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Conventional-intensity warfarin therapy is more effective for preventing recurrent thrombosis in patients who have had unprovoked venous thromboembolism than low-intensity therapy, and conventional-intensity therapy is not associated with an increased [...]

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Venous ultrasonography is the cornerstone of the diagnostic work‐up in patients with suspected deep vein thrombosis (DVT). Significant variations exist in clinical practice between centers and/or countries, e.g. proximal vs. whole‐leg ultrasound, serial tests vs. single test, and combination with clinical probability and D‐dimer testing. Fewer data exist on the need for bilateral leg imaging.

Post‐thrombotic syndrome (PTS) is a frequent chronic complication of deep vein thrombosis (DVT).

There is uncertainty regarding the optimal dosing regimen for the resumption of warfarin after interruption for invasive procedures.

The risk of bleeding on anticoagulation varies between patients. It is uncertain whether sex influences this risk.

Four observations support that anticoagulant therapy for venous thromboembolism (VTE) has an ‘active treatment’ phase that is limited to about 3 months. First, <3 months of treatment is associated with a higher risk of recurrent VTE than treatment for 3 months or longer, suggesting that <3 months is inadequate therapy. Second, treatment for 3 months is associated with the same risk of recurrent VTE as treatment for 6 months or longer, suggesting that 3 months is adequate therapy. Third, the increase in recurrent VTE with too short a course of treatment is predominantly at the site of the initial thrombosis, suggesting reactivation of initial thrombosis. Fourth, the increase in recurrent VTE with too short a course of treatment occurs immediately after treatment is stopped and is short lived, again suggesting reactivation of initial thrombosis. Once the initial thrombosis has been adequately treated (i.e. the first phase of treatment), further anticoagulation serves as ‘secondary prevention’ of new, unrelated, episodes of thrombosis (i.e. the second phase of treatment). For most patients, therefore, anticoagulant therapy for VTE should be stopped at 3 months when the acute episode has completed treatment, or should be continued indefinitely as ‘secondary prevention’ if the risk of recurrence remains unacceptably high having completed ‘active treatment’.

Background: Rate of major bleeding is generally accepted as a good measure of the risks associated with anticoagulant therapy, but this may not be true if the proportion of major bleeds with the most serious consequences differs according to the indication for anticoagulant therapy. Objective:To determine whether the indication for long‐term oral anticoagulant therapy influences the proportion of major bleeds that are intracranial and fatal. Patients/Methods: Two authors abstracted intracranial and fatal bleeds from randomized trials of patients who received anticoagulant therapy for a minimum of 6 months for atrial fibrillation, ischemic heart disease, venous thromboembolism, prosthetic heart valves and ischemic stroke. Results:There were 877 major bleeds among 23 518 patients in 39 studies. The proportion of bleeds that were intracranial was significantly higher in patients with ischemic stroke (36%; 95% CI, 22–52%; P = 0.02) compared with patients with venous thromboembolism (10%; 95% CI, 5–20%). The difference in the proportion of bleeds that were intracranial among atrial fibrillation, ischemic heart disease, venous thromboembolism and prosthetic heart valves was not statistically significant; however, the estimates varied from 10% to 27%. The proportion of bleeds that were fatal did not differ significantly according to indication, but varied from 8% to 20%. For all indications for anticoagulation, intracranial bleeds were much more likely to be fatal than extracranial major bleeds (44% vs. 4% overall). Conclusions: In current practise, the indication for oral anticoagulant therapy has limited influence on the proportion of major bleeds that are intracranial or fatal.

Background: Fatal bleeding is a serious consequence of anticoagulant therapy, but factors associated with fatal bleeding during the first 3 months of treatment of venous thromboembolism (VTE) are uncertain. Methods: Using data from RIETE, an ongoing registry of consecutive patients with acute VTE, we assessed risk factors for fatal bleeding among all patients. We then used this information to derive a clinical model that would stratify a patient’s risk of fatal bleeding during the first 3 months of treatment. Results: Of 24 395 patients, 546 (2.24%) had a major bleed and 135 (0.55%) had a fatal bleed. The gastrointestinal tract was the most common site (40% of fatal bleeds), followed by intracranial bleeding (25%). Fatal bleeding was independently associated with the following factors at the time of VTE diagnosis: age >75 years (OR, 2.16), metastatic cancer (OR, 3.80), immobility ≥ 4 days (OR, 1.99), a major bleed within the past 30 days (OR, 2.64), an abnormal prothrombin time (OR, 2.09), a platelet count < 100 × 109 L−1(OR, 2.23), creatinine clearance < 30 mL min−1(OR, 2.27), anemia (OR, 1.54), and distal deep vein thrombosis (OR, 0.39). INR at the time of bleeding is not known. A clinical prediction rule for risk of fatal bleeding that included nine baseline factors was derived. Fatal bleeding occurred in 0.16% (95% CI, 0.11–0.23) of the low‐risk, 1.06% (95% CI, 0.85–1.30) of the moderate‐risk, and 4.24% (95% CI, 2.76–6.27) of the high‐risk category. Conclusions: Patient characteristics and laboratory variables can identify patients at high risk for fatal bleeding during treatment of VTE.

About half of the patients with a first idiopathic proximal deep vein thrombosis (DVT) or pulmonary embolism (PE) are expected to have a recurrent episode of venous thromboembolism (VTE) within 10 years of stopping therapy, and randomized trials have shown that this group of patients benefit from long-term anticoagulant therapy. High risks for bleeding and patient preference are compelling reasons not to treat such patients long-term. Although a number of factors are associated with a reduced risk of recurrence, they require further validation before it is appropriate to routinely stop anticoagulants after 3 months in patients with idiopathic proximal DVT or PE.

The post-thrombotic syndrome (PTS) is increasingly recognized to be a common and important complication of deep venous thrombosis (DVT). Because there is no ‘gold standard’ objective test to establish its presence, PTS is diagnosed primarily on the basis of the presence of typical symptoms and clinical signs in a limb that was affected by DVT. As a wide variety of definitions of PTS have been used by researchers, it is difficult to compare data across studies and to formally combine data in meta-analyses. In a step towards standardization of the measurement of PTS in clinical studies, available scales and evidence to support their utility to diagnose PTS and to classify its severity were reviewed and discussed at the Control of Anticoagulation Subcommittee of the International Society on Thrombosis and Haemostasis (Vienna, July 2008).

Background:As assessment of clinical pretest probability is the first step in the diagnostic evaluation of deep vein thrombosis (DVT), it is important to know if the clinical features of DVT are the same in men and women.Objectives:To compare the prevalence and clinical characteristics of DVT, and the accuracy of clinical pretest probability assessment, between men and women with suspected DVT.Methods:A retrospective analysis of individual patient data from three prospective studies by our group that evaluated diagnostic tests for a suspected first episode of DVT. Clinical characteristics, clinical pretest probability for DVT, and prevalence and extent of DVT was assessed in a total of 1838 outpatients.Results:The overall prevalence of DVT was higher in men than in women (14.4% vs. 9.4%) (P= 0.001). The prevalence of DVT was higher in men than in women who were categorized as having a clinical pretest probability that was low (6.9% vs. 3.5%;P= 0.025) or moderate (16.9% vs. 8.7%;P= 0.04), but similar in patients in the high category (40.2% vs. 44.0%;P= 0.6). In patients diagnosed with DVT, swelling of the entire leg occurred more often (41.5% vs. 15.7%;P< 0.001), and thrombosis was more extensive (involvement of both popliteal and common femoral veins in 47.9% vs. 21.6%), in women than in men.Conclusions:In outpatients with suspected DVT, the overall prevalence of thrombosis and the prevalence of thrombosis in those with a low or a moderate clinical pretest probability were higher in men than in women.

Background: Individual risk of recurrent venous thromboembolism affects patient management and might differ between men and women. We did a meta-analysis to assess from available evidence whether men and women have the same risk of recurrent venous thromboembolism after stopping anticoagulant treatment. Methods: Eligible articles were identified by searches of MEDLINE (source PubMed, 1966 to February 2005), EMBase (1980 to February 2005), and the Cochrane database 2005, issue 1. Prospective cohort studies and randomised trials were eligible if they included patients with objectively diagnosed venous thromboembolism treated for a minimum of 1 month and followed up for recurrence after anticoagulant treatment was stopped. Data were extracted for study design, study quality, and the number, sex, and age of enrolled patients, risk factors for venous thromboembolism, treatment given, duration of follow-up, and the number of episodes of recurrent venous thrombosis. Findings: 15 studies (nine randomised controlled trials and six prospective observational studies) enrolling a total of 5416 individuals (2729 men), of whom 816 (523 men) had recurrent venous thromboembolism after stopping treatment, were eligible for inclusion. The pooled estimate of the relative risk (RR) of recurrent venous thromboembolism for men compared with for women was 1.6 (95% CI 1.2-2.0). Significant heterogeneity was shown among individual study findings; however, the higher risk of recurrent venous thromboembolism in men than in women was consistent across predefined subgroups. The relative risk for recurrence in men from randomised trials (RR 1.3; 95% CI 1.0-1.8) was lower than that from observational studies (2.1; 1.5-2.9). The lower risk of recurrent venous thromboembolism in women did not seem to be accounted for by a reduced rate of recurrence after venous thromboembolism associated with oestrogen treatment or pregnancy. Interpretation: Men seem to have a 50% higher risk than women of recurrent venous thromboembolism after stopping anticoagulant treatment. If confirmed by further prospective studies, this difference in risk of recurrence should be considered when duration of anticoagulant treatment is determined in individual patients.

Background: Although hormone replacement therapy (HRT) is associated with an increased risk of deep vein thrombosis (DVT), it is not clear if the risk differs in users of combined estrogen‐progestin HRT and estrogen‐only HRT. Methods: We prospectively studied postmenopausal women with suspected DVT in whom HRT use status was ascertained and who subsequently had objective diagnostic testing to confirm or exclude DVT. Cases were patients with idiopathic DVT, in whom there were no DVT risk factors, and controls were patients without DVT, in whom there were also no DVT risk factors. The risk of DVT was determined in users of estrogen‐progestin HRT and estrogen‐only HRT by comparing the prevalence of current HRT use in cases with idiopathic DVT and controls without DVT (reference group). Multivariable regression analysis was done to adjust for factors that might confound an association between HRT use and the risk of DVT. Results: One thousand one hundred and sixty‐eight postmenopausal women with suspected DVT were assessed, from whom 95 cases of idiopathic DVT and 610 controls without DVT and no DVT risk factors were identified. Estrogen‐only HRT was associated with an increased risk for DVT that was not statistically significant [odds ratio (OR) = 1.22; 95% confidence interval (CI) 0.57, 2.61]. Estrogen‐progestin HRT was associated with a greater than 2‐fold increased risk for DVT (OR = 2.70; 95% CI 1.44, 5.07). Conclusion: The risk of developing DVT may be higher in users of combined estrogen‐progestin HRT than in users of estrogen‐only HRT.

Background: Recombinant human soluble thrombomodulin (ART‐123) is composed of the active, extracellular, domain of thrombomodulin. ART‐123 binds to thrombin and this complex converts protein C into the natural anticoagulant activated protein C. This study was performed to identify an effective and safe dose of ART‐123 for prevention of venous thromboembolism after elective, unilateral total hip replacement. Methods and results: An open‐label, sequential, dose‐ranging study was performed in which 312 patients received either 0.3 mg kg−1or 0.45 mg kg−1of ART‐123, subcutaneously, 2–4 h after surgery (day 1). Those who received 0.3 mg kg−1were given a second dose of 0.3 mg kg−1on day 6, and the first 29 of these patients also used intermittent pneumatic compression devices. Those who received 0.45 mg kg−1were not given a second dose. Primary efficacy outcome was all deep vein thrombosis on mandatory bilateral venography performed on day 9 ± 2 and symptomatic venous thromboembolism up to day 11. Primary safety outcome was major bleeding up to day 11. Among patients who did not use intermittent pneumatic compression, venous thromboembolism occurred in 3.4% of 116 evaluable patients in the 0.3 mg kg−1group and 0.9% of 111 patients in the 0.45 mg kg−1group. Major bleeding occurred in 1.4% of 139 patients in the 0.3 mg kg−1group and 6.3% of 144 patients in the 0.45 mg kg−1group. Conclusion: ART‐123 is a highly effective antithrombotic agent that should be directly compared with current methods of prophylaxis in patients who have major orthopedic surgery.

Background: The post‐thrombotic syndrome is a chronic, poorly understood complication of deep venous thrombosis (DVT). Objectives: To evaluate predictors of the post‐thrombotic syndrome, including intensity of long‐term anticoagulation, and to assess the impact of the post‐thrombotic syndrome on quality of life. Patients and methods: The setting was 13 Canadian hospitals and one US hospital. One hundred and forty‐five patients with an unprovoked episode of proximal DVT who were initially treated with 3 months of conventional‐intensity warfarin [target International Normalized Ratio (INR) of 2.5] then participated in a trial comparing two intensities of long‐term warfarin therapy (target INR 2.5 vs. INR 1.7). Post‐thrombotic syndrome was assessed at the end of the trial using a validated clinical scale. Generic and venous disease‐specific quality of life was compared in patients with and without the post‐thrombotic syndrome. Multivariable regression analyses were performed to identify predictors of the post‐thrombotic syndrome and of its severity. Results: After an average follow‐up of 2.2 years, the prevalence of post‐thrombotic syndrome was 37% and of severe post‐thrombotic syndrome was 4%. Quality of life was worse in patients with the post‐thrombotic syndrome compared with patients who did not have it. The presence of factor (F)V Leiden or the prothrombin gene mutation was an independent predictor of both a lower risk (P = 0.006) and reduced severity (P = 0.045) of the post‐thrombotic syndrome. Intensity of anticoagulation did not influence the risk of developing the post‐thrombotic syndrome. Conclusions: The post‐thrombotic syndrome is a frequent and burdensome complication of proximal DVT, even among patients maintained on long‐term oral anticoagulation. While the presence of FV Leiden or prothrombin gene mutation appears to be associated with a reduced risk of post‐thrombotic syndrome, this finding requires further evaluation in prospective studies.

Currently, the same d‐dimer cut‐off point is used to define a positive result for all patients with suspected venous thromboembolism, regardless of their pretest probability. However, use of a relatively high d‐dimer cut‐off point (lower sensitivity) for those with a low clinical pretest probability, and a low d‐dimer cut‐off point (higher sensitivity) for those with a high clinical pretest probability, may be preferable. To determine if using three different d‐dimer cut‐off points according to low, moderate or high clinical pretest probability has greater utility for exclusion of venous thromboembolism than using the same single d‐dimer cut‐off point in all patients. Data from a previously published study of 571 patients was used to identify the highest d‐dimer cut‐off point with a negative predictive value of at least 98% for the subgroup of patients with low and high pretest probability. The d‐dimer cut‐off point for those with moderate clinical pretest probability remained unchanged [0.5 fibrinogen equivalent units (FEU) µg mL−1]. Accuracy of d‐dimer testing for venous thromboembolism using three cut‐off points vs. one cut‐off point was than determined. d‐dimer cut‐off points of 0.2 and 2.1 FEU µg mL−1were selected for the high and low pretest probability groups, respectively. When three pretest probability‐specific cut‐off points were used instead of the previously determined single d‐dimer cut‐off point (0.5 FEU µg mL−1), sensitivity and negative predictive value were unchanged (95 and 98%, respectively), but specificity increased from 44.7 to 60.4% (P < 0.001). This resulted in exclusion of venous thromboembolism in 80 additional patients. Use of three pretest probability‐specific d‐dimer cut‐off points rather than a single d‐dimer cut‐off point for all patients, has the potential to increase the utility of d‐dimer testing for the diagnosis of venous thromboembolism.

Background: The risk of recurrence is lower after treatment of an episode of venous thromboembolism associated with a transient risk factor, such as recent surgery, than after an episode associated with a permanent, or no, risk factor. Retrospective analyses suggest that 1 month of anticoagulation is adequate for patients whose venous thromboembolic event was provoked by a transient risk factor. Methods: In this double‐blind study, patients who had completed 1 month of anticoagulant therapy for a first episode of venous thromboembolism provoked by a transient risk factor were randomly assigned to continue warfarin or to placebo for an additional 2 months. Our goal was to determine if the duration of treatment could be reduced without increasing the rate of recurrent venous thromboembolism during 11 months of follow‐up. Results:  Of 84 patients assigned to placebo, five (6.0%) had recurrent venous thromboembolism, compared with three of 81 (3.7%) assigned to warfarin, resulting in an absolute risk difference of 2.3%[95% confidence interval (CI) − 5.2, 10.0]. The incidence of recurrent venous thromboembolism after discontinuation of warfarin was 6.8% per patient‐year in those who received warfarin for 1 month and 3.2% per patient‐year in those who received warfarin for 3 months (rate difference of 3.6% per patient‐year; 95% CI − 3.8, 11.0). There were no major bleeds in either group. Conclusion: Duration of anticoagulant therapy for venous thromboembolism provoked by a transient risk factor should not be reduced from 3 months to 1 month as this is likely to increase recurrent venous thromboembolism without achieving a clinically important decrease in bleeding.

Introduction:Diagnosing deep vein thrombosis (DVT) is of critical importance because of its associated morbidity and mortality. Diagnosing DVT can be challenging in the Emergency Department (ED) due to inconsistent adherence to, and utilization of the Wells rule. Both the age-adjusted and clinical probability adjusted D-dimer have been shown to decrease ultrasound (US) utilization rates. We aimed to compare the safety and efficacy of the Wells score with D-dimer to the age-adjusted and clinical probability-adjusted D-dimer in Canadian ED patients tested for DVT. Methods:This was a health records review of ED patients investigated for DVT at two EDs over a two-year period. Inclusion criteria were ED physician ordered duplex ultrasonography or D-dimer for investigation of lower limb DVT. Patients under the age of 18 were excluded. DVT was considered to be present during the ED visit if DVT was diagnosed on duplex ultrasonography and was treated for acute DVT, or if the patient was subsequently diagnosed with pulmonary embolism (PE) or DVT during the next 30 days. Trained researchers extracted anonymized data. The Wells D-dimer, age-adjusted D-dimer, and the clinical probability-adjusted D-dimer rules were applied retrospectively. The rate of duplex ultrasonography imaging and the false negative rate was calculated for each rule. Results:Between April 1st 2013 and March 31st 2015, there were 1,198 patients tested for DVT. Of the low and moderate clinical pretest probability patients (Wells score ≤ 2), only 436 had a D-Dimer test and were eligible for our analysis. The average age of the patients was 59, 56% were female, and 4% had a malignancy. 207/436 patients (47.4%, 95%CI 42.8-52.2%) would have had US imaging for DVT if the age-adjusted D-dimer rule was used. 214/436 patients (49.1%, 95%CI 44.4-53.8%) would have had imaging for DVT if the clinical probability-adjusted D-dimer was used. If the Wells rule was used with the standard D-dimer cutoff of 500, 241/436 patients (55.2%, 95%CI 50.6-59.9%) would have had imaging for DVT. The false-negative rate for the Wells rule was 1.5% (95%CI 0.5-4.4%). The false-negative rate for the age-adjusted D-dimer rule was 1.3% (95%CI 0.4-3.8%). The false-negative rate for the clinical-probability adjusted D-Dimer was 1.8% (95%CI 0.7-4.5%). Conclusion:In comparison with the approach of the Wells score and D-dimer, both the age-adjusted and clinical probability-adjusted D-dimer diagnostic strategies could reduce the proportion of patients who require US imaging.

Background:Emergency physicians (EPs) can choose from several evidence-based pathways to diagnose pulmonary embolism (PE), however literature suggests that EPs frequently use computer tomography (CT) scanning as a stand-alone test for PE. This is a program of research to improve adherence to evidence-based PE diagnosis in the emergency department (ED). Aim Statement:To create a novel approach to PE diagnosis in the ED based on a framework explaining EP diagnostic PE behaviour and barriers to using evidence-based PE testing. Measures & Design:We conducted two types of qualitative interviews: 1). EPs in 5 Canadian cities watched videos of 2 simulated cases and then explained how they would test the patient. 2). Semi-structured EP interviews using the theoretical domains framework (TDF). The results of our analyses informed the construction of an explanatory framework for common EP diagnostic PE behaviours. Barriers to evidence-based behaviour were classified into domains. A Canadian EP expert group reviewed these results along with the existing evidence on ED PE diagnostic implementation. We developed a new approach to diagnosis of PE in the ED which addresses each of our domains. Evaluation/Results:We conducted 71 interviews. We identified 4 domains, each addressed in our pathway. ‘PE in a mythical and deadly beast’ PE kills and can masquerade so EPs look for PE in places where it does not exist and are rewarded for ‘over-testing’. Response: Creating a departmental conversation about missing PE, talking about the facts, busting the myths. EP feedback on PE testing including positive rate. ‘The end goal is CTPE’ PE creates anxiety for EPs and ordering a CTPE hands over responsibility to the radiologist. Response: A departmental protocol for PE testing which starts with D-dimer for every patient. Shifting focus to ruling out PE with D-dimer. Protocol is automated once initiated by EP. ‘PERC eases anxiety’ PERC is documented when it is negative and allows EP to stop. Response: EPs can choose to use and document PERC. ‘No-one has been fighting for the Wells score’ Poor understanding of purpose and function. Often at odds to Gestalt. Response: Protocol does not use Wells score. Discussion/Impact:We have developed a new diagnostic PE pathway which addresses current barriers to evidence-based practice which we will evaluate further.

A variety of definitions of major bleeding have been used in published clinical studies, and this diversity adds to the difficulty in comparing data between trials and in performing meta‐analyses. In the first step towards unified definitions of bleeding complications, the definition of major bleeding in non‐surgical patients was discussed at the Control of Anticoagulation Subcommittee of the International Society on Thrombosis and Haemostasis. Arising from that discussion, a definition was developed that should be applicable to studies with all agents that interfere with hemostasis, including anticoagulants, platelet function inhibitors and fibrinolytic drugs. The definition and the text that follows have been reviewed and approved by the cochairs of the subcommittee and the revised version is published here. The intention is to also seek approval of this definition from the regulatory authorities.

Hypercapnic respiratory failure (HRF) is common in advanced COPD. The standard treatment is usually nasal ventilation (NIV) to reduce the blood carbon dioxide level acutely or regular nocturnal use in chronic cases. Not all patients tolerate such treatment and failures occur. Published studies are conflicting showing variable benefit and a 2013 Cochrane review concluded that there was no evidence of significant benefit in any of the measured parameters.1Other studies suggest a reduction in re-admission and death at 1 year between regular nocturnal NIV use and standard care.We have used oral modafinil 200 mg/day as a respiratory stimulant for chronic HRF in COPD without NIV. We present the data from the first 11 cases (6 out of study and 7 in our current open randomised crossover study). The study patients had documented HRF for 6–12 months with PaC02≥6.5 before entry but refused NIV. We present the data at baseline and day 10 and 40 of modafinil, including mean arterial oxygen and carbon dioxide, Daytime and overnight oxygen saturations along with spirometry. We compare these Results with 2 published studies of NIV reported, one after 4 weeks2and the other 12 months.3The study showed a mean improvement by day 40 of +1.8 kPa in Pa02and a reduction in PaCO2by 2.7 kPa. Daytime saturations, improved by +15% and overnight saturations by +11%. FEV-1 and FVC improved by +4%–5% which may reflect reduced acidosis on ventilatory muscles. Compared with studies of nocturnal nasal ventilation, modafinil equalled the effects of NIV and tolerance was excellent. It could provide a cheaper and more effective alternative for patient unable to use long term NIV in HRF.Abstract P219 Table 1Study Data n=11Baseline Pre-modafinilDay 10 modafinil 200 mg/dayDay 40 Modafinil 200 mg/dayImprovement At 40 days4 week NIV2Improvement After 4 weeks Of NIV1 year study of NIV 3Improvement At 1 yearMean Arterial Pa02kPa On air (range)5.8 (4.3–7.3)6.7 (4.1–8.1)7.67 (5.5–9.3)+1.87 kPa7.5 +1.7 7.0+2.4Mean Arterial PaC02kPa On air(range)8.6 (6.5–13.4)6.7 (5.2–8.0)5.9 (5.0–6.3)−2.7 kPa7.5 −0.7 7.2−1.35Mean daytime saturations on air (range)75% (58–89)85% (65–92)90% (79–95)15%No dataNo dataNo dataNo dataMean overnight saturations on air(range)72% (58–86)79% (67–89)83% (68–91)+11%79%0%No dataNo dataMean FEV-1 (%)28%30%32%+4%31%+6%25%−1%Mean FVC (%)48%45%53%+5%No dataNo data54%No dataReferencesN S Hill. JAMA on line21may, 2017.P Sivasothy. ERJ1998;11:34–40.RD McEvoy. Thorax2009;64:561–566.

Introduction:Diagnosing pulmonary embolism (PE) can be challenging because the signs and symptoms are often non-specific. Studies have shown that evidence-based diagnostic algorithms are not always adhered to in the Emergency Department (ED), which leads to unnecessary CT scanning. In 2013, the American College of Chest Physicians identified CT pulmonary angiography as one of the top five avoidable tests. One solution is to use a clinical prediction rule combined with the D-dimer, which safely reduces the use of CT scanning. The objective of this study was to compare the proportion of patients tested for PE in two emergency departments, who 1) had a CT-PE and 2) whose diagnosis of PE was missed. We compared these rates to those if the Wells rule and D-dimer had been applied as standard. Methods:This was a retrospective chart review of ED patients investigated for PE at two hospitals from April 2013 to March 2015 (24 months). Inclusion criteria were the ED physician ordered CT-PE, Ventilation-Perfusion (VQ) scan or D-dimer for investigation of PE. Patients under the age of 18 were excluded. PE was defined as CT/VQ diagnosis of acute PE or acute PE/DVT in 30-day follow-up. Trained researchers extracted anonymized data. The rate of CT/VQ imaging and the false-negative rates were calculated. The false-negative rate was calculated as the number of patients diagnosed with PE within 30 days as a proportion of those patients who did not have a CT/VQ scan at initial presentation. Results:There were 1,189 patients included in this study. 55/1,189 patients (4.6%; 95%CI 3.6-6.0%) were ultimately diagnosed with PE within 30 days. 397/1,189 patients (33.4%; 95%CI 30.8-36.1%) had CT/VQ scans for PE. 3 out of 792 who were not scanned had a missed PE resulting in a false-negative rate of 0.4% (95% CI 0.1-1.1%). 80 patients had an elevated D-dimer or high Wells score but were not imaged. Furthermore, 75 patients who did not have an elevated D-dimer nor a high Wells score were imaged. Had Wells rule/D-dimer been adhered to, 402/1,189 patients (33.8%; 95%CI 31.9-36.6%) would have undergone imaging and the false negative rate would be 0/727, 0% (95%CI 0.0-0.5%). Conclusion:If the Wells rule and D-dimer was used in all patients tested for PE, a similar proportion would have a CT scan but fewer PEs would be missed.

Introduction:Diagnosing pulmonary embolism (PE) in the emergency department can be challenging due to non-specific signs and symptoms; this often results in the over-utilization of CT pulmonary angiography (CT-PA). In 2013, the American College of Chest Physicians identified CT-PA as one of the top five avoidable tests. Age-adjusted D-dimer has been shown to decrease CT utilization rates. Recently, clinical-probability adjusted D-dimer has been promoted as an alternative strategy to reduce CT scanning. The aim of this study is to compare the safety and efficacy of the age-adjusted D-dimer rule and the clinical probability-adjusted D-dimer rule in Canadian ED patients tested for PE. Methods:This was a retrospective chart review of ED patients investigated for PE at two hospitals from April 2013 to March 2015 (24 months). Inclusion criteria were the ED physician ordered CT-PA, Ventilation-Perfusion (VQ) scan or D-dimer for investigation of PE. Patients under the age of 18 were excluded. PE was defined as CT/VQ diagnosis of acute PE or acute PE/DVT in 30-day follow-up. Trained researchers extracted anonymized data. The age-adjusted D-dimer and the clinical probability-adjusted D-dimer rules were applied retrospectively. The rate of CT/VQ imaging and the false negative rates were calculated. Results:In total, 1,189 patients were tested for PE. 1,129 patients had a D-dimer test and a Wells score less than 4.0. 364/1,129 (32.3%, 95%CI 29.6-35.0%) would have undergone imaging for PE if the age-adjusted D-dimer rule was used. 1,120 patients had a D-dimer test and a Wells score less than 6.0. 217/1,120 patients (19.4%, 95%CI 17.2-21.2%) would have undergone imaging for PE if the clinical probability-adjusted D-dimer rule was used. The false-negative rate for the age-adjusted D-dimer rule was 0.3% (95%CI 0.1-0.9%). The false-negative rate of the clinical probability-adjusted D-dimer was 1.0% (95%CI 0.5-1.9%). Conclusion:The false-negative rates for both the age-adjusted D-dimer and clinical probability-adjusted D-dimer are low. The clinical probability-adjusted D-dimer results in a 13% absolute reduction in CT scanning compared to age-adjusted D-dimer.

ObjectiveTo assess the accuracy of the Wells rule for excluding deep vein thrombosis and whether this accuracy applies to different subgroups of patients.DesignMeta-analysis of individual patient data. Data sourcesAuthors of 13 studies (n=10 002) provided their datasets, and these individual patient data were merged into one dataset.Eligibility criteriaStudies were eligible if they enrolled consecutive outpatients with suspected deep vein thrombosis, scored all variables of the Wells rule, and performed an appropriate reference standard.Main outcome measuresMultilevel logistic regression models, including an interaction term for each subgroup, were used to estimate differences in predicted probabilities of deep vein thrombosis by the Wells rule. In addition, D-dimer testing was added to assess differences in the ability to exclude deep vein thrombosis using an unlikely score on the Wells rule combined with a negative D-dimer test result.ResultsOverall, increasing scores on the Wells rule were associated with an increasing probability of having deep vein thrombosis. Estimated probabilities were almost twofold higher in patients with cancer, in patients with suspected recurrent events, and (to a lesser extent) in males. An unlikely score on the Wells rule (≤1) combined with a negative D-dimer test result was associated with an extremely low probability of deep vein thrombosis (1.2%, 95% confidence interval 0.7% to 1.8%). This combination occurred in 29% (95% confidence interval 20% to 40%) of patients. These findings were consistent in subgroups defined by type of D-dimer assay (quantitative or qualitative), sex, and care setting (primary or hospital care). For patients with cancer, the combination of an unlikely score on the Wells rule and a negative D-dimer test result occurred in only 9% of patients and was associated with a 2.2% probability of deep vein thrombosis being present. In patients with suspected recurrent events, only the modified Wells rule (adding one point for the previous event) is safe.ConclusionCombined with a negative D-dimer test result (both quantitative and qualitative), deep vein thrombosis can be excluded in patients with an unlikely score on the Wells rule. This finding is true for both sexes, as well as for patients presenting in primary and hospital care. In patients with cancer, the combination is neither safe nor efficient. For patients with suspected recurrent disease, one extra point should be added to the rule to enable a safe exclusion.