RESUMO
Glucocorticoid treatment increases venous thromboembolism (VTE) risk. Whether this is due to the medication or the underlying disease, or affects the risk of VTE recurrence, has been difficult to determine. The aim of our present study was to quantify the risk for first and recurrent VTE associated with oral glucocorticoids use, considering the underlying disease. A total of 2547 patients with VTE from the Multiple Environmental and Genetic Assessment of Risk Factors for Venous Thrombosis (MEGA) study were linked to the Dutch Pharmaceutical Statistics register. The risk of first VTE during periods of exposure with oral glucocorticoids was estimated by the self-controlled case series method and that of recurrent VTE was examined in a cohort design. The incidence rate ratio (IRR) of first VTE in the period of glucocorticoid treatment was 3·51 [95% confidence interval (CI) 2·55-4·80]. This IRR was 2·53 (95% CI 1·10-5·72) in the week before treatment started, 5·28 (95% CI 2·89-9·53) in the first 7 days of treatment, remained elevated afterwards and decreased to 1·55 (95% CI 0·85-3·12) after 6 months, as compared to unexposed periods. The hazard ratio for recurrence was 2·72 (95% CI 1·64-4·78) in treatment periods as compared with no treatment. The increased risk of VTE associated with oral glucocorticoid treatment is due to a combined effect of the treatment and the underlying disease, remaining high during the first months of prescription.
Assuntos
Glucocorticoides , Tromboembolia Venosa , Administração Oral , Adolescente , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Seguimentos , Glucocorticoides/administração & dosagem , Glucocorticoides/efeitos adversos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Tromboembolia Venosa/sangue , Tromboembolia Venosa/induzido quimicamente , Tromboembolia Venosa/epidemiologiaRESUMO
OBJECTIVE: This study aimed at evaluating the effect of thrombophilia on the risk of venous thromboembolism (VTE) in patients undergoing any type of orthopedic surgery. BACKGROUND: Patients undergoing orthopedic surgery are at high risk for VTE. Although patients with thrombophilia have an increased risk of VTE, it is currently unclear whether there is a synergetic effect in patients with thrombophilia who undergo orthopedic surgery. METHODS: Data from a large population-based case-control study (the Multiple Environmental and Genetic Assessment [MEGA] of risk factors for venous thrombosis study) were used. Odds ratios (ORs) with 95% confidence intervals (CIs), adjusted for age, sex, and body mass index (BMI) (ORadj) were calculated for patients undergoing any orthopedic intervention. RESULTS: Of 4721 cases and 5638 controls, 263 cases and 94 controls underwent orthopedic surgery. Patients who had any orthopedic intervention in the year before the index date were at higher risk of VTE (ORadj 3.7; 95% CI, 2.9-4.8) than those who did not undergo any orthopedic surgery. There was an additionally increased risk in patients with factor V Leiden (OR 17.5, 95% CI, 4.1-73.6), non-O blood group (OR 11.2; 95% CI, 3.4-34.0), or elevated plasma levels of factor VIII (OR 18.6; 95% CI, 7.4-46.9) all relative to patients without these defects, not undergoing orthopedic surgery. CONCLUSIONS: Patients with factor V Leiden, high levels of factor VIII, or blood group non-O were found to have a high risk of VTE after orthopedic surgery. Identification of these patients may enable individualized thromboprophylactic treatment to efficiently reduce VTE risk.
Assuntos
Procedimentos Ortopédicos , Trombofilia , Tromboembolia Venosa , Trombose Venosa , Estudos de Casos e Controles , Fator V/genética , Humanos , Procedimentos Ortopédicos/efeitos adversos , Fatores de Risco , Trombofilia/complicações , Trombofilia/diagnóstico , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/epidemiologia , Tromboembolia Venosa/etiologiaRESUMO
PURPOSE: Apolipoproteins C-I, C-II, C-III and E have been associated with risk of arterial thrombotic diseases. We investigated whether these apolipoproteins have prothrombotic properties and are associated with risk of venous thromboembolism (VTE). PATIENTS AND METHODS: A total of 127 VTE patients and 299 controls were randomly selected from the Multiple Environmental and Genetic Assessment of Risk Factors for Venous Thrombosis study (1999-2004), in the Netherlands. The apolipoproteins were quantified using mass spectrometry (LC/MS/MS), and their levels were analyzed as continuous variable (per SD increase). RESULTS: In controls, increases in levels of apolipoproteins were associated with increases in levels of vitamin K-dependent factors, factor XI, antithrombin and clot lysis time. Additionally, increasing apolipoproteins C-III and E levels were associated with higher factor VIII and von Willebrand factor levels. Levels of C-reactive protein were not associated with any apolipoprotein. The age- and sex-adjusted odds ratios of apolipoproteins E, C-III, CII and CI to the risk of venous thrombosis were 1.21 (95% CI, 0.98-1.49), 1.19 (95% CI, 0.99-1.44), 1.24 (95% CI, 0.95-1.61) and 1.06 (95% CI, 0.87-1.30) per SD increase, respectively. These odds ratios did not attenuate after adjustments for statin use, estrogen use, BMI, alcohol use, and self-reported diabetes. CONCLUSIONS: Levels of apolipoproteins C-I, C-II, C-III and E are associated with those of several coagulation factors. However, whether these apolipoproteins are also associated with an increased risk of VTE remains to be established.
RESUMO
Venous thromboembolism (VTE) causes a major disease burden worldwide, so that effective preventive measures are warranted. Although oral anticoagulation is effective in preventing VTE episodes, bleeding complications are a major concern that may lead to treatment avoidance. Statin therapy, which is widely used for prevention of arterial cardiovascular disease, is a promising alternative treatment for VTE prophylaxis, as the drug may affect hemostasis without increasing the risk of bleeding. In the past years, clinical studies have suggested that statins can interfere with blood coagulation and, in turn, reduce the risk of VTE. These effects, however, are still regarded with skepticism, as the underlying mechanisms by which statins may affect hemostasis in humans are not clear and data showing that statin therapy reduces VTE risk mostly came from observational studies, while only one randomized trial was conducted to evaluate this issue. In this review, the authors summarize the currently available evidence regarding the effect of statin therapy on coagulation and on VTE prevention. Recent randomized data showed that statin therapy, in particular rosuvastatin, leads to decreased levels of coagulation factors in patients with prior VTE. This evidence provides a reasonable basis for interventional studies necessary to establish the efficacy of statins on reducing the risk of incident and recurrent VTE.
Assuntos
Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Trombofilia/tratamento farmacológico , Tromboembolia Venosa/prevenção & controle , HumanosRESUMO
Essentials The role of statins in hemostasis and venous thromboembolism (VTE) prophylaxis is not clear. This trial assessed whether rosuvastatin use affects thrombin generation in patients with VTE. Endogenous thrombin potential and peak were decreased by 10% and 5% with rosuvastatin therapy. These results provide basis for trials on the efficacy of statins in reducing recurrent VTE risk. SUMMARY: Background Statin therapy could form an alternative prophylactic treatment for venous thromboembolism (VTE) if statins are proven to downregulate hemostasis and prevent recurrent VTE, without increasing bleeding risk. Objectives The STAtins Reduce Thrombophilia (START) trial investigated whether statin affects coagulation in patients with prior VTE. Patients/methods After anticoagulation withdrawal, patients were randomized to rosuvastatin 20 mg day-1 for 4 weeks or no intervention. Plasma samples taken at baseline and at the end of the study were analyzed employing thrombin generation assay. Results and conclusions The study comprised 126 rosuvastatin users and 119 non-users. Mean age was 58 years, 61% were men, 49% had unprovoked VTE and 75% had cardiovascular (CV) risk factors. Endogenous thrombin potential (ETP) increased from baseline to end of study in non-statin users (mean 97.22 nm*min; 95% CI, 40.92-153.53) and decreased in rosuvastatin users (mean -24.94 nm*min; 95% CI, -71.81 to 21.93). The mean difference in ETP change between treatments was -120.24 nm*min (95% CI, -192.97 to -47.51), yielding a 10.4% ETP reduction by rosuvastatin. The thrombin peak increased in both non-statin (mean 20.69 nm; 95% CI, 9.80-31.58) and rosuvastatin users (mean 8.41 nm; 95% CI -0.86 to 17.69). The mean difference in peak change between treatments was -11.88 nm (95% CI, -26.11 to 2.35), yielding a 5% peak reduction by rosuvastatin. Other thrombin generation parameters did not change substantially. The reduction in ETP and peak by rosuvastatin was more pronounced in the subgroups of participants with CV risk factors and with unprovoked VTE. We conclude that rosuvastatin reduces thrombin generation potential in patients who had VTE.