Charlotte E.A. Dronkers

Current and future perspectives in imaging of venous thromboembolism

Several thrombus imaging techniques for the diagnosis of venous thromboembolism (VTE) are available. The most prevalent forms of VTE are deep vein thrombosis of the lower extremities and pulmonary embolism. However, VTE may also occur at unusual sites such as deep veins of the upper extremity and the splanchnic and cerebral veins. Currently, the imaging techniques most widely used in clinical practice are compression ultrasonography and computed tomography (CT) pulmonary angiography. Moreover, single‐photon emission CT, CT venography, positron emission tomography, and different magnetic resonance imaging (MRI) techniques, including magnetic resonance direct thrombus imaging, have been evaluated in clinical studies. This review provides an overview of the technique, diagnostic accuracy and potential pitfalls of these established and emerging imaging modalities for the different sites of venous thromboembolism.

Towards a tailored diagnostic standard for future diagnostic studies in pulmonary embolism: communication from the SSC of the ISTH

C. E . A . DRONKERS ,* T . VAN DER HULLE ,* G . LE GAL ,† P . A . KYRLE ,‡§ M. V . HUISMAN,* S . C . CANNEGIETER , ¶ and F . A . KLOK ,* FOR THE SUBCOMMITTEE ON PRED ICT IVE AND DIAGNOST IC VAR IABLES IN THROMBOT IC D ISEASE *Department of Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, the Netherlands; †Department of Medicine and Ottawa Hospital Research Institute, University of Ottawa, Ottawa, ON, Canada; ‡Department of Medicine I, Medical University of Vienna; §Karl Landsteiner Institute of Clinical Thrombosis Research, Vienna, Austria; and ¶Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands

Accurate diagnosis of iliac vein thrombosis in pregnancy with magnetic resonance direct thrombus imaging (MRDTI)

A pregnant woman aged 29 years, G1P0 at 21 weeks of gestation of a dichorionic diamniotic twin, presented with suspected deep vein thrombosis (DVT) of the left leg. Repeated (compression) ultrasonography was not diagnostic for DVT but showed reduced flow over the left external iliac vein, common femoral vein and superficial femoral vein. In pursue of a definite diagnosis, magnetic resonance direct thrombus imaging was performed showing a clear high signal in the left common iliac vein which is diagnostic for acute thrombosis in this venous segment. Phase contrast venography supported this diagnosis, showing no flow in the left common iliac vein. Treatment with anticoagulants was started. 6 months after the diagnosis, the patient is doing well and does not report signs of post-thrombotic syndrome.

Disease prevalence dependent failure rate in diagnostic management studies on suspected deep vein thrombosis: communication from the SSC of the ISTH

C. E . A . DRONKERS ,* Y . M. ENDE -VERHAAR ,* P . A . KYRLE ,† M. R IGHIN I ,‡ S . C . CANNEGIETER ,*§ M. V . HUISMAN,* F . A . KLOK* and FOR THE SUBCOMMITTEE ON PRED ICT IVE AND DIAGNOST IC VAR IABLES IN THROMBOTIC D ISEASE *Department of Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, the Netherlands; †Department of Medicine I, General Hospital Vienna, Vienna, Austria; ‡Division of Angiology and Hemostasis, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland; and §Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands

Caloric restriction lowers endocannabinoid tonus and improves cardiac function in type 2 diabetes

Background/ObjectivesEndocannabinoids (ECs) are associated with obesity and ectopic fat accumulation, both of which play a role in the development of cardiovascular disease (CVD) in type 2 diabetes (T2D). The effect of prolonged caloric restriction on ECs in relation to fat distribution and cardiac function is still unknown. Therefore, our aim was to investigate this relationship in obese T2D patients with coronary artery disease (CAD).Subjects/MethodsIn a prospective intervention study, obese T2D patients with CAD (n = 27) followed a 16 week very low calorie diet (VLCD; 450–1000 kcal/day). Cardiac function and fat accumulation were assessed with MRI and spectroscopy. Plasma levels of lipid species, including ECs, were measured using liquid chromatography-mass spectrometry.ResultsVLCD decreased plasma levels of virtually all measured lipid species of the class of N-acylethanolamines including the EC anandamide (AEA; −15%, p = 0.016), without decreasing monoacylglycerols including the EC 2-arachidonoylglycerol (2-AG). Baseline plasma AEA levels strongly correlated with the volume of subcutaneous white adipose tissue (SAT; R2 = 0.44, p < 0.001). VLCD decreased the volume of SAT (−53%, p < 0.001), visceral white adipose tissue (VAT) (−52%, p < 0.001), epicardial white adipose tissue (−15%, p < 0.001) and paracardial white adipose tissue (−28%, p < 0.001). VLCD also decreased hepatic (−86%, p < 0.001) and myocardial (−33%, p < 0.001) fat content. These effects were accompanied by an increased left ventricular ejection fraction (54.8 ± 8.7–56.2 ± 7.9%, p = 0.016).ConclusionsCaloric restriction in T2D patients with CAD decreases AEA levels, but not 2-AG levels, which is paralleled by decreased lipid accumulation in adipose tissue, liver and heart, and improved cardiovascular function. Interestingly, baseline AEA levels strongly correlated with SAT volume. We anticipate that dietary interventions are worthwhile strategies in advanced T2D, and that reduction in AEA may contribute to the improved cardiometabolic phenotype induced by weight loss.

Evaluation of the new simple and objective clinical decision rule "I-DVT" in patients with clinically suspected acute deep vein thrombosis.

INTRODUCTION The Wells rule is the recommended first step in the work-up of suspected deep vein thrombosis (DVT). However, it is often incorrectly used leading to an excessive number of diagnostic tests used in daily practice and diagnostic failures. A simpler objective risk stratification tool may improve adherence to the guidelines. We evaluated the diagnostic performance of the I-DVT score, which consists of four easy assessable variables: Immobilization, >3cm Difference in calve circumferences, prior Venous thromboembolism (VTE) and active malignant Tumor. METHODS We performed an observational study in 617 consecutive patients with suspected DVT. All patients were managed according to the recommended algorithm starting with the Wells rule followed by D-dimer test and/or compression ultrasonography (CUS). The I-DVT score was prospectively calculated at baseline and evaluated post-hoc. RESULTS The DVT prevalence was 36%. DVT could be excluded in 13% of patients without CUS by the Wells rule and a normal D-dimer test, with a 3-month VTE incidence of 1.2% (95%CI 0.03-6.5%). Using the I-DVT score, DVT would have been excluded in 9.1% of patients without additional CUS, with a 3-month VTE incidence of 0% (95%CI 0.0-6.4%). The area under the ROC curve (AUC) was 0.70 (95%CI 0.66-0.74) and 0.65 (95%CI 0.61-0.70) for the Wells rule and I-DVT score respectively (difference 0.049, 95%CI -0.01-0.11; p=0.13). CONCLUSIONS The simple I-DVT score and Wells rule have comparable diagnostic accuracy. Its safety, efficiency and associated potential improvement of guideline adherence in clinical practice has to be further evaluated in a prospective management study.

Predicting Post-Thrombotic Syndrome with Ultrasonographic Follow-Up after Deep Vein Thrombosis: A Systematic Review and Meta-Analysis

BACKGROUND  Post-thrombotic syndrome (PTS) is a common and potential severe complication of deep venous thrombosis (DVT). Elastic compression stocking therapy may prevent PTS if worn on a daily basis, but stockings are cumbersome to apply and uncomfortable to wear. Hence, identification of predictors of PTS may help physicians to select patients at high risk of PTS. AIMS  This article identifies ultrasonography (US) parameters assessed during or after treatment of DVT of the leg, that predict PTS. METHODS  This is a systematic review and meta-analysis study. Databases were searched for prospective studies including consecutive patients with DVT who received standardized treatment, had an US during follow-up assessing findings consistent with vascular damage after DVT and had a follow-up period of at least 6 months for the occurrence of PTS assessed by a standardized protocol. RESULTS  The literature search revealed 1,156 studies of which 1,068 were irrelevant after title and abstract screening by three independent reviewers. After full-text screening, 12 relevant studies were included, with a total of 2,684 analysed patients. Two US parameters proved to be predictive of PTS: residual vein thrombosis, for a pooled odds ratio (OR) of 2.17 (95% confidence interval [CI], 1.79-2.63) and venous reflux at the popliteal level, for a pooled OR of 1.34 (95% CI, 1.03-1.75). CONCLUSION  The US features reflux and residual thrombosis measured at least 6 weeks after DVT predict PTS. Whether these features may be used to identify patients who may benefit from compression therapy remains to be assessed in further studies.

Diagnosing upper extremity deep vein thrombosis with non-contrast-enhanced Magnetic Resonance Direct Thrombus Imaging: A pilot study

Diagnosing upper extremity deep vein thrombosis (UEDVT) can be challenging. Compression ultrasonography is often inconclusive because of overlying anatomic structures that hamper compressing veins. Contrast venography is invasive and has a risk of contrast allergy. Magnetic Resonance Direct Thrombus Imaging (MRDTI) and Three Dimensional Turbo Spin-echo Spectral Attenuated Inversion Recovery (3D TSE-SPAIR) are both non-contrast-enhanced Magnetic Resonance Imaging (MRI) sequences that can visualize a thrombus directly by the visualization of methemoglobin, which is formed in a fresh blood clot. MRDTI has been proven to be accurate in diagnosing deep venous thrombosis (DVT) of the leg. The primary aim of this pilot study was to test the feasibility of diagnosing UEDVT with these MRI techniques. MRDTI and 3D TSE-SPAIR were performed in 3 pilot patients who were already diagnosed with UEDVT by ultrasonography or contrast venography. In all patients, UEDVT diagnosis could be confirmed by MRDTI and 3D TSE-SPAIR in all vein segments. In conclusion, this study showed that non-contrast MRDTI and 3D TSE-SPAIR sequences may be feasible tests to diagnose UEDVT. However diagnostic accuracy and management studies have to be performed before these techniques can be routinely used in clinical practice.

Persistence to direct oral anticoagulants for acute venous thromboembolism

BACKGROUND Currently, direct oral anticoagulants (DOACs) are the treatment of choice for venous thromboembolism (VTE) in the Netherlands. The main advantages of DOACs over vitamin K antagonists (VKAs) are that they are safer than VKA and that neither monitoring nor dose titrations are needed. A main drawback is a potential risk of lower drug persistence, as compared with VKA treatment, which is strictly controlled by anticoagulation clinics in the Netherlands. OBJECTIVES The primary aim of this study was to audit the persistence to DOAC treatment for acute VTE during the first 2 months in daily clinical practice. METHODS Dispensing data from the Dutch Foundation of Pharmaceutical Statistics were used to monitor persistence to DOAC for treatment of VTE from 1 January 2012-1 April 2016. Non-persistence was defined as the cumulative incidence of patients who completely stopped DOAC or VKA treatment. In addition, we estimated the persistence to VKA treatment for VTE in data from the Anticoagulation Clinic Leiden. RESULTS 1834 patients were selected as DOAC users for the indication VTE. The 2-month cumulative incidence of completely stopping DOAC was 20% (95% confidence interval [CI] 18-24). In the population of 4910 VKA users, 9.1% (95%CI 8.3-9.9) stopped prematurely with VKA. CONCLUSION The stopping rate of 20% we found is in line with other cardiovascular treatments. Further research into the reasons and consequences of prematurely stopping DOAC treatment for acute VTE is urgently needed.

The YEARS algorithm for suspected pulmonary embolism: shorter visit time and reduced costs at the emergency department

Essentials The YEARS algorithm was designed to simplify the diagnostic workup of suspected pulmonary embolism. We compared emergency ward turnaround time of YEARS and the conventional algorithm. YEARS was associated with a significantly shorter emergency department visit time of ˜60 minutes. Treatment of pulmonary embolism was initiated 53 minutes earlier with the YEARS algorithm