Excluding pulmonary embolism at the bedside with low pre-test probability and D-dimer: safety and clinical utility of 4 methods to assign pre-test probability

INTRODUCTION: Less than 35% of patients suspected of having pulmonary embolism (PE) actually have PE. Safe bedside methods to exclude PE could save scarce health care resources if they exclude large proportions of patients with suspected PE and are widely applicable. Non-Elisa D-dimer in combination with pre-test probability of suspected PE can safely exclude PE at the bedside. Pre-test probability can be assigned by gestalt or by using clinical models (Wells, Wicki, Rodger). MATERIALS AND METHODS: We combined two databases from studies of patients with suspected PE and retrospectively compared the diagnostic test characteristics of the different methods of assigning pre-test probability. RESULTS: 535 patients were studied. PE was confirmed in 20.8% of study patients. Two clinical predictive models (Rodger and Wells) and overall diagnostic impression have similar sensitivities ranging from 96% (95% confidence interval (CI) 89-99%) to 99% (93-100%). Wicki's model has a sensitivity of 89% (77-96%). The Wells' model with a cutoff of less than 2 points in association with semi-quantitative D-dimer has a specificity of 11% (CI 7-15%). The specificities for the other clinical predictive model are ranging from 21% (17-25%) to 49% (CI 42-55%). CONCLUSION: Semi-quantitative D-dimer must be combined with safe clinical probability assessment to safely exclude PE in a significant proportion of patients. Wicki's model in association with semi-quantitative D-dimer has the lowest sensitivity and should be used carefully to exclude PE at the bedside. The Wells' model with a cutoff of less than 2 points when combined with semi-quantitative D-dimer excluded very few patients and therefore limits its clinical utility.     

D-dimer and TAT measurement in patients with deep venous thrombosis: utility in diagnosis and judgement of anticoagulant treatment effectiveness

The plasma levels of thrombin-antithrombin III-complexes (TAT) and the fibrin split product D-Dimer were measured in 39 patients with phlebographically proven acute DVT: 34 patients had proximal DVT, 5 had calf DVT. The sensitivity of D-Dimer and TAT measurements in the diagnosis of proximal DVT was found to be dependent on the duration of symptoms: 0 to 7 days (n = 27): elevated D-Dimer levels (greater than 120 ng/ml) = 1, D-Dimer Latex test positive (greater than 500 ng/ml) = 1, elevated TAT levels (greater than 6 ng/ml) = 0.88. Eight to 14 days (n = 7): elevated D-Dimer levels = 1, D-Dimer Latex test positive = 0.33, elevated TAT levels = 0.66; specificity: elevated D-Dimer: 0.48, D-Dimer Latex test: 1, elevated TAT: 0.76. Calf DVT patients (n = 5) had elevated D-Dimer levels, negative Latex tests and 3 of them had normal TAT values. Hemostatic and fibrinolytic parameters were also determined in 13 patients during heparin treatment of proximal DVT. Elevated D-Dimer and TAT levels rapidly decreased after initiation of anticoagulant therapy. In 2 of 13 patients a marked increase in D-Dimer and TAT levels was observed in periods of ineffective heparinization, documented by normal or only slightly prolonged thrombin clotting times. We conclude from our results that 1) D-Dimer EIA measurement, in contrast to TAT measurement, shows a very high sensitivity in the diagnosis of DVT, 2) due to low specificity this test can only be used to exclude thrombosis in patients with suspected DVT, and 3) the determination of the plasma levels of D-Dimer and TAT may be useful for judging the effect of anticoagulant treatment on thrombotic processes.     

Exclusion of deep venous thrombosis with D-dimer testing--comparison of 13 D-dimer methods in 99 outpatients suspected of deep venous thrombosis using venography as reference standard

In a direct assay comparison we evaluated the diagnostic performance of 10 novel D-Dimer assays for the exclusion of deep venous thrombosis (DVT). In addition, 3 conventional ELISA D-Dimer assays were included as reference tests. The study was performed in 99 consecutive outpatients referred to the emergency department for clinical suspicion of DVT. Venography was used as reference standard and demonstrated the presence of DVT in 50 patients (6 patients with isolated distal DVT and 44 patients with proximal DVT). The qualitative D-Dimer assays Minutex and SimpliRED and the quantitative BC DD showed overall sensitivities (for proximal and distal DVT) of only 80-83% with specificities that ranged from 87 to 94%. Overall sensitivity was 94% for the qualitative INSTANT I.A. and 98% for the quantitative Turbiquant at a cut-off level equal to the detection limit. Using different cut-off levels a sensitivity of 100% for proximal DVT and for proximal as well as distal DVT could be obtained for NycoCard, IL DD, Liatest, Tinaquant and VIDAS D-Dimer assays with specificities that ranged from 31% (NycoCard) to 71% (VIDAS) for proximal DVT and from 12% (NycoCard) to 47% (IL DD) for overall DVT. At a cut-off level equal to the upper limit of the reference range only Tinaquant and VIDAS showed a sensitivity of 100% for proximal as well as for distal DVT with a specificity of 39% and 41% respectively. The results of this study suggest that the VIDAS and Tinaquant D-Dimer assays have the highest sensitivity for the exclusion of DVT in outpatients. In outpatients that have a low or moderate pretest probability for DVT, these tests may be used in management studies where anticoagulation is withheld on the basis of D-Dimer testing alone.     

Rapid D-dimer test combined a clinical model for deep vein thrombosis. Validation with ultrasonography and clinical follow-up in 383 patients

An optimal approach to the diagnosis of deep vein thrombosis (DVT) in lower limbs in the emergency department is still unknown. In this prospective cohort study, we aimed to evaluate the accuracy of the widely available plasma D-dimer test (VIDAS) and establish the usefulness of combining D-dimer testing with a clinical model to reduce the need for serial ultra-sonographies and improve the diagnostic strategy of DVT. We performed a cohort study in 383 consecutive outpatients referred to the emergency department of Hospital La Princesa, with clinical suspicion of DVT. The patients were stratified into three pre-test probability categories using an explicit clinical model (Wells score), and underwent a quantitative automated ELISA D-dimer assay (VIDAS D-Dimer bioMérieux). Patients were managed according to the diagnostic strategy based on clinical probability and compression ultrasonography (CU). Patients for whom DVT was considered a high pre-test probability with negative ultrasonographic findings in the initial CU, returned the following week for repeat ultrasonography. All patients with DVT excluded did not receive anticoagulant therapy, and were followed up for three months to monitor the development of venous thromboembolic complications. DVT was confirmed in 102 patients (26.6%): 95 in the initial test, four in the second test, and three who developed venous thromboembolic complications in the three-month follow-up period. The calculated D-dimer cut-off level was 1 micro g/ml. One hundred patients (98%) with DVT had positive D-dimer. D-dimer had a sensitivity of 98% and a negative predictive value of 98.6%. Among the high-probability patients with positive D-dimer tests and initial negative CU, 9.75% had DVT on repeat CU at one week. The study results suggest that the addition of VIDAS D-dimer to this diagnostic algorithm could improve the management of patients with suspected DVT in daily practice. A diagnostic approach of DVT based on D-dimer (cut-off > or =1 microg/ml) as the first diagnostic tool for the exclusion of DVT, and the clinical probability model as the tool that identifies those patients requiring a second ultrasonography is useful and suitable for daily medical practice.     

Accuracy and usefulness of a clinical prediction rule and D-dimer testing in excluding deep vein thrombosis in cancer patients

Introduction

Deep vein thrombosis (DVT) can be safely and reliably excluded in patients with a low clinical probability and a negative D-dimer result but the accuracy and utility of such a strategy is less certain in cancer patients. We sough to compare the performance of the Wells pretest probability (PTP) model and D-dimer testing between patients with and without cancer and to examine the utility of the two PTP model classification schemes (low/moderate/high versus unlikely/likely) in excluding DVT in patients with cancer.

Materials and methods

Pooled analysis of databases from three prospective diagnostic studies evaluating consecutive outpatients with suspected DVT.

Results

A total of 2696 patients were evaluated. DVT was diagnosed in 403 (15%) patients overall and in 83 of 200 (41.5%) cancer patients. The PTP distribution and the prevalence of DVT in each PTP category were significantly different between patients with and without cancer, regardless of the classification used (p < 0.01). In patients with cancer, the negative predictive values of a low or unlikely PTP score in combination with a negative D-dimer result were 100% (95% CI 69.8%-100%) and 100% (95% CI 82.8%-96.6%), respectively. However, the specificities ranged from 46.2% (95%CI 27.1%-66.3%) to 57.1% (95%CI 41.1%-71.9%). Further testing was required in 94% of cancer patients using the low/moderate/high PTP classification and in 88% using the unlikely/likely stratification.

Conclusions

As in patients without cancer, the combination of a low or unlikely PTP with a negative D-dimer result can exclude DVT in patients with cancer. However, this strategy has limited utility because very few cancer patients present with this combination.     

Combined use of D-dimer and P-selectin for the diagnosis of splenic or portal vein thrombosis following splenectomy

To investigate the predictive value of combined use of D-dimer and P-selectin for splenic or portal vein thrombosis (SPVT) after splenectomy. A prospective study was carried out in 82 patients who had undergone splenectomy for portal hypertension secondary to hepatic cirrhosis. Plasma levels D-dimer and P-selectin were measured before and after the surgery.27 (30.1%) patients developed SPVT following the portal hypertension surgery. The post-operative D-dimer and P-selectin levels in patients with SPVT were significantly higher than in those without PVT (n = 55, P < 0.01). The receiver-operated characteristics curves (ROC) of D-dimer and P-selectin showed a significant predictive value in SPVT (D-dimer, Az = 0.880, P < 0.01; P-slectin, Az = 0.933, P < 0.01). The sensitivity and specificity of D-dimer (> 500 µg/mL) in diagnosing SPVT were 88.9% and 78.2% respectively. P-selectin > 90 ng/mL had an 85.2% sensitivity and 85.5% specificity for SPVT. The combination of the D-dimer and P-selectin criteria yielded an 82.0% sensitivity and 97.6% specificity for SPVT. In Conclusion, there was a significant elevation in plasma D-dimer and P-selectin in patients with post-operative SPVT. A combination of plasma D-dimer and P-selectin may be used as biomarkers to screen or diagnose SPVT following splenectomy.     

Clinical probability assessment and D-dimer determination in patients with suspected deep vein thrombosis, a prospective multicenter management study

Objectives

To investigate the reliability of a combined strategy of clinical assessment score followed by a local D-dimer test to exclude deep vein thrombosis. For comparison D-dimer was analysed post hoc and batchwise at a coagulation laboratory.

Design

Prospective multicenter management study.

Setting

Seven hospitals in southern Sweden.

Subjects

357 patients with a suspected first episode of deep vein thrombosis (DVT) were prospectively recruited and pre-test probability score (Wells score) was estimated by the emergency physician. If categorized as low pre-test probability, D-dimer was analysed and if negative, DVT was considered to be ruled out. The primary outcome was recurrent venous thromboembolism (VTE) during 3 months of follow up.

Results

Prevalence of DVT was 23.5% (84/357). A low pre-test probability and a negative D-dimer result at inclusion was found in 31% (110/357) of the patients of whom one (0.9%, [95% CI 0.02-4.96]) had a VTE at follow up. Sensitivity, specificity, negative predictive value and negative likelihood ratio for our local D-dimer test in the low probability group were 85.7%, 74.5%, 98.2%, and 0,19 respectively compared to 85.6%, 67,6%, 97.9% and 0,23 using batchwise analysis at a coagulation laboratory.

Conclusion

Pre-test probability score and D-dimer safely rule out DVT in about 30% of outpatients with a suspected first episode of DVT. One out of 110 patients was diagnosed with DVT during follow up. No significant difference in diagnostic performance was seen between local D-dimer test and the post hoc batch analysis with the same reagent in the low probability group.     

Comparative evaluation of D-dimer assays for exclusion of deep venous thrombosis in symptomatic outpatients

Diagnostic work-up of patients sent to the hospital for diagnosing of deep venous thrombosis (DVT) often combines the determination of D-dimer and the application of a clinical probability score. To fulfill diagnostic as well as economic needs, D-dimer assays should exhibit a high negative predictive value (NPV) as well as reasonable specificity. In this study, we evaluated both a latex-enhanced immunoassay for use on routine coagulation analyzers and a radial partition immunoassay (RPIA) for use on a point-of-care analyzer. Samples included were from 344 outpatients with suspected deep venous thrombosis. Among them, 100 had deep venous thrombosis. Results obtained for both assays show a good efficiency for exclusion of deep venous thrombosis with well-acceptable specificity.     

Doppler ultrasonography screening of poor-grade subarachnoid hemorrhage patients increases the diagnosis of deep venous thrombosis

Abstract

Background: Prophylactic anticoagulation greatly decreases the prevalence of deep venous thrombosis (DVT) in neurosurgical patients. Using Doppler ultrasonography (USG), recent studies demonstrate a 1% DVT detection rate following microsurgery or endovascular treatment for aneurysmal subarachnoid hemorrhage (aSAH). We hypothesize that reported statistics underestimate the DVT detection rate in this high risk cohort by accounting for only symptomatic thromboses. This study utilizes Doppler USG to examine the prevalence of DVT in a large population of aSAH patients and attempts to identify a high-risk subgroup within this cohort.

Methods: We retrospectively examined 178 aSAH patients who underwent screening lower extremity Dopplers (LEDs) and 57 who did not undergo screening LEDs. All received pharmacologic and mechanical DVT prophylaxis. We analysed DVT prevalence within these two groups and compared rates to the literature. We then segregated patients according to Hunt–Hess grade and determined DVT prevalence within subgroups.

Results: Patients who underwent LED screening demonstrated a 3.4% (6/178) DVT rate, compared to 0% (0/57) in the unscreened cohort. Our screening protocol yielded a thrombosis rate almost triple that reported in the literature (3.4% versus 1.2%). A significantly greater (p<0.05) percentage of screened Hunt–Hess III–V patients (6.5%, 6/93) had positive LEDs compared to Hunt–Hess I–II patients (0%, 0/85).

Conclusion: These data suggest that while pharmacologic prophylaxis lowers the prevalence of symptomatic DVTs in aSAH patients, the number of asymptomatic DVTs remains significant, particularly in patients with formidable neurological deficits. While a formal cost-effective analysis is warranted, our data suggest that screening high-risk patients may increase the diagnosis of asymptomatic DVTs and potentially prevent serious medical complications.     

Different characteristics and prognostic impact of deep-vein thrombosis / pulmonary embolism and intraabdominal venous thrombosis in colorectal cancer patients

This study was performed to determine the incidence, risk factors, and prognostic implications of venous thromboembolism (VTE) in Asian patients with colorectal cancer (CRC). Differences in clinical characteristics and prognostic impact between extremity venous thrombosis (or deep-vein thrombosis; DVT)/pulmonary embolism (PE) and intra-abdominal venous thrombosis (IVT) were also evaluated. For this study, consecutive CRC patients (N = 2,006) were enrolled and analyses were conducted retrospectively. VTEs were classified into two categories (DVT/PE and IVT). Significant predictors of developing VTEs were advanced stage and an increased number of co-morbidities. The two-year cumulative incidence of DVT/PE was 0.3%, 0.9% and 1.4% in stages 0~1, 2 and 3, respectively; this incidence range of DVT/PE in Asian patients with loco-regional CRC was lower than in Western patients. However, the two-year incidence (6.4%) of DVT/PE in Asian patients with distant metastases was not lower than in Western patients. Although 65.2% of patients with DVT/PE were symptomatic, only 15.7% of patients with IVT were symptomatic. During chemotherapy, DVT/PE developed more frequently than IVT. Only DVT/PE had a negative effect on survival; IVT had no prognostic significance. In conclusion, despite the low incidence of DVT/PE in Asian patients with loco-regional CRC, the protective effect of Asian ethnicity on VTE development disappears as tumour stage increases in patients with distant metastases. Considering different clinical characteristics and prognostic influences between DVT/PE and IVT, the treatment approach should be also different.     

Diagnostic value of the Nycocard, Nycomed D-dimer assay for the diagnosis of deep venous thrombosis and pulmonary embolism: a retrospective study

The relatively new D-dimer assay from Nycomed Pharma (Nycocard), which has shown both high sensitivity and specificity in diagnosing deep venous thrombosis (DVT) and pulmonary embolism (PE) in earlier studies, was re-evaluated retrospectively. The diagnostic value of the D-dimer assay for DVT was evaluated with contrast venography as reference. The diagnostic value of the D-dimer assay for PE was evaluated with pulmonary scintigraphy as reference. D-dimer tests were examined from 54 consecutive patients. The D-dimer assay was found to have a sensitivity and specificity of 50% and 58%, respectively, for the diagnosis of DVT, with a positive predictive value (PPV) and negative predictive value (NPV) of 55% and 54%, respectively. Using reference diagnostic results of high probability and low probability for the diagnosis of PE, the D-dimer test sensitivity and specificity was found to be 40% and 94%, respectively (PPV: 86%, NPV: 64%). The diagnostic value of the Nycocard(R) assay appears to be very limited for the diagnosis of DVT and PE. This retrospective study suggests that it is unsuitable as a screening method. Further re-evaluation of D-dimer assays is recommended prior to routine clinical use.     

Cerebral cortical and deep venous thrombosis without sinus thrombosis: clinical MRI correlates

BACKGROUND: Cortical and/or deep vein thrombosis (CDVT) without dural sinus involvement is uncommon and presents diagnostic difficulty for many reasons. Our aim is to determine the relationship between magnetic resonance imaging (MRI) findings and clinical findings in patients with CDVT. METHODS: Forty-six patients with venous stroke proved on MRI included in our Registry, corresponding to 0.1% of 4650 patients with stroke, were studied. Magnetic resonance angiography (MRA) was performed in all patients, and 18 of them had follow-up MRA. Outcome was evaluated by using the Glasgow Outcome Scale at the time of discharge and during follow-up. RESULTS: Thirty-two patients presented cortical venous stroke; 21 of them had involvement of the dorsomedial venous system, six had a defect in the posteroinferior venous group, and five had a defect in the anteroinferior venous group. Thirteen patients presented simultaneous involvement of the superficial and deep venous system; seven with a defect in the parietal and internal cerebral veins (three with involvement of vein of Gallen), four with a defect in the temporooccipital (vein of Labbé) and basal vein of Rosenthal, two with a deficit in the anterior frontotemporal and uncal-pterygoid venous system. One patient had deep venous thrombosis primarily localized to the thalami bilaterally and the basal ganglia on the right because of occlusion of the thalamostriate veins. The main presenting symptoms of CDVT were headache, focal neurologic signs, partial complex or secondary generalized seizures, and consciousness disturbances in those with deep venous thrombosis, presented alone or in combination at onset. CDVT was more than twofold more frequent in women than in men. Pregnancy, puerperium, oral contraceptive use, and infections were the most common predisposing factors. CONCLUSION: Computerized tomography, conventional MRI and diffusion-weighted imaging showing ischemic and/or hemorrhagic lesion that does not follow the boundary of classical arterial boundaries without signs of sinus thrombosis, and partial or generalized seizures followed by focal neurologic signs may predict CDVT. The outcome of patients with cortical venous stroke was good, but not in those with cortical plus deep venous infarction.     

A systematic review of the accuracy of ultrasound in the diagnosis of deep venous thrombosis in asymptomatic patients

Evaluation of the accuracy of ultrasound has yielded heterogeneous results. Our objective was to summarize the evidence on the accuracy of ultrasound compared to venography in asymptomatic patients, taking into account the variation due to threshold differences. Searches of journal table of contents, computer databases (Medline, Embase, Biomed, Cochrane) and conference proceedings were performed. A study was eligible if it prospectively compared ultrasound to venography for the diagnosis of DVT in asymptomatic patients. Data of studies selected for inclusion were extracted independently by two authors. High quality studies with consecutive patient enrollment, blind evaluation of the two techniques, and absence of verification bias are summarized as Level 1, while those not fulfilling one or more of these criteria are considered Level 2. Original study authors were contacted to confirm accuracy and to provide missing data. A pooled estimate of the accuracy of ultrasound was obtained according to the method of Moses and coworkers. This method gives a summary diagnostic odds ratio (DOR). The DOR is a single indicator of test performance. It varies between 0 and infinity and exceeds 1, only when ultrasound is more often positive in patients with DVT relative to those without DVT. Higher DOR indicates better discriminatory test performance. Thirty one studies were rated as potentially unbiased and graded as Level 1. The mean prevalence of DVT as determined by venography was 22%. In Level 1 studies, the odds of positive ultrasound in proximal veins was 379 times higher (95% confidence limits 65, 2,200) and in distal veins 32 times higher (7.5, 135) among patients with DVT than those without. Our results suggest that, particularly for proximal veins, ultrasound is accurate for the diagnosis of DVT in asymptomatic postoperative orthopedic patients. More research is needed in other clinical settings.     

颅内静脉窦血栓形成患者纤维蛋白原D-二聚体与预后的相关性

目的探讨静脉窦血栓形成(CVST)患者纤维蛋白原、D-二聚体与短期预后的关系。方法选取CVST患者56例为CVST组,检测血浆纤维蛋白原、D-二聚体,并与50例健康者(对照组)作对照。按改良Rankin量表(mRS)评分,将CVST患者再分为预后良好组和预后不良组,并对比2组纤维蛋白原、D-二聚体水平。结果静脉窦血栓形成患者组D-D、Fbg分别为(316.37±14.59)ng/mL、(4.96±1.27)g/L,均显著高于对照组;预后良好组D-D、Fbg分别为(289.34±22.37)ng/mL、(4.58±1.16)g/L,均显著低于CVST预后不良组。结论血浆纤维蛋白原、D-二聚体对于CVST的诊断和短期预后判断有重要临床价值。     

Residual venous obstruction in patients with a single episode of deep vein thrombosis and in patients with recurrent deep vein thrombosis

Residual venous obstruction (RVO) in patients with previous deep vein thrombosis (DVT) of the lower limbs has been suggested as an independent risk factor for recurrent venous thromboembolism (VTE). RVO could be a marker of a persistent prothrombotic state. We have compared the rate of RVO in patients with DVT and a personal history of at least one previous episode of VTE to the rate of RVO among patients with a first episode of DVT. All patients underwent compression ultrasonography (CUS) of the lower limbs 1 year after index DVT. RVO was arbitrarily defined as a thrombus occupying, at maximal compressibility, more than 20% of the vein area in the absence of compression. 50 consecutive patients with recurrent DVT and 50 age and sex-matched patients with a single episode of DVT were enrolled. The index event was idiopathic in 62% of patients with recurrent DVT and in 60% of patients with a single episode. In 74% of patients with recurrent DVT the index event occurred in either the contralateral leg or in a different segment of the ipsilateral leg. RVO was detected in 50% of patients with a single episode of DVT and in 88% of patients with recurrent DVT (p<0.00001). The prevalence of RVO is significantly higher in patients with recurrent DVT than in patients with a single episode. This finding supports the importance of RVO as a potential marker of a persistent prothrombotic state.     

Ruling out deep venous thrombosis in primary care. A simple diagnostic algorithm including D-dimer testing

In primary care, the physician has to decide which patients have to be referred for further diagnostic work-up. At present, only in 20% to 30% of the referred patients the diagnosis DVT is confirmed. This puts a burden on both patients and health care budgets. The question arises whether the diagnostic work-up and referral of patients suspected of DVT in primary care could be more efficient. A simple diagnostic decision rule developed in primary care is required to safely exclude the presence of DVT in patients suspected of DVT, without the need for referral. In a cross-sectional study, we investigated the data of 1295 consecutive patients consulting their primary care physician with symptoms suggestive of DVT, to develop and validate a simple diagnostic decision rule to safely exclude the presence of DVT. Independent diagnostic indicators of the presence of DVT were male gender, oral contraceptive use, presence of malignancy, recent surgery, absence of leg trauma, vein distension, calf difference and D-dimer test result. Application of this rule could reduce the number of referrals by at least 23% while only 0.7% of the patients with a DVT would not be referred. We conclude that by using eight simple diagnostic indicators from patient history, physical examination and the result of D-dimer testing, it is possible to safely rule out DVT in a large number of patients in primary care, reducing unnecessary patient burden and health care costs.