrassonografia Doppler , Ultrassonografia Pré-Natal/métodos , Trombose Venosa/diagnóstico por imagem , Suspensão de Tratamento , Adulto , Algoritmos , Técnicas de Apoio para a Decisão , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Gravidez , Complicações Cardiovasculares na Gravidez/tratamento farmacológico , Estudos Prospectivos , Sensibilidade e Especificidade , Trombose Venosa/tratamento farmacológicoRESUMO
Compared with warfarin, dabigatran is associated with less intracranial hemorrhage, but an increased risk of myocardial infarction. To explore these phenomena, we compared their effects on thrombin generation. Thrombin generation in plasma from 10 patients taking therapeutic doses of warfarin (mean INR 2.6) was compared with that in plasma containing 250 ng/mL dabigatran. Although lag times were similar when thrombin generation was induced by recalcification or with a range of tissue factor concentrations, there was a greater reduction in peak thrombin generation and endogenous thrombin potential in plasma from warfarin-treated patients than in dabigatran-containing plasma. Similar results were obtained when thrombin generation was determined in plasma samples from 18 warfarin or 36 dabigatran treated patients entered into the RE-LY trial. Warfarin suppresses thrombin generation more efficiently than dabigatran. Greater suppression of normal hemostatic mechanisms in the brain and pathological thrombosis at sites of atherosclerotic plaque disruption may explain the higher rate of intracranial bleeding and lower rate of myocardial infarction with warfarin compared with dabigatran.
Assuntos
Benzimidazóis/uso terapêutico , Hemorragias Intracranianas/tratamento farmacológico , Infarto do Miocárdio/tratamento farmacológico , Trombina/antagonistas & inibidores , Varfarina/uso terapêutico , beta-Alanina/análogos & derivados , Anticoagulantes/farmacologia , Anticoagulantes/uso terapêutico , Antitrombinas/farmacologia , Antitrombinas/uso terapêutico , Benzimidazóis/farmacologia , Dabigatrana , Feminino , Humanos , Hemorragias Intracranianas/sangue , Masculino , Infarto do Miocárdio/sangue , Trombina/metabolismo , Varfarina/farmacologia , beta-Alanina/farmacologia , beta-Alanina/uso terapêuticoRESUMO
BACKGROUND: D-dimer testing to rule out deep vein thrombosis is less useful in older patients because of a lower specificity. An age-adjusted D-dimer cut-off value increased the proportion of older patients (>50 years) in whom pulmonary embolism could be excluded. We retrospectively validated the efficacy of this cut-off combined with clinical probability for the exclusion of deep vein thrombosis. DESIGN AND METHODS: Five management study cohorts of 2818 consecutive outpatients with suspected deep vein thrombosis were used. Patients with non-high or unlikely probability of deep vein thrombosis were included in the analysis; four different D-dimer tests were used. The proportion of patients with a normal D-dimer test and the failure rates were calculated using the conventional (500 µg/L) and the age-adjusted D-dimer cut-off (patient's age x 10 µg/L in patients >50 years). RESULTS: In 1672 patients with non-high probability, deep vein thrombosis could be excluded in 850 (51%) patients with the age-adjusted cut-off value versus 707 (42%) patients with the conventional cut-off value. The failure rates were 7 (0.8; 95% confidence interval 0.3-1.7%) for the age-adjusted cut-off value and 5 (0.7%, 0.2-1.6%) for the conventional cut-off value. The absolute increase in patients in whom deep vein thrombosis could be ruled out using the age-adjusted cut-off value was largest in patients >70 years: 19% among patients with non-high probability. CONCLUSIONS: The age-adjusted cut-off of the D-dimer combined with clinical probability greatly increases the proportion of older patients in whom deep vein thrombosis can be safely excluded.
Assuntos
Produtos de Degradação da Fibrina e do Fibrinogênio , Trombose Venosa/diagnóstico , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Valores de Referência , Estudos Retrospectivos , Sensibilidade e Especificidade , Trombose Venosa/sangueRESUMO
RATIONALE: We report a new method to diagnose acute pulmonary embolism (PE) by single photon emission computerized tomography (SPECT) after administration of (99m)Tc-labeled anti-D-dimer (DI-80B3) monoclonal antibody Fab' fragments. This novel technique provides an additional approach to diagnosing PE in patients for whom other methods are nondiagnostic or contraindicated. OBJECTIVES: We performed a prospective, multicenter study to investigate the sensitivity and specificity of (99m)Tc-DI-80B3/SPECT in patients with suspected acute PE. METHODS: Subjects with a moderate to high clinical probability of PE or a positive D-dimer test underwent a PE-protocol contrast-enhanced multidetector thoracic computed tomography (CT) scan as well as (99m)Tc-DI-80B3/SPECT (0.5 mg (99m)Tc-DI-80B3 intravenously followed by a thoracic SPECT 2.5 h later). Separate and independent adjudication committees, blinded to clinical data and other test results, interpreted the (99m)Tc-DI-80B3/SPECT scans (PE detected as foci of abnormally increased (99m)Tc uptake) and the thoracic CT scans using Prospective Investigation of Pulmonary Embolism Diagnosis II criteria. MEASUREMENTS AND MAIN RESULTS: Of the 52 patients who were enrolled and completed both tests, 42 had both evaluable SPECT scans and thoracic CT scans. Using the criterion standard (thoracic CT scan) there were 21 patients with PE and 21 without. (99m)Tc-DI-80B3/SPECT had a sensitivity of 76.2% (95% confidence interval, 52.8-91.8%) and a specificity of 90.5% (95% confidence interval, 69.8-98.8%). Treatment-related serious adverse events did not occur. CONCLUSIONS: (99m)Tc-DI-80B3/SPECT was sensitive and specific for acute PE in subjects with moderate to high clinical probability of PE or a positive D-dimer test. (99m)Tc-DI-80B3/SPECT demonstrated an acceptable safety profile and avoids exposure to contrast.
Assuntos
Anticorpos Monoclonais , Compostos de Organotecnécio , Embolia Pulmonar/diagnóstico por imagem , Compostos Radiofarmacêuticos , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Anticorpos Monoclonais Humanizados , Meios de Contraste , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada Multidetectores/métodos , Variações Dependentes do Observador , Estudos Prospectivos , Intensificação de Imagem Radiográfica/métodos , Sensibilidade e EspecificidadeRESUMO
Background Patients with atrial fibrillation (AF) are frequently treated with apixaban 2.5-mg twice daily (BID) off-label, presumably to reduce the bleeding risk. However, this approach has the potential to increase the risk of ischemic stroke. If a single measurement could reliably identify patients with high drug levels, the increased stroke risk may be mitigated by confining off-label dose reduction to such patients. Objectives This study aimed to determine whether a single high apixaban level is predictive of a similarly high level when the test is repeated in 2 months. Methods In this prospective cohort study of clinic patients receiving apixaban 5-mg BID for AF or venous thromboembolism, peak and trough apixaban levels were measured using the STA-Liquid anti-Xa assay at baseline and 2 months. We calculated the proportions of patients with levels that remained in the upper quintile. Results Of 100 enrolled patients, 82 came for a second visit, 55 of whom were treated with apixaban 5-mg BID. Seven (63.6%, 95% confidence interval [CI]: 35.4-84.8%) and nine (81.8%, 95% CI: 52.3-94.9%) of 11 patients with a baseline trough and peak level in the upper quintile, respectively, had a subsequent level that remained within this range. Only one (9.1%, 95% CI: 1.6-37.7%) patient had a subsequent level that fell just lower than the median. Conclusion The trough and peak levels of apixaban in patients who have a high level on a single occasion, usually remain high when the assay is repeated in 2 months. Accordingly, the finding of a high apixaban level in patients deemed to be at high risk of bleeding, allows physicians contemplating off-label use of the 2.5-mg BID dose to limit its use to selected patients who are less likely to be exposed to an increased risk of thrombosis.
RESUMO
Introduction Dose adjustment based on laboratory monitoring is not routinely recommended for patients treated with rivaroxaban but because an association has been reported between high drug level and bleeding, it would be of interest to know if measuring drug level once could identify patients at risk of bleeding who might benefit from a dose reduction. Objective This study was aimed to investigate the reliability of a single measurement of rivaroxaban level to identify clinic patients with persistently high levels, defined as levels that remained in the upper quintile of drug-level distribution. Methods In this prospective cohort study of 100 patients with atrial fibrillation or venous thromboembolism, peak and trough rivaroxaban levels were measured using the STA-Liquid Anti-Xa assay at baseline and after 2 months. Values of 395.8 and 60.2 ng/mL corresponded to the 80th percentile for peak and trough levels, respectively, and levels above these cut-offs were categorized as high for our analyses. Results Among patients with a peak or trough level in the upper quintile at baseline, only 26.7% (95% confidence interval [CI]: 10.9-52.0%), and 13.3% (95% CI: 2.4-37.9%), respectively, remained above these thresholds. Conclusion Our findings do not support the use of a single rivaroxaban level measurement to identify patients who would benefit from a dose reduction because such an approach is unable to reliably identify patients with high levels.
RESUMO
Until recently, attempts to improve the benefit of aspirin by adding another antithrombotic agent have not resulted in a mortality reduction in patients with chronic symptomatic atherosclerosis. In this population, COMPASS is the only one among six trials to show a significant mortality reduction, thereby providing evidence of a clear net clinical benefit with the combination of low-dose rivaroxaban plus aspirin. In this systematic review, we sought to determine whether the mortality benefit of the combination arm in COMPASS is best explained by greater statistical power or by a more favorable efficacy-safety profile than the other regimens evaluated in patients with chronic symptomatic atherosclerosis.