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Background: Post-thrombotic syndrome (PTS) is one of the most frequent complications of venous thromboembolism (VTE) leading to considerable morbidity and cost. Apart from appropriate anticoagulation, there is no drug or medical intervention that helps to prevent PTS. We conducted a multicenter randomized controlled trial to determine whether rosuvastatin can prevent PTS., Methods: 312 patients receiving standard anticoagulation for a newly diagnosed VTE were randomly allocated to adjuvant rosuvastatin 20 mg once daily for 180 days (n = 155) or no rosuvastatin (n = 157). At the last study visit (Day 180 ± 21), an independent observer who was blinded to study treatment performed a PTS assessment using the Villalta scale. The primary clinical outcome of the trial was mean Villalta score at Day 180. We also explored the presence of PTS as defined by Villalta score > 4 at Day 180. Patients mean age was 46.7 ± 10.8 years, 55.8% were female., Results: At Day 180, the Villalta score was 3.5 ± 0.3 in the rosuvastatin arm vs. 3.3 ± 0.3 in the control arm (p = 0.59), and presence of PTS (Villalta >4) was 29.7% in the rosuvastatin arm vs. 25.5% in the control arm (p = 0.41). Secondary analyses showed no difference between trial arms for presence of severe PTS at Day 180 (2.0% vs. 2.7%, p = 1) and for changes in Villalta score between baseline and Day 180 (-3.7 ± 4.4 vs. -4.0 ± 5.0, p = 0.59)., Conclusion: This randomized controlled pilot trial did not demonstrate efficacy of rosuvastatin to reduce Villalta score. Further studies with longer duration of exposure to rosuvastatin are needed., Trial Registration: ClinicalTrials.gov, number NCT02679664., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Introduction: Cell-free DNA (CFDNA) is the major structural component of neutrophil extracellular traps (NETs). CFDNA contributes to the prothrombotic potential of NETs by promoting thrombin generation and inhibiting fibrinolysis. Patients with venous thromboembolism (VTE) have elevated circulating nucleosomes (i.e. DNA-histone complexes). In this study, we investigated if CFDNA contributes to a procoagulant and an antifibrinolytic state in patients with unprovoked VTE., Materials and Methods: Plasma samples from patients with a first episode of unprovoked VTE were obtained from the D-Dimer Optimal Duration Study (DODS). We measured CFDNA plasma levels in 263 patients while on warfarin and 1-month after stopping. Thrombin generation assays and clot lysis assays were measured in patients after stopping warfarin. Comparisons were made with healthy controls., Results: CFDNA levels in VTE patients who stopped warfarin (5.53 μg/mL; 95%CI: 5.34-5.72) were higher than during warfarin therapy (3.11 μg/mL; 95%CI: 2.98-3.25; p < .001), and higher than in healthy controls (2.77 μg/mL; 95%CI: 2.42-3.11; p < .001). VTE patients had a procoagulant state as evidenced by a shorter lag time (30.8 min; 95%CI: 29.2-32.4) compared to controls (48.2 min; 95%CI :41.0-55.5; p < .001) and a greater endogenous thrombin potential (2656 nM∗min; 95%CI: 2479-2836) compared to healthy controls (1198 nM ∗ min; 95%CI: 793-1603). There was a higher proportion of clots generated from patient plasma that were resistant to lysis (43.7%) compared to healthy controls (46.3%; p < .05). CFDNA levels were not associated with enhanced thrombin generation or impaired fibrinolysis in VTE patients., Conclusion: CFDNA levels are elevated in patients with unprovoked VTE but do not correlate with the procoagulant or anti-fibrinolytic properties of patient plasma. This study suggests that additional factors in addition to CFDNA may contribute to the pathogenesis of VTE., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Introduction: A low D-dimer can exclude suspected pulmonary embolism (PE) in cases with low or intermediate clinical probability of disease. Yet D-dimer is nonspecific, so many cases without PE require imaging. D-dimer's specificity is improved by increasing the threshold for a positive test with age (age × 10 ng/mL; age-adjusted D-dimer; AADD) or clinical probability of PE (1000 ng/mL if low and 500 ng/mL if intermediate clinical probability; clinical probability-adjusted D-dimer; CPADD). It is unclear which approach is preferable., Objectives: We report the sensitivity, specificity and negative predictive value (NPV) of AADD compared to CPADD in suspected PE., Materials and Methods: A retrospective cohort of 3500 consecutive cases imaged for suspected PE at two U.S. emergency departments was assembled. We analyzed cases with low or intermediate clinical probability of PE (Revised Geneva Score) who had a D-dimer. The outcome was acute PE on imaging at presentation., Results: Of the 3500 cases, 1745 were eligible. 37% were low, and 63% were intermediate clinical probability of PE. PE was present in 145 (8.3%) cases. Sensitivity of CPADD was 87.5% vs. 96.6% for AADD (difference 9.1%; 95% CI 4.3% to 14.0%). NPV of CPADD was 97.1% vs. 99.0% for AADD (difference 1.9%; 95% CI, 0.7% to 3.1%). Specificity of CPADD was 37.5% vs. 30.2% for AADD (difference -7.3%; 95% CI -9.4% to -5.1%). D-dimer was negative in 35.4% of cases using CPADD vs. 28.0% using AADD., Conclusions: CPADD modestly improved the specificity of D-dimer, but had a lower NPV than AADD. AADD appears preferable in this analysis., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: The assessment of patients with suspected deep vein thrombosis (DVT) remains challenging despite current diagnostic algorithms. (99m)Tc-labelled DI-DD3B6/22-80B3 Fab´ fragments ((99m)Tc-DI-80B3, ThromboView®) is a novel diagnostic test that uses a radiolabelled humanized monoclonal antibody fragment specific for the D-dimer region of cross-linked fibrin to detect DVT. This test has an anatomic component to locate DVT and a functional component to differentiate acute (newly formed) thrombus from inactive (old) thrombus., Methods: In a multi-centre prospective cohort trial we investigated the diagnostic accuracy and safety of (99m)Tc-DI-80B3 in consecutive patients with suspected DVT who had the diagnosis confirmed or excluded by venography., Results: We enrolled 94 patients with suspected DVT of whom 12 did not have (99m)Tc-DI-80B3 imaging, leaving 82 patients for the safety analysis. Of these patients, there were 16 with non-evaluable imaging (11 venography, 7 (99m)Tc-DI-80B3, both in two patients) leaving 66 patients for the accuracy analysis. (99m)Tc-DI-80B3 imaging was well-tolerated: 2 patients developed urticaria; none developed serious adverse events. For proximal DVT, the sensitivity (84.2%; 95% confidence interval [CI]: 62.4-94.5) and specificity (97.6%; CI: 83.3-99.4) were highest when the combined 0.25-hour and 3-hour (99m)Tc-DI-80B3 images were used. The accuracy was lower for distal DVT, irrespective of the images used. There were insufficient patients to comment on the accuracy of (99m)Tc-DI-80B3 imaging for suspected recurrent DVT., Conclusions: (99m)Tc-DI-80B3 (ThromboView®) is a novel diagnostic modality for patients with suspected DVT with a promising accuracy and safety profile that justifies additional clinical development in diagnostic accuracy and clinical management studies., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Objectives: We performed a systematic review to assess the benefits or risks of physical activity in patients with an acute or previous DVT of the leg., Data Sources: PubMed, EMBASE and Science Citation Index were searched without language restrictions up to July 2007. Bibliographies of retrieved articles and personal files were also searched., Review Methods: Randomized trials and prospective cohort studies that included patients with acute or previous DVT, described an exercise intervention or exercise exposure, and described any related clinical outcome were selected. Data were independently extracted by 2 investigators., Results: Seven randomized trials and two prospective observational studies were included. Early exercise, compared with bed rest, was associated with a similar short-term risk of pulmonary embolism in patients with acute DVT and led to more rapid resolution of limb pain. In patients with acute DVT, a 6 month daily walking program led to similar degrees of vein recanalization and improvement in quality of life as controls. In patients with previous DVT, 30 min of vigorous treadmill exercise did not worsen venous symptoms and improved calf muscle flexibility; a 6 month exercise training program improved calf muscle strength and pump function; and high levels of physical activity at one month tended to be associated with reduced severity of postthrombotic symptoms during the subsequent 3 months., Conclusions: Early walking exercise is safe in patients with acute DVT and may help to reduce acute symptoms. Exercise training does not increase leg symptoms acutely in patients with a previous DVT and may help to prevent or improve the postthrombotic syndrome.

Introduction: In patients with new symptoms in a leg previously affected by deep vein thrombosis (DVT), the presence of thrombus on ultrasound cannot be assumed to be due to recurrent thrombosis. Several parameters have been suggested to differentiate between acute and chronic thrombus on ultrasound, including measurement of residual vein diameter during compression, thrombus echogenicity and Doppler assessment of venous flow, but studies on the reproducibility of these measurements are sparse., Objective: To determine interobserver agreement on measurement of residual vein diameter, thrombus echogenicity and Doppler venous flow in patients with residual thrombus in the veins of the lower limb., Materials and Methods: Patients with previous proximal DVT who had a high likelihood of residual thrombosis, but without symptoms of recurrent DVT, had ultrasound examinations independently performed by two examiners on the same day. Interobserver agreement on measurement of residual vein diameter, thrombus echogenicity and Doppler venous flow was evaluated., Results: We determined that interobserver agreement on these measurements was moderate. The mean difference between paired measurements of residual vein diameter was 2.2 mm (95th centile, 8.0 mm). When both examiners agreed residual thrombus was present, 54% of the variance of the measurement of residual vein diameter was accounted for by the paired measurements. The weighted kappa coefficient for thrombus echogenicity was 0.01 and for Doppler venous flow was 0.51., Conclusions: The error associated with ultrasound measurements of residual vein diameter, thrombus echogenicity and flow appears to be considerable.

Background: Patients undergoing rehabilitation after thromboembolic stroke have a relatively high incidence of venous thromboembolism (VTE). Warfarin, with a target international normalized ratio (INR) of 2.0-3.0 is effective for the prevention of VTE. However, because stroke is a major risk factor for bleeding with warfarin, a less intense regimen (target INR < 2.0), might safely prevent VTE in stroke rehabilitation patients., Methods: This study was a randomized, double-blind, placebo-controlled trial of 2 mg of warfarin in patients undergoing rehabilitation following completed stroke. The major efficacy endpoint was symptomatic, objectively proven VTE or asymptomatic VTE detected by monthly duplex ultrasonography (DU) of the proximal leg veins or mandatory bilateral contrast venography performed at the end of the study. The major safety endpoint was bleeding., Results: There were 475 patients screened for enrollment, 355 had one or more exclusion criterion, and 17 had previously undetected proximal DVT on admission. Of the 103 eligible and consenting patients, 56 received warfarin and 47 received placebo. Of the randomized patients, 88 had successful venography (47 warfarin and 41 placebo). In the warfarin group, three (8%) patients had DVT and one (2%) had proximal DVT whereas in the placebo group, seven (20%) had DVT and five (13%) had proximal DVT. The risk ratio for any DVT in warfarin-treated patients relative to placebo-treated patients was 0.39 (95% confidence interval (CI), 0.13-1.37). For proximal DVT, the risk ratio was 0.17 (95% CI, 0.01-1.4). No patients suffered major bleeding., Conclusions: A fixed dose of 2 mg of warfarin per day in patients undergoing stroke rehabilitation is safe and associated with a relative risk reduction of about 80% in the incidence of proximal DVT and 60% in overall DVT., (Copyright 2002 Elsevier Science Ltd.)