Safety of D-dimer testing as a stand-alone test for the exclusion of deep vein thrombosis as compared with other strategies.

Essentials The aim of deep vein thrombosis (DVT) diagnostic work-up is to maximize both safety and efficiency. We explored whether D-dimer is safe and efficient as a stand-alone test to exclude DVT. Our findings suggest it is a safe, efficient and simplified diagnostic strategy. The safety of age-adjusted D-dimer as a stand-alone test requires further investigation. SUMMARY: Background Several strategies for safely excluding deep vein thrombosis (DVT) while limiting the number of imaging tests have been explored. Objectives To determine whether D-dimer testing could safely and efficiently exclude DVT as a stand-alone test, and evaluate its performance as compared with strategies that incorporate the Wells score and age-adjusted D-dimer. Patients/Methods We included consecutive outpatients referred with suspected DVT to the Emergency Department at Østfold Hospital, Norway. STA-Liatest D-Di PLUS D-dimer was analyzed for all patients. Patients with a D-dimer level of ≥ 0.5 µg mL-1 were referred for compression ultrasonography (CUS). In patients with a D-dimer level of < 0.5 µg mL-1 , no further testing was performed and anticoagulation was withheld. Patients were followed for 3 months for venous thromboembolism (VTE). Results Of the 913 included patients, 298 (33%) had a negative D-dimer result. One hundred and seventy-three patients (18.9%) were diagnosed with DVT at baseline. One of 298 patients had DVT despite having a negative D-dimer result, resulting in a failure rate of 0.3% (95% confidence interval [CI] 0.1-1.9%). Adding the modified Wells score would have yielded a failure rate of 0.0% (95% CI 0.0-1.8%) while necessitating 87 more CUS examinations. Age-adjusted D-dimer as a stand-alone test would have necessitated 80 fewer CUS examinations than fixed D-dimer as a stand-alone test, at the cost of a failure rate of 1.6% (95% CI 0.7-3.4%). Conclusions This outcome study shows that a negative high-sensitivity D-dimer result safely excludes DVT in an outpatient population, and necessitates fewer CUS than if used in combination with Wells score. The safety of stand-alone age-adjusted D-dimer needs further assessment in prospective outcome studies.

Rivaroxaban versus warfarin for the prevention of post-thrombotic syndrome.

INTRODUCTION: Despite treatment of acute deep vein thrombosis (DVT) with low molecular weight heparin and warfarin, up to 50% of patients develop post-thrombotic syndrome (PTS). Our aims were to assess whether treatment of DVT with rivaroxaban would reduce the rate of subsequent PTS and improve health-related quality of life (HRQoL) as compared to conventional anticoagulation with low molecular weight heparin (LMWH)/warfarin. MATERIALS AND METHODS: Consecutive patients with an objectively confirmed DVT diagnosed between 2011 and 2014 and treated with either rivaroxaban or warfarin were included in this study 24 (±6) months after DVT. PTS was assessed using the Patient Reported Villalta scale. HRQoL was assessed using the EQ-5D-3L and VEINES-QOL/Sym questionnaires. RESULTS: Total 309 patients were included, 161 (52%) treated with rivaroxaban and 148 (48%) with warfarin. Rivaroxaban-treated patients had a lower rate of PTS (45%: 95% confidence interval [CI] 37 to 52) compared to those treated with warfarin (59%: 95% CI 51 to 66, absolute risk difference 14%: 95% CI 3 to 25, odds ratio (OR) 0.6, P = .01). The adjusted OR for development of PTS was 0.5 (95% CI: 0.3 to 0.8, P = .01) in patients treated with rivaroxaban. HRQoL was significantly better in the rivaroxaban-treated patients. HRQoL measured by EQ-VAS (P = .002) and VEINES-QOL/Sym (P = .005/P = .003) remained significantly better after adjustment. CONCLUSIONS: Patients treated with rivaroxaban had lower rate of PTS and better HRQoL after DVT compared to patients treated with warfarin. However, these results should be interpreted with caution due to the limitation imposed by study design.

Cost-effectiveness of additional catheter-directed thrombolysis for deep vein thrombosis.

BACKGROUND: Additional treatment with catheter-directed thrombolysis (CDT) has recently been shown to reduce post-thrombotic syndrome (PTS). OBJECTIVES: To estimate the cost effectiveness of additional CDT compared with standard treatment alone. METHODS: Using a Markov decision model, we compared the two treatment strategies in patients with a high proximal deep vein thrombosis (DVT) and a low risk of bleeding. The model captured the development of PTS, recurrent venous thromboembolism and treatment-related adverse events within a lifetime horizon and the perspective of a third-party payer. Uncertainty was assessed with one-way and probabilistic sensitivity analyzes. Model inputs from the CaVenT study included PTS development, major bleeding from CDT and utilities for post DVT states including PTS. The remaining clinical inputs were obtained from the literature. Costs obtained from the CaVenT study, hospital accounts and the literature are expressed in US dollars ($); effects in quality adjusted life years (QALY). RESULTS: In base case analyzes, additional CDT accumulated 32.31 QALYs compared with 31.68 QALYs after standard treatment alone. Direct medical costs were $64,709 for additional CDT and $51,866 for standard treatment. The incremental cost-effectiveness ratio (ICER) was $20,429/QALY gained. One-way sensitivity analysis showed model sensitivity to the clinical efficacy of both strategies, but the ICER remained < $55,000/QALY over the full range of all parameters. The probability that CDT is cost effective was 82% at a willingness to pay threshold of $50,000/QALY gained. CONCLUSIONS: Additional CDT is likely to be a cost-effective alternative to the standard treatment for patients with a high proximal DVT and a low risk of bleeding.

Prevalence and predictors for post-thrombotic syndrome 3 to 16 years after pregnancy-related venous thrombosis: a population-based, cross-sectional, case-control study.

BACKGROUND: The long-term outcome of pregnancy-related venous thrombosis (VT) is not known. OBJECTIVES: To assess predictors and long-term frequency of post-thrombotic syndrome (PTS) after pregnancy-related VT. PATIENTS/METHODS: In 2006, 313 women with pregnancy-related VT during 1990-2003 and 353 controls answered a comprehensive questionnaire that included self-reported Villalta score as a measure of PTS. Cases were identified from 18 Norwegian hospitals using the Norwegian Patient Registry and the Medical Birth Registry of Norway. The latter was used to select as possible controls women who gave birth at the same time as a case. Thirty-nine patients and four controls were excluded because of VT outside the lower limbs/lungs or missing Villalta scores. Two hundred and four patients had DVT in the lower limb and 70 had pulmonary embolism (PE). The control group comprised 349 women naive for VT at the time of the index pregnancy. RESULTS: Forty-two per cent of cases with DVT in the lower limb, compared with 24% of cases with PE and 10% of controls, reported a Villalta score of ≥ 5. Severe PTS (Villalta score of ≥ 15) was reported among 7%, 4% and 1%. Proximal postnatal, but not antenatal, thrombosis was a strong predictor of PTS with an adjusted odds ratio of 6.3 (95% confidence interval, 2.0-19.8; P = 0.002). Daily smoking before the index pregnancy and age above 33 years at event were independent predictors for post-thrombotic syndrome. CONCLUSIONS: PTS is a common long-term complication after pregnancy-related DVT. Proximal postnatal thrombosis, smoking and higher age were independent predictors of the development of PTS.

Long-term quality of life after pregnancy-related deep vein thrombosis and the influence of socioeconomic factors and comorbidity.

BACKGROUND: Little is known about the long-term impact of pregnancy-related deep vein thrombosis (DVT) of the lower limbs. OBJECTIVES: To evaluate the long-term consequences of pregnancy-related DVT by assessment of self-reported, disease-specific quality of life (QOL) and symptom severity using the Venous Insufficiency Epidemiological and Economic Study (VEINES)-QOL/Sym questionnaire, and to investigate the influence of socioeconomic factors and comorbidity. PATIENTS/METHODS: In this cross-sectional case-control study, 313 women with validated pregnancy-related DVT and 353 controls completed a comprehensive questionnaire, including the disease-specific VEINES-QOL/Sym questionnaire. After exclusion of DVT outside the lower limbs and missing scores, the study population comprised 208 patients and 347 controls. A VEINES-QOL/Sym score < the 25th percentile was defined as a clinically relevant reduced outcome compared with scores ≥ the 50th percentile. Predictors for low scores were identified in multivariate logistic regression models. RESULTS: Cases reported lower mean VEINES-QOL/Sym scores than controls, 45.6/45.4 vs. 52.8/52.7, respectively (P < 0.001), and QOL among cases was still reduced compared with controls when adjusted for possible confounders. Low education was an independent predictor for both low VEINES-QOL and VEINES-Sym scores, and in addition being married/cohabitating predicted low VEINES-Sym scores. CONCLUSIONS: Long-term QOL and symptom scores as assessed with the VEINES-QOL/Sym questionnaire were lower in women with previous pregnancy-related DVT than in controls, and also when adjusted for possible confounders. By logistic regression, low education was an independent predictor for low scores. This supports the use of the VEINES-QOL/Sym questionnaire in studies on pregnancy-related DVT.