Investigation of age-adjusted D-dimer using an uncommon assay

BackgroundUse of an age-adjusted D-dimer for the evaluation of acute pulmonary embolus (PE) has been prospectively validated in the literature and has become a practice recommendation from major medical societies. Most research on this subject involves the most common D-dimer assays reporting in Fibrinogen Equivalent Units (FEU) with a non-age-adjusted manufacturer-recommended cutoff of 500 ng/ml FEU. Limited research to date has evaluated age-adjustment in assays that report in D-Dimer Units (D-DU), which use a manufacturer-recommended cutoff of 230 ng/ml D-DU. Despite scant evidence, an age-adjusted formula using D-DU has been recently endorsed by the American College of Emergency Physicians (ACEP). This formula seems arbitrary in its derivation and unnecessarily deviates from existing thresholds, thus prompting the creation of our novel-age adjustment formula. The goal of this study was to retrospectively evaluate the test characteristics of our novel age-adjusted D-dimer formula using the D-DU assay in comparison to existing traditional and age-adjusted D-dimer thresholds for the evaluation of acute PE in the ED.MethodsThis was a retrospective chart review at an academic quaternary health system with three EDs and 195,000 combined annual ED visits. Only patients with D-dimer testing and CT PE protocol (CTPE) imaging were included. Admission and discharge diagnosis codes were used to identify acute PE. Outcome measures were sensitivity, specificity, negative predictive value (NPV) and positive predictive value (PPV) of an unadjusted traditional threshold (230) compared with both novel and ACEP-endorsed age adjusted thresholds, (Age × 5) ? 20 and Age × 5 if >50, respectively. Estimates with their exact 95% threshold were performed.Results4846 adult patients were evaluated from January 2012 to July 2017. Group characteristics include a mean age of 52 and a frequency of acute PE diagnosis by CTPE of 8.25%. Traditional D-dimer cutoff demonstrated a sensitivity of 99.8% (95% CI 98.6–100), specificity of 16.7% (95% CI 15.6–17.8) and NPV of 99.9% (95% CI 99.3–100). Our novel age-adjusted D-dimer thresholds had a sensitivity of 97.0% (95% CI 94.8–98.4), specificity of 27.9% (95% CI 26.6–29.2) and NPV of 99.0% (95% CI 98.3–99.5) with the ACEP-endorsed formula demonstrating similar test characteristics.ConclusionUse of an age-adjusted D-dimer on appropriately selected patients being evaluated for acute PE in the ED with a D-DU assay increases specificity while maintaining a high sensitivity and NPV. Both our novel formula and the ACEP-endorsed age-adjusted formula performed well, with our novel formula showing a trend towards improved testing characteristics.     

Combined use of clinical pretest probability and D-dimer test in cancer patients with clinically suspected deep venous thrombosis

BACKGROUND: The value of the D-dimer (DD) test in combination with the clinical pretest probability (PTP) has not been evaluated in cancer patients with suspected deep vein thrombosis (DVT), whereas this group of patients usually accounts for 10-25% of clinically suspected DVT. METHODS: A cohort of 2066 consecutive patients with clinically suspected DVT was investigated. Patients were judged to be positive or negative for DVT according to the outcomes of serial compression ultrasound and a 3-month follow-up period with imaging test verification of the symptomatic cases. Diagnostic accuracy indices of the DD test according to the PTP score were assessed in patients with and without cancer. RESULTS: Of the cohort, 244 (11%) were known to have cancer at presentation. A venous thromboembolic event was diagnosed in 41% of the patients with cancer and in 22% of the patients without malignancy. Among the cancer patients, 17% were considered to have a low PTP, 35% a moderate and 41% a high PTP. The negative predictive value (NPV) of the DD test was 100% (95% CI, 85-100) and 97% (95% CI, 88-99) among cancer patients with low PTP or low-moderate PTP. In the absence of malignancy, the corresponding NPV were 98% and 97%, respectively. The specificity of the DD test progressively decreased moving from the low to the higher PTP. CONCLUSIONS: In cancer patients with clinically suspected DVT, a negative DD might be useful in excluding the diagnosis within the low or low-moderate PTP groups. More studies are warranted to confirm these findings.     

Sensitivity and specificity of the semiquantitative latex agglutination D-dimer assay for the diagnosis of acute pulmonary embolism as defined by computed tomographic angiography

OBJECTIVE: To determine the sensitivity and specificity of the semiquantitative latex agglutination plasma fibrin D-dimer assay for the diagnosis of acute pulmonary embolism by using computed tomographic (CT) angiography as the diagnostic reference standard. PATIENTS AND METHODS: From January 1, 1998, to June 26, 2000, patients who had both semiquantitative latex agglutination plasma fibrin D-dimer testing and CT angiography for suspected acute pulmonary embolism were selected for the study. A D-dimer value greater than 250 ng/mL was considered positive for thromboembolic disease. Diagnosis of acute pulmonary embolism was based solely on the interpretation of the CT angiogram. The D-dimer assay results were then compared with the CT angiographic diagnoses. RESULTS: Of 946 CT studies, 172 (18%) were positive for acute pulmonary embolism. The D-dimer assay was positive for 612 (65%) of the 946 patients. For acute pulmonary embolism, the D-dimer assay had a sensitivity of 0.83 (95% confidence interval [CI], 0.76-0.88), a specificity of 039 (95% CI, 036-0.43), a negative likelihood ratio of 0.44 (95 % CI, 032-0.62), and a negative predictive value of 0.91 (95% CI, 0.87-0.94). CONCLUSIONS: The semiquantitative latex agglutination plasma fibrin D-dimer assay had moderate sensitivity and low specificity for the diagnosis of acute pulmonary embolism. When used alone, the results of this test were insufficient to exclude this serious and potentially fatal disorder. Approximately two thirds of our patients had positive D-dimer assays and required further evaluation to exclude acute pulmonary embolism.     

Tandem measurement of D-dimer and myeloperoxidase or C-reactive protein to effectively screen for pulmonary embolism in the emergency department

OBJECTIVES: The hypothesis was that the tandem measurement of D-dimer and myeloperoxidase (MPO) or C-reactive protein (CRP) could significantly decrease unnecessary pulmonary vascular imaging in emergency department (ED) patients evaluated for pulmonary embolism (PE) compared to D-dimer alone. METHODS: The authors measured the sequential combinations of D-dimer and MPO and D-dimer and CRP in a prospective sample of ED patients evaluated for PE at two centers. Patients were followed for 90 days for venous thromboembolism (VTE, either PE or deep venous thrombosis [DVT]), which required the consensus of two of three blinded physician reviewers. RESULTS: The authors enrolled 304 patients, 22 with VTE (7%; 95% confidence interval [CI] = 5% to 10%). The sensitivity and specificity of a D-dimer alone (cutoff > or = 500 ng/mL) were 100% (95% CI = 85% to 100%) and 59% (95% CI = 53% to 65%), respectively, and was followed by pulmonary vascular imaging negative for PE in 38% (115/304; 95% CI = 32% to 44%). The combination of either a negative D-dimer, or MPO < 22 mg/dL, had a sensitivity of 100% and specificity of 73% (95% CI = 67% to 78%). Thus, tandem measurement of D-dimer and MPO would have decreased the frequency of subsequent negative pulmonary vascular imaging from 38% to 25% (95% CI of the difference of -13% = -5% to -20%). The combination of CRP and D-dimer would not have significantly improved the rate of negative imaging. CONCLUSIONS: The tandem measurement of D-dimer and MPO would have significantly decreased negative pulmonary vascular imaging compared with D-dimer alone and should be validated prospectively.     

The post-thrombotic syndrome: risk factors and impact on the course of thrombotic disease

BACKGROUND: The post-thrombotic syndrome (PTS) is a frequent complication of deep vein thrombosis (DVT). Patients with recurrent ipsilateral DVT have an increased risk of PTS; other risk factors are unknown. OBJECTIVES: To establish risk factors of PTS and its impact on venous thrombotic disease. PATIENTS: We prospectively followed 406 patients after a first symptomatic DVT for a median of 60 months. Patients with recurrent DVT, a natural inhibitor deficiency, the lupus anticoagulant, cancer, long-term anticoagulation, an observation time < 18 months and DVT-recurrence prior PTS-assessment were excluded. Study outcomes were occurrence of PTS and recurrent symptomatic DVT. RESULTS: PTS was assessed after 44 +/- 23 months (mean +/- SD) using a clinical classification score. PTS developed in 176 of 406 patients (43.3%). Severe PTS was rare (1.4%). Proximal DVT was the strongest risk factor of PTS [odds ratio (OR) 2.1, 95% confidence interval (CI) 1.3-3.7]. Male gender (OR 1.6, 95% CI 1.0-2.8) and elevated D-dimer levels (OR 1.9, 95% CI 1.0-3.9) were weaker risk factors. Factor V Leiden, factor II G20210A or high factor VIII did not confer an increased risk of PTS. At 4 years, the cumulative probability of recurrence was 7.4% (95% CI 3.2-11.7) among patients with PTS when compared with 1.6% (95% CI 0-3.5; P < 0.02) among patients without PTS. The risk of recurrence was 2.6-fold (95% CI 1.2-5.9) increased when PTS was present. CONCLUSIONS: Proximal DVT, male gender, and high D-dimer levels are independently associated with the development of PTS in patients with a first DVT. Patients with PTS have an increased risk of recurrent venous thromboembolism.     

Evaluation of a quantitative D-dimer latex immunoassay for acute pulmonary embolism diagnosed by computed tomographic angiography

OBJECTIVE: To determine the sensitivity and specificity of a quantitative plasma fibrin D-dimer latex immunoassay (LIA) for the diagnosis of acute pulmonary embolism. SUBJECTS AND METHODS: Study subjects were Mayo Clinic Rochester inpatients and outpatients with suspected acute pulmonary embolism; all had undergone quantitative D-dimer LIA testing and multidetector-row computed tomographic (CT) angiography between August 3, 2001, and November 10, 2003. Multidetector-row CT angiography was the diagnostic reference standard. RESULTS: Of 1355 CT studies, 208 (15%) were positive for acute pulmonary embolism. Median D-dimer levels were significantly higher for patients with acute pulmonary embolism (1425 ng/mL) than for patients without (500 ng/mL) (P<.001). The highest specificity that optimizes sensitivity for acute pulmonary embolism was achieved by using a discriminant value of 300 ng/mL, which yielded a sensitivity of 0.94 (95% confidence interval [CI], 0.89-0.97), a specificity of 0.27 (95% CI, 0.25-0.30), and a negative predictive value of 0.96 (95% CI, 0.93-0.98). CONCLUSION: The quantitative D-dimer LIA with a discriminant value of 300 ng/mL had high sensitivity and high negative predictive value but low specificity for the diagnosis of acute pulmonary embolism. On the basis of these results, we believe that a negative quantitative D-dimer LIA result and a low pretest probability of thromboembolism together are sufficient to exclude acute pulmonary embolism.     

Clinical probability and alveolar dead space measurement for suspected pulmonary embolism in patients with an abnormal D-dimer test result

BACKGROUND: Most patients with suspected pulmonary embolism (PE) have a positive D-dimer test and undergo diagnostic imaging. Additional non-invasive bedside tests are required to reduce the need for further diagnostic tests. OBJECTIVES: We aimed to determine whether a combination of clinical probability assessment and alveolar dead space fraction measurement can confirm or exclude PE in patients with an abnormal D-dimer test. METHODS: We assessed clinical probability of PE and alveolar dead space fraction in 270 consecutive in- and outpatients with suspected PE and positive D-dimer. An alveolar dead space fraction < 0.15 was considered normal. PE was subsequently excluded or confirmed by venous compression ultrasonography, spiral computed tomography and a 3-month follow-up. Radiologists were unaware of the results of clinical probability and capnography. RESULTS: PE was confirmed in 108 patients (40%). Capnography had a sensitivity of 68.5% (95% confidence interval [CI]: 58.9-77.1%) and a specificity of 81.5% (95% CI: 74.6-87.1%) for PE. Forty-five patients (16.6%) had both a low clinical probability and normal capnography (sensitivity: 99.1%, 95% CI: 94.9-100%) and 34 patients (12.6%) had both a high clinical probability and abnormal capnography (specificity: 100%, 95% CI: 97.7-100%). CONCLUSION: Capnography alone does not exclude PE accurately. The combination of clinical probability and capnography accurately excludes or confirms PE and avoids further testing in up to 30% of patients.     

Comparative study of transvaginal ultrasonography and CA 125 in the preoperative evaluation of myometrial invasion in endometrial carcinoma.

OBJECTIVE: To compare the ability of transvaginal sonography and serum CA 125 levels to predict myometrial invasion in patients with endometrial carcinoma. DESIGN AND METHODS: Prospective study in 50 consecutive patients (mean age 60 years, SD 10.5, range 29-77 years) diagnosed as having endometrial cancer and scheduled for surgical staging. All patients were evaluated by transvaginal ultrasonography. Endometrial thickness was measured in all cases and myometrial invasion was estimated as < 50% or > or = 50%. Serum CA 125 level was determined in each patient. A cut-off level of > or = 35 IU/ml was considered to predict myometrial invasion of > or = 50%. All patients underwent surgical staging, and definitive histopathological findings regarding myometrial invasion were used as the 'gold standard'. Sensitivity, specificity and positive predictive value (PPV) and negative predictive value (NPV) were calculated for transvaginal ultrasonography and CA 125 and compared. RESULTS: On histopathological analysis, myometrial invasion was found to be < 50% in 35 (70%) cases and > or = 50% in 15 cases (30%). Mean endometrial thickness in patients with superficial invasion was significantly lower than in those with deep invasion (13.4 mm (95% CI 11.2-15.7) vs. 18.7 mm (95% CI 15.0-22.3), respectively; p = 0.014). Median CA 125 was significantly higher in patients with deep invasion than in those with superficial invasion (30 IU/ml, interquartile range (IQR) 46.0 vs. 16.9 IU/ml, IQR 13.9, respectively; p = 0.002). The sensitivity, specificity, PPV and NPV for transvaginal ultrasonography were 86.7% (95% CI 59.5-98.3), 94.3% (95% CI 80.8-99.3), 86.7% (95% CI 59.5-98.3) and 94.3% (95% CI 80.8-99.3), respectively. The sensitivity, specificity, PPV and NPV for CA 125 were 40% (95% CI 16.3-67.7), 91.4% (95% CI 76.9-98.2), 66.7% (95% CI 29.9-92.5) and 78% (95% CI 63.4-89.5), respectively. The sensitivity of transvaginal ultrasonography was significantly higher than that of CA 125 (p = 0.008). No differences were found in terms of specificity, PPV or NPV. CONCLUSION: Our results indicate that transvaginal ultrasonography is more sensitive than CA 125 in predicting myometrial invasion in endometrial cancer.     

Lower‐extremity Doppler for Deep Venous Thrombosis—Can Emergency Physicians Be Accurate and Fast?

Clinical diagnosis of lower-extremity (LE) deep venous thrombosis (DVT) requires confirmation by an imaging study before committing the patient to anticoagulation therapy. Studies have shown that demonstrating compressibility of leg veins under ultrasound is accurate for ruling out DVTs when performed by vascular specialists. Although LE Doppler has become the preferred test for diagnosing DVTs, it is not always available 24 hours per day. OBJECTIVES: To evaluate the accuracy and speed with which emergency physicians (EPs) could perform LE color duplex ultrasonography for the detection of DVT. METHODS: Patients presenting to an urban community emergency department (ED) between August 1, 1998, and March 3, 1999, were enrolled into this prospective study. The EPs, who underwent brief and standardized training, scanned patients at high risk for DVT with leg pain, swelling, or both. Physicians performed color duplex ultrasound examinations with compression at the common femoral and popliteal veins. The time until completion of the ED scan was recorded with a standardized method. The vascular laboratory performed a complete duplex ultrasound examination within eight hours. RESULTS: One hundred twelve patients were enrolled in the study, with 34 positive for DVT. The median examination time was 3 minutes 28 seconds (95% CI = 2 min 45 sec to 4 min 2 sec; IQR 3 min 9 sec). Times ranged from 1:02 to 18:20 minutes. The ED results had a high correlation with vascular laboratory studies, giving a kappa of 0.9 and a 98% agreement (95% CI = 95.4% to 100%). CONCLUSION: Emergency physicians can perform LE duplex ultrasound examinations accurately and quickly.     

Diagnostic Performance of Venous Lactate on Arrival at the Emergency Department for Myocardial Infarction

Objectives: To determine the sensitivity of the venous lactate level at presentation for acute myocardial infarction (AMI) in emergency department (ED) patients with chest pain. Methods: A prospective, double‐blind observational study was done in a tertiary care ED. From January to April 2000, all consecutive patients presenting with chest pain were eligible. Lactate level was obtained on arrival and compared with two criterion standards for the diagnosis of AMI: the World Health Organization (WHO) and the Joint European Society of Cardiology/American College of Cardiology Committee (ESC/ACC) classifications. A lactate level greater than 1.50 mmol/L was considered positive. Results: Between January and April 2000, 718 patients were enrolled. By the WHO criteria, 64 patients suffered an AMI, of whom 59 had an elevated lactate level, yielding a sensitivity of 92% (95% CI = 86% to 99%), a specificity of 44% (95% CI = 40% to 48%), and a negative predictive value (NPV) of 98% (95% CI = 97% to 99%). For all patients presenting with more than two hours of chest pain (n=34), the lactate level was elevated. When using the ESC/ACC criteria, 100 patients sustained an AMI, of whom 88 had an elevated lactate level, yielding a sensitivity of 88% (95% CI = 82% to 94%), a specificity of 46% (95% CI = 42% to 50%), and an NPV of 96% (95% CI = 94% to 98%). Conclusions: Venous lactate level at presentation is highly sensitive for the diagnosis of AMI, particularly in patients with more than two hours of chest pain. Given its limitations in specificity and ability to detect creatine kinase‐MB‐negative/troponin‐positive microinfarcts, further research is needed to determine how lactate can complement other cardiac enzymes in risk‐stratifying all acute coronary syndromes.     

D-二聚体在急性主动脉夹层中的诊断价值

目的 探讨血浆D-二聚体水平在急性主动脉夹层(acute aortic dissection,AAD)早期诊断中的价值.方法 选取2006年1月至2009年3月因胸痛就诊于复旦大学中山医院患者共80例,其中40例经动脉三维CT血管成像(CTA)检查确诊为急性主动脉夹层病例作为ADD组,同期以类似症状就诊但最终排除急性主动脉夹层的40例为对照组,所有患者胸痛发生12 h内检测血浆 D-二聚体,比较ADD组与对照组血浆 D-二聚体水平,分析D-二聚体诊断急性主动脉夹层的敏感性、特异性、阳性预测值、阴性预测值,并绘制D-二聚体诊断急性主动脉夹层的受试者工作曲线(receiver operating char-acteristic curve,ROC曲线).所有数据用SPSS 11.5统计软件分析处理,计量资料采用均数±标准差(χ±s)表示,两组间均数比较采用Mann-Whitney检验,以P<0.05为差异具有统计学意义.结果 ADD组血浆在D-二聚体水平明显高于对照组[(5.48±7.95)vs.(0.64±0.75),P<0.01];D-二聚体(>0.5 μg/mL)诊断急性主动脉夹层的敏感性、特异性、阳性预测值和阴性预测值分别为87.5%,62.5%,70%和83.3%,受试者工作曲线下面积为0.848±0.042,95%CI为0.766-0.930.结论 D-二聚体可作为急性主动脉夹层早期诊断有效的筛选指标.     

D-Dimer test in cancer patients with suspected acute pulmonary embolism

BACKGROUND: The safety of a D-dimer (DD) measurement in cancer patients with clinically suspected pulmonary embolism (PE) is unclear. OBJECTIVES: The aim of this study was to assess the accuracy of the DD test in consecutive patients with clinically suspected PE with and without cancer. METHODS: The diagnostic accuracy of DD (Tinaquant D-dimer) was first retrospectively assessed in an unselected group of patients referred for suspected PE (n = 350). Subsequently, the predictive value of the DD was validated in a group of consecutive inpatients and outpatients with clinically suspected PE prospectively enrolled in a management study (n = 519). The results of the DD test in cancer patients were assessed according to the final diagnosis of PE and the 3-month clinical follow-up. RESULTS: In the first study group, DD showed a sensitivity and a negative predictive value (NPV) of 100% and 100% in patients with cancer and 97% and 98% in those without malignancy, respectively. In the validation cohort, the sensitivity and NPV of DD were both 100% (95% CI 82%-100% and 72%-100%, respectively), whereas in patients without malignancy, the corresponding estimates were 93% (95% CI 87%-98%) and 97% (95% CI, 95%-99%), respectively. The specificity of DD was low in patients with (21%) and without cancer (53%). CONCLUSIONS: A negative DD result safely excludes the diagnosis of PE in patients with cancer. Because of the low specificity, when testing 100 patients with suspected PE, a normal DD concentration safely excludes PE in 15 patients with cancer and in 43 patients without cancer.     

Management of patients with suspected deep vein thrombosis in the emergency department: combining use of a clinical diagnosis model with D-dimer testing

The management of patients presenting to hospital Emergency Departments with suspected deep vein thrombosis is problematic since urgent diagnostic imaging is at times unavailable. We evaluated the accuracy of a rapidly available D-dimer test and the potential of combining D-dimer testing with an explicit clinical model to improve the management of patients with suspected deep vein thrombosis. Two hundred and fourteen patients with suspected deep vein thrombosis presenting to the Emergency Departments of two tertiary care institutions were enrolled in this prospective cohort study. Patients were evaluated by an Emergency Physician who determined the pre-test probability for deep vein thrombosis to be either low, moderate, or high using an explicit clinical model. Patients were managed according to their pre-test probability category by specific algorithms that in all cases included venous ultrasound imaging within 24 h and a 90-day follow-up for the development of thromboembolic complications. Patients also underwent fingerstick SimpliRED(R) whole blood agglutination D-dimer testing; however, D-dimer results did not influence subsequent patient management. D-dimer had a sensitivity of 82.5% and a specificity of 84.9% for the diagnosis of deep vein thrombosis. The observed negative predictive value of D-dimer was 96.9% (95% CI, 93.0% to 99.1%) overall, and 100% (95% CI, 96.3% to 100%) in low probability patients, 94.1% (95% CI, 83.8% to 98.8%) in moderate probability patients, and 86.7% (95% CI, 59.4% to 98.3%) in high probability patients. SimpliRED(R) D-dimer has a high negative predictive value and may be useful in excluding the diagnosis in patients at low pre-test probability for deep vein thrombosis.     

Unprovoked recurrent venous thrombosis: prediction by D-dimer and clinical risk factors

Summary.  Background:  The aim of the study was to determine the predictive value of D-dimer measurement for unprovoked recurrent venous thrombosis and the influence of sex, age and type of first event (unprovoked or provoked). Methods:  Prospective cohort study of 272 patients with a first episode of venous thrombosis that was unprovoked or provoked by a non-surgical trigger. Findings:  The cumulative rate of unprovoked recurrence in patients with a positive D-dimer was 20% at 5 years [5.5/100 patient-years, 95% confidence interval (CI) 3.7–7.8] and in patients with a negative D-dimer 17% (4.1/100 patient-years, 95% CI 2.3–6.9). The rates are not different (hazard ratio 1.3, 95% CI 0.7–2.5). After adjustment for clinical risk factors a positive D-dimer result was significantly associated with an increased risk of unprovoked recurrent thrombosis (hazard ratio 2.0, 95% CI 1.01–3.9). The strongest indicator of risk of recurrence was male sex (hazard ratio 3.3 unadjusted and 2.9 after adjustment). The only determinant of D-dimer in a linear regression model was age ( P  <   0.001). Conclusions:  The analysis indicates that clinical risk factors confound the association between D-dimer and risk of recurrence and when adjusted for these confounders a positive D-dimer result is significantly associated with unprovoked recurrence. The clinical utility of D-dimer measurement in individual patients should be interpreted in conjunction with clinical risk factors.     

Emergency Department compression ultrasound to diagnose proximal deep vein thrombosis

Emergency Department (ED) patients with suspected deep vein thrombosis (DVT) require an objective vascular study such as ultrasound (US) to confirm the diagnosis prior to treatment or disposition. A simple compression US test of the common femoral vein and popliteal vein reliably detects proximal DVT in symptomatic patients. Application of compression US in the ED by Emergency Physicians (EPs) has been tested in a single previous study. We evaluated the ability of ED compression US, performed by EPs, to diagnose proximal DVT as compared to duplex US performed in a vascular laboratory. A prospective, observational study was conducted on a convenience sample of patients presenting to an ED with lower extremity symptoms and signs suggestive of DVT. Patients with a history of DVT in the symptomatic extremity were excluded. Final diagnosis of DVT was made by color-flow duplex US performed in a vascular laboratory. ED compression US was performed by one of six EP sonographers. In compression US, DVT was diagnosed by the inability to compress the common femoral vein or popliteal vein. The examination was considered indeterminate if the veins could not be clearly identified or compressibility was equivocal. For statistical analysis, an indeterminate examination was considered positive. In those cases where ED compression US was discordant with duplex US, and not indeterminate, we retrospectively reviewed the US findings. There were 76 patients who completed the study, and 18 patients (24%) were diagnosed with DVT by duplex US, among whom ED compression US was positive in 14, negative in 2, and indeterminate in 2. Among 58 patients diagnosed without DVT by duplex US, there were 4 false-positive ED compression US examinations and 10 indeterminate examinations. In all, ED compression US was indeterminate in 12 patients (15.8%). Compared to duplex US, ED compression US had a sensitivity of 88.9% (95% C.I. 65.3-98.6%) and specificity of 75.9% (62.8-86.1). Negative predictive value was 95.7% (85.2-99.5). Among ED patients with the clinical diagnosis of possible DVT, negative ED compression US greatly reduces the likelihood of DVT, such that discharge and outpatient follow-up can be considered. Because of limited specificity, positive results require confirmation, but may justify immediate treatment pending follow-up testing. Indeterminate results can be expected in a significant number of patients and mandate further testing prior to disposition.     

Lupus anticoagulants and the risk of a first episode of deep venous thrombosis

We have determined lupus anticoagulants, anti-beta2 glycoprotein I (beta2GPI) and antiprothrombin antibodies in the Leiden Thrombophilia Study, a population-based case-control study designed to determine risk factors for deep venous thrombosis (DVT). Lupus anticoagulant (LAC) was measured in 473 patients and 472 control subjects. Four control subjects (0.9%) and 14 patients (3.1%) had a positive LAC, resulting in a 3.6-fold increased risk [odds ratio (OR) 3.6, 95% CI: 1.2-10.9]. Of the total population, 49 were positive for anti-beta2GPI antibodies: 15 controls (3.4%) and 34 patients (7.5%), implying a 2.4-fold increased risk (95% CI: 1.3-4.2). Antiprothrombin antibodies were present in 114 subjects: 48 controls (11.0%) and 66 cases (14.6%) with an OR of 1.4 (95% CI: 1.0-2.1). When LAC was considered in the co-presence of antiprothrombin or anti-beta2GPI antibodies the OR increased to 10.1 (95% CI: 1.3-79.8). A LAC without a positive anti-beta2GPI or antiprothrombin test was not associated with a risk for DVT (OR 1.3, 95% CI: 0.3-6.0). This study demonstrates that the presence of LAC, anti-beta2GPI antibodies and antiprothrombin antibodies are risk factors for DVT in a general population. The strongest association holds for the combination LAC and the presence of anti-beta2GPI or antiprothrombin antibodies.     

A comparative study of the risk of malignancy index and the ovarian crescent sign for the diagnosis of invasive ovarian cancer.

OBJECTIVE: To compare the value of the risk of malignancy index (RMI) and the ovarian crescent sign (OCS) in the diagnosis of ovarian malignancy. METHODS: This was a prospective observational study of women with ultrasonographic diagnosis of an ovarian cyst. The RMI was calculated in all cases using a previously published formula (RMI = U (ultrasound score) x M (menopausal status) x serum CA125 (kU/L)). A value > 200 was considered to be diagnostic of ovarian cancer. The OCS was defined as a rim of visible healthy ovarian tissue in the ipsilateral ovary. Its absence was taken as being diagnostic of invasive cancer. RESULTS: A total of 106 consecutive women were included in the study, of whom 92 (86.8%) had a benign ovarian tumor, five (4.7%) had borderline lesions and nine (8.5%) had an invasive ovarian cancer. The absence of an OCS diagnosed invasive ovarian cancer with a sensitivity of 100% (95% CI, 70-100%), specificity of 93% (95% CI, 86-96%), positive predictive value (PPV) of 56%, negative predictive value (NPV) of 100% and positive likelihood ratio (LR+) of 13.86 (95% CI, 6.79-28.29). This compared favorably with a sensitivity of 89% (95% CI, 57-98%), specificity of 92% (95% CI, 85-96%), PPV of 50%, NPV of 99% and LR+ of 10.78 (95% CI, 5.34-21.77), which were achieved using RMI > 200 (P < 0.01). CONCLUSIONS: The RMI and the OCS are useful tests for discriminating between invasive and non-invasive ovarian tumors. The application of these tests in a sequential manner might improve the overall accuracy of ovarian cancer diagnosis.     

Comparison of the age-adjusted and clinical probability-adjusted D-dimer to exclude pulmonary embolism in the ED

Background

Diagnosing pulmonary embolism (PE) in the emergency department (ED) can be challenging because its signs and symptoms are non-specific.

S100A8/A9: A Potential New Diagnostic Aid for Acute Appendicitis

Objectives: Diagnosing acute appendicitis is a daunting clinical challenge, as there is no single test that reliably distinguishes acute appendicitis from other etiologies of acute abdominal pain. In this study, the authors examined whether circulating levels of S100A8/A9 could be useful as a marker to aid in the diagnosis of acute appendicitis. Methods: Plasma samples from emergency department (ED) patients with acute abdominal pain (n = 181) were tested using an immunoassay for S100A8/A9. Results: The sensitivity and specificity for S100A8/A9 in diagnosing acute appendicitis were estimated to be 93% (95% confidence interval [CI] = 81% to 97%) and 54% (95% CI = 45% to 62%), respectively. Negative predictive value (NPV) was 96% (95% CI = 89% to 99%), and positive predictive value (PPV) was 37% (95% CI = 28% to 47%). Performance characteristics of elevated white blood cell (WBC) count were also estimated: sensitivity 63% (95% CI = 47% to 76%), specificity 67% (95% CI = 59% to 75%), NPV 86% (95% CI = 78% to 91%), and PPV 36% (95% CI = 26% to 47%). Conclusions: This is the first report exploring the relationship between circulating S100A8/A9 and acute appendicitis and establishes proof of concept for this biomarker as a diagnostic test for acute appendicitis. Further studies are indicated to optimize the use of this biomarker, in conjunction with other established approaches. ACADEMIC EMERGENCY MEDICINE 2010; 17:333–336 © 2010 by the Society for Academic Emergency Medicine     

血浆D-二聚体对疑似肺栓塞患者诊断价值的研究

目的：探讨血浆 D-二聚体对对疑似肺栓塞患者的诊断价值。方法采用自动化免疫比浊法测定患者血浆D-二聚体水平。统计分析血浆D-二聚体诊断肺栓塞的敏感性、特异性、阴性及阳性预测值,并绘制ROC曲线以评价其诊断价值并对D-二聚体阴性排除肺栓塞价值进行分析。结果在317例疑似肺栓塞患者中D-二聚体＜500μg/L的患者73例,其中6例被诊断为肺栓塞。D-二聚体对肺栓塞的诊断的敏感性为95.86%（95%CI：91.27%～98.08%）,特异性为38.95%（95%CI：31.98%～41.41%）,阴性预测值为91.78%（95%CI：83.21%～96.18%）,阳性预测值为56.97%（95%CI：50.69%～63.02%）,诊断准确性为64.98%（95%CI：59.58%～70.03%）。ROC曲线下面积为0.674（95%CI：0.615～0.733）。结论 D-二聚体对肺栓塞的诊断具有较高的敏感性,阴性排除肺栓塞的准确性较高,但仍可受患者年龄、测试方法等的影响。