Best Evidence Topic report: Antithrombotic therapy and endovascular intervention for blunt cerebrovascular injury.

A short cut review of the literature was carried out to examine the evidence supporting antithrombotic treatment and/or endovascular therapy to reduce mortality and/or prevent future stroke following blunt cerebrovascular injury (BCVI). Five papers were identified as suitable for inclusion using the reported search strategy. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of the best papers are tabulated. It is concluded that in patients with BCVI confirmed by CT angiography, there is limited evidence to support screening for, or treating BCVI. In confirmed BCVI where the risk of stroke is felt to outweigh the risk of bleeding, antiplatelet therapy appears to be as effective as therapeutic anticoagulation.

Venous thromboembolism risk following temporary immobilisation after injury: evaluation of the Aberdeen VTE risk tool.

BACKGROUND: Temporary lower limb immobilisation following injury is a risk factor for symptomatic venous thromboembolism (VTE). Pharmacological thromboprophylaxis can mitigate this risk but it is unclear which patients benefit from this intervention. The Aberdeen VTE risk tool was developed to tailor thromboprophylaxis decisions in these patients and this evaluation aimed to describe its performance in clinical practice. Secondarily, diagnostic metrics were compared with other risk assessment methods (RAMs). METHODS: A prospective cohort service evaluation was conducted. Adult patients (≥16 years) managed with lower limb immobilisation for injury who were evaluated with the Aberdeen VTE risk tool prior to discharge from the ED were identified contemporaneously between February 2014 and December 2020. Electronic patient records were scrutinised up to 3 months after removal of immobilisation for the development of symptomatic VTE or sudden death due to pulmonary embolism (PE). Other RAMs, including the Thrombosis Risk Prediction for Patients with cast immobilisation (TRiP(cast)) and Plymouth scores, were assimilated retrospectively and diagnostic performance compared. RESULTS: Of 1763 patients (mean age 46 (SD 18) years, 51% women), 15 (0.85%, 95% CI 0.52% to 1.40%) suffered a symptomatic VTE or death due to PE. The Aberdeen VTE tool identified 1053 (59.7%) patients for thromboprophylaxis with a sensitivity of 80.0% (95% CI 54.8% to 93.0%) and specificity of 40.4% (95% CI 38.1% to 42.6%) for the primary outcome. In 1695 patients, fewer were identified as high risk by the TRiP(cast) (33.3%) and Plymouth (24.4%) scores, but with greater specificity, 67.0% and 75.6%, respectively, than dichotomous RAMs, including the Aberdeen VTE tool. CONCLUSION: Routine use of the Aberdeen VTE tool in our population resulted in an incidence of symptomatic VTE of less than 1%. Ordinal RAMs, such as the TRiP(cast) score, may more accurately reflect VTE risk and permit more individually tailored thromboprophylaxis decisions but prospective comparison is needed.

Pulmonary embolism management in the emergency department: part 2.

Pulmonary embolism (PE) can present with a range of severity. Prognostic risk stratification is important for efficacious and safe management. This second of two review articles discusses the management of high-, intermediate- and low-risk PE. We discuss strategies to identify patients suitable for urgent outpatient care in addition to identification of patients who would benefit from thrombolysis. We discuss specific subgroups of patients where optimal treatment differs from the usual approach and identify emerging management paradigms exploring new therapies and subgroups.

Could a D-dimer/fibrinogen ratio have a role in ruling-out venous thromboembolism?

BACKGROUND: Diagnosis of venous thromboembolism (VTE) requires chest CT angiography for pulmonary embolism and venous ultrasound for deep vein thrombosis. To reduce imaging, guidelines recommend D-dimer levels to rule-out VTE in patients with a low pre-test probability. The most widely used D-dimer cut-off is 500 ng/mL. This cut-off has low specificity, meaning many patients without disease require imaging. METHODS: In this retrospective chart review, we evaluated the diagnostic performance of the D-dimer/fibrinogen ratio (DFR) for identifying thromboembolism and compared it to the performance of two different D-dimer cut-offs (500 ng/mL and 1000 ng/mL) in patients who underwent a chest CT angiography or a venous ultrasound in the ED of San Raffaele Hospital, Italy, in 2017. Patients had a retrospective Wells score calculated after chart review, identifying both high-risk and low-risk pre-test probability patients for this study and low probability patients were further stratified into low-risk of deep vein thrombosis or pulmonary embolism. RESULTS: Enrolled patients included 92 with suspected pulmonary embolism and 154 with suspected deep vein thrombosis; of whom 67 (27%) were diagnosed with VTE. The most accurate cut-off for DFR in terms of discriminative power was 2.65. In the whole sample and in low-risk patients, this cut-off had the same sensitivity values of the 500 ng/mL D-dimer cut-off (97% (95% CI: 89.8% to 99.2%)), while slightly lower sensitivity values were found for the 1000 ng/mL D-dimer cut-off (95.5% (95% CI: 87.6% to 98.5%)). Specificity was higher for the 2.65 DFR cut-off (55.3% (95% CI: 48.0% to 62.4%)) in the whole sample compared with both 500 ng/mL D-dimer cut-off (22.9% (95% CI: 17.4% to 29.6%)) and 1000 ng/mL D-dimer cut-off (45.8% (95% CI: 38.7% to 53.1%)). Similar results were found in all subgroups. CONCLUSION: A DFR, with a cut-off of 2.65, may improve the specificity for VTE patients when compared with D-dimer alone in high-risk VTE emergency medicine populations. This is exploratory information only, needing evaluation in prospective, multicentre studies, prior to consideration for use in routine clinical work.

Pulmonary embolism diagnosis part 1: clinical assessment at the front door.

This first of two practice reviews addresses pulmonary embolism (PE) diagnosis considering important aspects of PE clinical presentation and comparing evidence-based PE testing strategies. A companion paper addresses the management of PE. Symptoms and signs of PE are varied, and emergency physicians frequently use testing to 'rule out' the diagnosis in people with respiratory or cardiovascular symptoms. The emergency clinician must balance the benefit of reassuring negative PE testing with the risks of iatrogenic harms from over investigation and overdiagnosis.

Accuracy of PE rule-out strategies in pregnancy: secondary analysis of the DiPEP study prospective cohort.

OBJECTIVE: Recent studies suggest that combinations of clinical probability assessment (the YEARS algorithm or Geneva score) and D-dimer can safely rule out suspected pulmonary embolism (PE) in pregnant women. We performed a secondary analysis of the DiPEP (Diagnosis of Pulmonary Embolism in Pregnancy) study data to determine the diagnostic accuracy of these strategies. METHODS: The DiPEP study prospectively recruited and collected data and blood samples from pregnant/postpartum women with suspected PE across 11 hospitals and retrospectively collected data from pregnant/postpartum women with diagnosed PE across all UK hospitals (15 February 2015 to 31 August 2016). We selected prospectively recruited pregnant women who had definitive diagnostic imaging for this analysis. We used clinical data and D-dimer results to determine whether the rule out strategies would recommend further investigation. Two independent adjudicators used data from imaging reports, treatments and adverse events up to 30 days to determine the reference standard. RESULTS: PEs were diagnosed in 12/219 (5.5%) women. The YEARS/D-dimer strategy would have ruled out PE in 96/219 (43.8%) but this would have included 5 of the 12 with PEs. Sensitivity for PE was 58.3% (95% CI 28.6% to 83.5%) and specificity 44.0% (37.1% to 51.0%). The Geneva/D-dimer strategy would have ruled out PE in 46/219 (21.0%) but this would have included three of the 12 with PE. Sensitivity was 75.0% (95% CI 42.8% to 93.3%) and specificity 20.8% (95% CI 15.6% to 27.1%). Administration of anticoagulants prior to blood sampling may have reduced D-dimer sensitivity for small PE. CONCLUSION: Strategies using clinical probability and D-dimer have limited diagnostic accuracy and do not accurately rule out all PE in pregnancy. It is uncertain whether PE missed by these strategies lead to clinically important consequences.

Thromboprophylaxis in lower limb immobilisation after injury (TiLLI).

Venous thromboembolic disease is a major global cause of morbidity and mortality. An estimated 10 million episodes are diagnosed yearly; over half of these episodes are provoked by hospital admission/procedures and result in significant loss of disability adjusted life years. Temporary lower limb immobilisation after injury is a significant contributor to the overall burden of venous thromboembolism (VTE). Existing evidence suggests that pharmacological prophylaxis could reduce overall VTE event rates in these patients, but the proportional reduction of symptomatic events remains unclear. Recent studies have used different pharmacological agents, dosing regimens and outcome measures. Consequently, there is wide variation in thromboprophylaxis strategies, and international guidelines continue to offer conflicting advice for clinicians. In this review, we provide a summary of recent evidence assessing both the clinical and cost effectiveness of thromboprophylaxis in patients with temporary immobilisation after injury. We also examine the evidence supporting stratified thromboprophylaxis and the validity of widely used risk assessment methods.

Development and implementation of a COVID-19 near real-time traffic light system in an acute hospital setting.

Common causes of death in COVID-19 due to SARS-CoV-2 include thromboembolic disease, cytokine storm and adult respiratory distress syndrome (ARDS). Our aim was to develop a system for early detection of disease pattern in the emergency department (ED) that would enhance opportunities for personalised accelerated care to prevent disease progression. A single Trust's COVID-19 response control command was established, and a reporting team with bioinformaticians was deployed to develop a real-time traffic light system to support clinical and operational teams. An attempt was made to identify predictive elements for thromboembolism, cytokine storm and ARDS based on physiological measurements and blood tests, and to communicate to clinicians managing the patient, initially via single consultants. The input variables were age, sex, and first recorded blood pressure, respiratory rate, temperature, heart rate, indices of oxygenation and C-reactive protein. Early admissions were used to refine the predictors used in the traffic lights. Of 923 consecutive patients who tested COVID-19 positive, 592 (64%) flagged at risk for thromboembolism, 241/923 (26%) for cytokine storm and 361/923 (39%) for ARDS. Thromboembolism and cytokine storm flags were met in the ED for 342 (37.1%) patients. Of the 318 (34.5%) patients receiving thromboembolism flags, 49 (5.3% of all patients) were for suspected thromboembolism, 103 (11.1%) were high-risk and 166 (18.0%) were medium-risk. Of the 89 (9.6%) who received a cytokine storm flag from the ED, 18 (2.0% of all patients) were for suspected cytokine storm, 13 (1.4%) were high-risk and 58 (6.3%) were medium-risk. Males were more likely to receive a specific traffic light flag. In conclusion, ED predictors were used to identify high proportions of COVID-19 admissions at risk of clinical deterioration due to severity of disease, enabling accelerated care targeted to those more likely to benefit. Larger prospective studies are encouraged.

Role of physician perception of patient smile on pretest probability assessment for acute pulmonary embolism.

BACKGROUND: Many clinicians use a global visual interpretation of patient appearance to decide if a patient looks sick or not. For patients with suspected acute pulmonary embolism (PE), we tested the relationship between visual appearance of a happy patient facial affect and probability of PE+ on CT pulmonary angiography (CTPA). METHODS: Eligible patients were selected by usual care to undergo CTPA, the criterion standard for PE+ or PE-. Prior to CTPA result, trained study personnel obtained physician pretest probability using the gestalt method (visual analogue scale, 0%-100%), the Wells score (0-12) and physicians' impression of whether the patient smiled during the initial examination (smile+). Patients' faces were also video recorded and analysed with an automated neural network-based algorithm (Noldus FaceReader) for happy affect. RESULTS: Of the 208 patients enrolled, 27 were PE+ and smile+ was more frequent in patients with PE+ than PE-, a finding confirmed by the Noldus. The diagnostic sensitivity and specificity of smile was low, and physicians overestimated presence of an alternative diagnosis more likely to PE with smile+ than smile- patients in patients with true PE. As a result, the area under the receiver operating characteristic curve (AUROC) was lower for the Wells score in smile+ patients. However, the physicians' mean gestalt estimate of PE did not differ with smile status, nor did smile status affect the AUROC for gestalt. CONCLUSIONS: In patients with suspected PE, physician recollection of patients' smile+ was more common in PE+ patients, and was associated with a less accurate Wells score, primarily because physicians overestimated probability of alternative diagnosis. However, the overall diagnostic accuracy of physicians' gestalt did not differ with perceived smile status. These data suggest that the patients' smile had less effect on the numeric gestalt pretest probability assessment than on the binary decision about an alternative diagnosis.

Should we be looking for and treating isolated calf vein thrombosis?

Management of isolated calf deep vein thrombosis is an area of significant international debate and variable clinical practice. Both therapeutic anticoagulation and conservative management carry risk. As clinical care of suspected and confirmed venous thromboembolic disease increasingly becomes the remit of emergency medicine, complex decisions are left to practising clinicians at the front door. We aim to provide a contemporary overview of recent evidence on this topic and associated challenges facing clinicians. Given the lack of high-level evidence, we present this work as a narrative review, based on structured literature review and expert opinion. A decision to manage calf thrombosis is principally dependent on the risk of complications without treatment balanced against the risks of therapeutic anticoagulation. Estimates of the former risks taken from systematic review, meta-analysis, observational cohort and recent pilot trial evidence include proximal propagation 7%-10%, pulmonary embolism 2%-3% and death <1%. Fatal bleeding with therapeutic anticoagulation stands at <0.5%, and major bleeding at approximately 2%. Estimates of haemorrhagic risk are based on robust data from large prospective management studies of venous thromboembolic disease; the risks of untreated calf deep vein thrombosis are based on small cohorts and therefore less exact. Pending further trial evidence, these risks should be discussed with patients openly, in the context of personal preference and shared decision-making. Anticoagulation may maximally benefit those patients with extensive and/or symptomatic disease or those with higher risk for complication (unprovoked, cancer-associated or pregnancy).

A retrospective analysis of the combined use of PERC rule and Wells score to exclude pulmonary embolism in the Emergency Department.

BACKGROUND: The pulmonary embolism rule-out criteria (PERC) rule is an eight-factor decision rule to support the decision not to order a diagnostic test when the gestalt-based clinical suspicion on pulmonary embolism (PE) is low. METHODS: In a retrospective cohort study, we determined the accuracy of a negative PERC (0) in patients with a low Wells score (<2) to rule-out PE, and compared this to the accuracy of the default algorithm used in our hospital (a low Wells score in combination with a negative D-dimer). RESULTS: During the study period, 377 patients with a Wells score <2 were included. CT pulmonary angiography (CTPA) was performed in 86 patients, and V/Q scintigraphy in one patient. PE was diagnosed in 18 patients. 78 patients (21%) had a negative PERC score. When further diagnostic studies would have been omitted in these patients, two (subsegmental) PEs would have been missed, resulting in a sensitivity of 89% (64%-98%) and a negative likelihood ratio (LR-) of 0.52 (0.14-1.97). The default algorithm missed one (subsegmental) PE, resulting in a sensitivity of 95% (71%-99%) and an LR- of 0.25 (0.04-1.73). CONCLUSIONS: The combination of a Wells score <2 and a PERC rule of 0 had a suboptimal sensitivity for excluding PE in our sample of patients presenting in the ED. Further studies are warranted to test this algorithm in larger populations.

Thrombosis in vasculitis: from pathogenesis to treatment.

In recent years, the relationship between inflammation and thrombosis has been deeply investigated and it is now clear that immune and coagulation systems are functionally interconnected. Inflammation-induced thrombosis is by now considered a feature not only of autoimmune rheumatic diseases, but also of systemic vasculitides such as Behçet's syndrome, ANCA-associated vasculitis or giant cells arteritis, especially during active disease. These findings have important consequences in terms of management and treatment. Indeed, Behçet'syndrome requires immunosuppressive agents for vascular involvement rather than anticoagulation or antiplatelet therapy, and it is conceivable that also in ANCA-associated vasculitis or large vessel-vasculitis an aggressive anti-inflammatory treatment during active disease could reduce the risk of thrombotic events in early stages. In this review we discuss thrombosis in vasculitides, especially in Behçet's syndrome, ANCA-associated vasculitis and large-vessel vasculitis, and provide pathogenetic and clinical clues for the different specialists involved in the care of these patients.

When should we use diagnostic imaging to investigate for pulmonary embolism in pregnant and postpartum women?

Pulmonary embolism (PE) is a leading cause of death in pregnancy and postpartum. Clinicians face a difficult choice when deciding whether to use diagnostic imaging to investigate for suspected PE in these patients, between risking potentially catastrophic consequences of missed diagnosis if imaging is withheld and risking unnecessary iatrogenic harm to both mother and fetus if imaging is overused. This paper explores the options for imaging and evidence for the use of clinical features, clinical predictions scores or biomarkers to select pregnant and postpartum women for imaging. It also considers where future research could be most appropriately directed.

Age and sex-dependent trends in pulmonary embolism testing and derivation of a clinical decision rule for young patients.

IMPORTANCE: Despite low prevalence of pulmonary embolism (PE) in young adults, they are frequently imaged for PE, which involves radiation exposure and substantial financial cost. OBJECTIVE: Determine the use and positive proportions for PE imaging by age, differences in clinical presentation of PE by age and the projected impact of an age-targeted decision rule. DESIGN: Analysis of two national population-based datasets: the 2009 Nationwide Emergency Department Sample, a 20% sample of US emergency departments (EDs) and the 2003-2006 Pulmonary Embolism Rule-out Criteria (PERC) dataset, a multisite cohort of ED patients with suspected PE from 12 US EDs. RESULTS: Prevalence of PE was 10 times lower in young patients (18-35 years) than in older patients (>65 years) (0.06% vs 0.60%, p<0.001), but young patients were imaged for PE almost as frequently as older patients (2.3% vs 3.2%). This resulted in a lower proportion of positive examinations in young adults than older adults (2.3% vs 17.4%, p<0.001 in women; 4.0% vs 21.4%, p<0.001 in men). Clinical predictors of PE varied by age. Tachycardia was a significant predictor of PE in older patients (OR: 1.2-1.9, p<0.001), but not young patients. Fever was a significant predictor only in young patients (OR: 1.4-7.2, p<0.01). A modification of the previously described PERC rule to include age-specific risk factors could reduce PE imaging by 51% in young patients, with a missed PE rate of 0.6% in those excluded from imaging. CONCLUSIONS AND RELEVANCE: Young patients are frequently imaged for PE and have lower positive imaging rates than older patients. After further validation, application of our proposed rule for excluding young patients from PE imaging could reduce imaging, increase the positive rate of imaging and result in a low rate of missed PE among those excluded from imaging.

Atrial fibrillation in acute pulmonary embolism: prognostic considerations.

AIMS: Although it is accepted that atrial fibrillation (AF) may be both the contributing factor and the consequence of pulmonary embolism (PE), data on the prognostic role of AF in patients with acute venous thromboembolism are scarce. Our aim was to study whether AF had a prognostic role in patients with acute PE. METHODS: Retrospective cohort study involving 270 patients admitted for acute PE. Collected data: past medical history, analytic/gasometric parameters, admission ECG and echocardiogram, thoracic CT angiography. Patients followed for 6 months. An analysis was performed in order to clarify whether history of AF, irrespective of its timing, helps predict intrahospital, 1-month and 6-month all-cause mortality. RESULTS: Patients with history of AF, irrespective of its timing (n=57, 21.4%), had higher intrahospital (22.8% vs 13.1%, p=0.052, OR 2.07, 95% CI 0.98 to 4.35), 1-month (35.1% vs 16.9%, p=0.001, OR 3.16, 95% CI 1.61 to 6.21) and 6-month (45.6% vs 17.4%, p<0.001, OR 4.67, 95% CI 2.37 to 9.21) death rates. The prognostic power of AF was independent of age, NT-proBNP values, renal function and admission blood pressure and heart rate and additive to mortality prediction ability of simplified PESI (AF: p=0.021, OR 2.31, CI 95% 1.13 to 4.69; simplified PESI: p=0.002, OR 1.47, CI 95% 1.15 to 1.89). The presence of AF at admission added prognostic value to previous history of AF in terms of 1-month and 6-month all-cause mortality prediction, although it did not increase risk for intrahospital mortality. CONCLUSIONS: The presence of AF, irrespective of its timing, may independently predict mortality in patients with acute PE. These data should be tested and validated in prospective studies using larger cohorts.

Multiple Venous Thromboses and Renal Failure in Behcet's Disease: A Case Report and Review of the Literature.

Behcet's disease (BD) is a systemic condition of unknown etiology, characterized by a wide clinical polymorphism. Vascular involvement in BD is rare and can be revealing in many cases. We present an advanced case of BD with multiple venous thromboses associated with urgent dialysis-dependent end-stage chronic renal failure. This case highlights the complexity of managing BD, emphasizing the challenges associated with multiple thromboses and the crucial importance of early diagnosis to optimize the management of this systemic disease.

Transfer of patients with ruptured abdominal aortic aneurysm from general hospitals to specialist vascular centres: results of a Delphi consensus study.

AIM: To explore areas of consensus and disagreement concerning the interhospital transfer of patients with a clinical diagnosis of ruptured abdominal aortic aneurysm. METHODS: A three-round Delphi questionnaire approach was used among vascular and endovascular surgery and emergency medicine specialists to explore patient characteristics and clinical management issues for emergency interhospital transfer. Analysis is based on 38 responses to rounds 2 and 3 (19 vascular surgeons, 6 interventional radiologists, 13 emergency care specialists) with agreement reported when 70% of respondents were in agreement. RESULTS: Initially there was agreement that transfer patients should be <85 years of age, either alert or with fluctuating consciousness, with moderate or minimal systemic disease, needing no/some help with daily living. Round 3 clarified that patients requiring inotropes and those institutionalised for mental infirmity should be transferred. Those with cardiac arrest in current episode should not be transferred. There was no agreement as to whether those institutionalised with physical infirmities, unconscious/intubated patients or those with severe systemic disease should be transferred. Speed was accepted as important, with agreement for specialty trainees to arrange transfer if consultants were not on site. Consultant-consultant discussion was recommended for patients with severe systemic disease. CT confirmation of diagnosis was considered unnecessary before transfer but ultrasound assessment was desirable, and transfers should not be delayed by waiting for specific tests. There was no agreement about blood tests and ECG before transfer or whether blood should accompany the patient being transferred. There was no agreement as to whether specific staff/facilities needed to be in place at the specialist hospital. A systolic blood pressure ≥70 mm Hg was sufficient for transfer without the need for intravenous fluids unless deterioration occurred. CONCLUSIONS: There is broad agreement about the type of patient who should be eligible for transfer but disagreements about patient management before and during transfer remain.