Quantitative D-dimer Research Articles

Simple and safe exclusion of pulmonary embolism in outpatients using quantitative D-dimer and Wells’ simplified decision rule

A safe and effective management strategy is pivotal in excluding pulmonary embolism (PE). The combination of Wells' simplified dichotomous clinical decision rule and D-dimer test is non-invasive and could be highly efficient, though its safety has not been widely studied. We evaluated safety and efficiency of this combination in excluding PE. Wells clinical decision rule was performed in 941 consecutive patients with suspected PE and, if patients had a score <or=4.0 points, a VIDAS D-dimer test followed. Patients with a normal D-dimer concentration had no further tests, PE was considered excluded, and patients did not receive anticoagulant treatment. Patients, in whom PE was excluded, were followed up for three months. Four hundred fifty patients (51.2%) had a clinical decision score =4.0 points and a normal D-dimer concentration. In 45 of these patients, during the initial diagnostic period additional objective testing, although not indicated, was performed, and PE was established in two patients. During three months of follow up no venous thromboembolic events (VTE) occurred. Therefore, the overall VTE failure rate was two of 450 (0.4% [95%CI 0-1.1]); the overall prevalence of PE was 12.3%. The diagnostic protocol could be completed and allowed a decision to be made in 90% of the study patients. This study has prospectively established the safety of a combination of a dichotomized clinical decision rule and D-dimer test in ruling out PE. The strategy proved highly efficient, since more than 50% of patients could be managed without the need for more invasive and expensive tests.

PO-19 Are quantitative D-dimer levels only useful in the diagnosis of venous thrombosis? Predictive role of quantitative D-dimer levels in patients with venous thrombosis

PO-19 Are quantitative D-dimer levels only useful in the diagnosis of venous thrombosis? Predictive role of quantitative D-dimer levels in patients with venous thrombosis

Clinically suspected acute recurrent pulmonary embolism: A diagnostic challenge

It is unknown whether strategies validated for diagnosing pulmonary embolism (PE) are valid in patients with a history of PE. It was the objective of this study to investigate whether a diagnostic algorithm consisting of sequential application of a clinical decision rule (CDR), a quantitative D-dimer test and computed tomography (CT) safely ruled out a clinical suspicion of acute recurrent PE. Data were obtained from a diagnostic outcome study of patients suspected of PE. Acute recurrent PE was ruled out by an unlikely probability of PE (CDR score </= 4 points) combined with a normal D-dimer test (</= 500 ng/ml) or by a normal CT in all other patients. The primary outcome was the incidence of acute recurrent venous thromboembolism during three months of follow-up in patients with normal tests and not treated with anticoagulants. Of 3,306 patients suspected of acute PE, 259 patients (7.8%) had a history of PE of whom 234 were not treated with anticoagulants. The probability of PE was unlikely in 82 of 234 patients (35%), and 42 had a normal D-dimer test (18%), excluding recurrent PE. None of these patients had a thrombotic event during follow-up (0%, 95%CI: 0-6.9). A CT was indicated in all other patients (192) and ruled out recurrent PE in 127 patients (54%). Only one patient with a negative CT had a fatal recurrent PE during follow-up (0.8%; 95%CI: 0.02-4.3). In conclusion, this prospective study demonstrates the safety of ruling out a clinical suspicion of acute recurrent PE by a simple diagnostic algorithm in patients with a history of PE.

Performance evaluation of a new rapid quantitative assay system for measurement of D-dimer in plasma and whole blood: PATHFAST™ D-dimer

D-dimer is an indicator for in vivo fibrin formation, reflecting the formation of fibrin crosslinked by factor XIIIa. D-dimer assays are frequently used in emergency situations, such as diagnosis of venous thrombosis and pulmonary embolism, or disseminated intravascular coagulation. In these conditions, short sample turnaround times are essential. The PATHFAST D-dimer assay allows rapid quantitative measurement of D-dimer in plasma and whole blood. The study shows an excellent correlation between whole blood and plasma measurement of D-dimer both in the high range, as well as in the normal range. Intra-assay and inter-assay coefficients of variation (CV) were below 10%. The upper limit of normal (ULN = mean value measured in 100 samples from healthy blood donors + 2 × S.D.) was approximately 1 μg/ml FEU, using the assay-specific calibration. The maximal value measured in 20 replicates of calibrator 1 containing no D-dimer antigen was 0.00052 μg/ml FEU, and this 10-fold lower than the declared detection limit of 0.005 μg/ml FEU. In conclusion, the PATHFAST D-dimer assay is the first automated fully quantitative D-dimer assay, which can use plasma and whole blood as sample materials in parallel.

Elevated D-Dimer Level Is a Predictor of Poor Survival Even in Patients without Venous Thromboembolism (VTE).

Use of D-dimer levels along with clinical probability scores in the diagnosis of venous thrombosis is well established. Recently it has been shown that high quantitative D-dimer levels at presentation are predictor for poor survival and underlying malignancy in patients with VTE. Do quantitative D-dimer levels in patients without VTE have a similar predictive role?Materials and MethodsThis study included 2263 (F: 1518; M: 745) consecutive patient episodes from the prospectively maintained database of patients without venous thrombosis at a University Teaching Hospital, between February 2001 and December 2005. All patients with suspected venous thrombosis underwent a Doppler ultrasound examination to rule out venous thrombosis. D-dimer assays were done using Bio-Merieux kit containing mouse monoclonal antibody. The database was regularly updated (6 monthly) using hospital information systems, questionnaires and clinical review.Statistical analysis was carried out using SPSS 13.0 for Windows and GraphPad InStat ® Version 3.06 for Windows software's. Overall survival (OS) was estimated by the Kaplan-Meier method. Cox regression analysis by forward Likelihood Ratio was subsequently used to explore the independent effect of variables that showed a significant influence on OS.ResultsMedian age at diagnosis was 69 yrs (range: 18–105 yrs). Median D-dimer level was 1000ug FEU/ml (range: 300–35500ug FEU/ml). 1165 patients (51.7%) had a D-dimer level of >1000ug FEU/ml and 40 (2%) had a D-dimer level of >8000ug FEU/ml at presentation. 1472 patients (65.4%) were aged above 60 years. Median follow up was 22 months (range: 0–65 months). D-dimer level >1000ug FEU/ml, >4000ug FEU/ml and >8000ug FEU/ml were associated with decreased overall survival (Log rank test: p value: 0.002, < 0.001 and <0.001 respectively). Age>60 yr is also associated with decreased overall survival (Log rank test: p value: <0.001). D-dimer >8000ug FEU/ml and age>60yr were an independent poor prognostic factor for overall survival on Cox regression analysis (p value: <0.001). 27.5% of patients with a D-dimer level >8000ug FEU/ml had cancer (Fisher's exact test; p value: 0.003). 17% of patients with a D-dimer level >4000ug FEU/ml had cancer (Fisher's exact test; p value: 0.04). 12.4% of patients with a D-dimer level >1000ug FEU/ml had cancer (Fisher's exact test; p value: 0.02).ConclusionsThis study show elevated D-dimer levels at presentation in patients without venous thrombosis is a marker of poor survival and a predictor for underlying malignancy. We have previously shown that D-dimer >8000ug FEU/ml is a predictor for poor survival and underlying malignancy in patients with proven venous thrombosis. This suggests heightened fibrinolytic activity in the absence or presence of established venous thrombosis is associated with poor prognosis. Further studies are warranted to establish in different medical conditions the presence or absence of increased fibrinolysis and impact on clinical outcome.

A Predictive Model To Identify Patients with Venous Thromboembolism (VTE) at Minimal Risk of Malignancy.

Association between VTE and cancer has been recognised for over a century. The incidence of occult or overt malignancy in patients with thrombosis is 7–26%. VTE has been shown to impart poor prognosis in patients with cancer and cancer also adversely impacts on the survival of patients with VTE. It is desirable to identify patients with thrombosis at increased risk of malignancy or those with minimal risk, thus avoiding unnecessary investigations. We propose here a predictive model using age and quantitative D-dimer level at presentation along with site of thrombosis.Materials and MethodsThis study included 696 (M: 358; F: 338) consecutive patients from the prospectively maintained database of patients with venous thrombosis at a University Teaching Hospital, between February 2001 and December 2005. All patients underwent a Doppler ultrasound examination to confirm the diagnosis and determine the extent of venous thrombosis. At presentation, D-dimer assays were done using Bio-Merieux kit containing mouse monoclonal antibody. The database was regularly updated (6 monthly) using hospital information systems, questionnaires and clinical review Thrombosis recurrence was always confirmed by Doppler ultrasound examination. All Patients with thrombosis received standard treatment with low molecular weight heparin and warfarin. Statistical analysis was carried out using SPSS 13.0 for Windows software. A logistic multivariate regression model was fitted using complete data records from 621 patients with an indicator variable for a subsequent cancer as the response and age, the natural logarithm of the quantitative D-dimer level and the site of the thrombosis as explanantory variables. The fitted model was validated using an additional set of independent data.ResultsThe model correctly identified the VTE patients without malignancy in 473 out of 480 cases (98.5% accuracy). But the model was ineffective in identifying VTE patients with malignancy (13 out of 141; 9% accuracy). The area under the receiver operating characteristic (ROC) curve was 0.72, indicating that the test developed for predicting cancer for the model data was reasonably good. Our model shows that below a predicted probability of 0.10 less than 5% of the patients actually developed cancer (9/190) whereas for a predicted probability of 0.19 less than 10% of patients actually developed cancer (27/276). In the validation dataset of 93 patients with VTE, the model correctly identified the number of patients without malignancy in 72 out of 73 cases (98.6% accuracy). One-sample binomial tests revealed that there was no significant difference in the number VTE patients with cancer between the model and the validation dataset for the predicted probabilities of 0.10 and 0.19 (p-values of 0.650 and 0.246 respectively).ConclusionsThis suggests that our model is useful for identifying patients at minimal risk of developing cancer with VTE. This predictive model has been validated by an independent dataset demonstrating reproducibility. This model will enable a focused and a cost-effective strategy of screening for a malignancy in patients with VTE.

Different Accuracies of Rapid Enzyme-Linked Immunosorbent, Turbidimetric, and Agglutination D-Dimer Assays for Thrombosis Exclusion: Impact on Diagnostic Work-Ups of Outpatients with Suspected Deep Vein Thrombosis and Pulmonary Embolism

The requirement for a safe diagnostic strategy should be based on an overall posttest incidence of venous thromboembolism (VTE) of less than 1%, with a negative predictive value of more than 99 to 100% during 3-month follow-up. Compression ultrasonography (CUS) and spiral computed tomography (CT) currently are the methods of choice to confirm or rule out deep venous thrombosis (DVT) and pulmonary embolism (PE), respectively. CUS has a negative predictive value (NPV) of 97 to 98%, indicating the need to improve the diagnostic work-up of patients with suspected DVT by clinical score assessment and D-dimer testing. Spiral CT as a stand-alone method detects all clinically relevant PEs and a large number of alternative diagnoses. It rules out PE with a NPV of 98 to 99%. Spiral CT is expensive, emphasizing the need to improve the diagnostic work-up of patients with suspected PE by the use of clinical score assessment and D-dimer testing. Clinical score assessment for DVT and PE has not safely ruled out VTE in multicenter studies and in routine daily practices. Modification of the Wells clinical score assessment for DVT by elimination of the "minus 2 points" for alternative diagnosis will improve the reproducibility of the clinical score assessment. The combination of a first negative CUS and a negative SimpliRed or an enzyme-linked immunosorbent assay (ELISA) VIDAS D-dimer of < 1,000 ng/mL safely exclude DVT (NPV > 99%) irrespective of clinical score assessment and without the need to repeat CUS in approximately 60 to 70% of patients. The rapid quantitative and qualitative agglutination D-dimer assays for the exclusion of VTE are not sensitive enough as stand-alone tests and should be used in combination with clinical score assessment. A normal rapid ELISA VIDAS D-dimer test as a stand-alone test safely excludes DVT and PE, with a NPV of 99 to 100%, irrespective of clinical score, without the need of CUS or spiral CT. The combined strategy of a rapid ELISA VIDAS D-dimer followed by objective testing with CUS for DVT and by spiral CT for PE will reduce the need for noninvasive imaging techniques by 40 to 50%.

ID: 295 Performance of a new rapid quantitative D-dimer assay (HemosIL D-dimer Plus) in the diagnosis of pulmonary embolism. Comparison with other quantitative assays. Preliminary results.

ID: 295 Performance of a new rapid quantitative D-dimer assay (HemosIL D-dimer Plus) in the diagnosis of pulmonary embolism. Comparison with other quantitative assays. Preliminary results.

ID: 118 The repeatability of quantitative D-Dimer assays in clinical laboratories.

ID: 118 The repeatability of quantitative D-Dimer assays in clinical laboratories.

High D‐dimer levels at presentation in patients with venous thromboembolism is a marker of adverse clinical outcomes

Qualitative D-dimer results, together with clinical probability scores, are well established in the diagnosis of venous thromboembolism (VTE). The predictive value of quantitative D-dimer levels for various clinical outcomes in VTE patients is not fully understood. D-dimer levels obtained at presentation were analysed in 699 (360 men; 339 women) VTE patients for survival and occurrence of malignancy. Patients were followed for a median of 23 months. 17.2% patients had a D-dimer level >8000 ng FEU/mlat presentation, which was associated with decreased overall survival (OS) (P < 0.001) and event-free survival (EFS) (P < 0.001). 25.4% patients had malignancy and 4% subsequently developed malignancy following VTE. 29.9% of patients with VTE and malignancy had a D-dimer level >8 mg/l when compared with 13.4% of patients with VTE without malignancy (P < 0.001). 50% of patients who developed subsequent malignancy following VTE had a presentation D-dimer >8000 ng FEU/mlas compared with 13.3% of patients with VTE with out malignancy (P = 0.009). In conclusion, D-dimer >8000 ng FEU/ml at presentation in patients with VTE is a marker of poor OS, EFS and underlying malignancy. Consideration of screening for malignancy is recommended in patients with VTE with a presentation D-dimer >8000 ng FEU/ml and age >60 years.

Value of Quantitative D‐dimer Assays in Identifying Pulmonary Embolism: Implications from a Sequential Decision Model

To examine the cost-effectiveness of a quantitative D-dimer assay for the evaluation of patients with suspected pulmonary embolism (PE) in an urban emergency department (ED). The authors analyzed different diagnostic strategies over pretest risk categories on the basis of Wells criteria by using the performance profile of the ELISA D-dimer assay (over five cutoff values) and imaging strategies used in the ED for PE: compression ultrasound (CUS), ventilation-perfusion (VQ) scan (over three cutoff values), CUS with VQ (over three cutoff values), computed tomography (CT) angiogram (CTA) with pulmonary portion (CTP) and lower-extremity venous portion, and CUS with CTP. Data used in the analysis were based on literature review. Incremental costs and quality-adjusted-life-years were the outcomes measured. Computed tomography angiogram with pulmonary portion and lower-extremity venous portion without D-dimer was the preferred strategy. CUS-VQ scanning always was dominated by CT-based strategies. When CTA was infeasible, the dominant strategy was D-dimer with CUS-VQ in moderate- and high-Wells patients and was D-dimer with CUS for low-Wells patients. When CTP specificity falls below 80%, or if its overall performance is markedly degraded, preferred strategies include D-dimer testing. Sensitivity analyses suggest that pessimistic assessments of CTP accuracy alter the results only at extremes of parameter settings. In patients in whom PE is suspected, when CTA is available, even the most sensitive quantitative D-dimer assay is not likely to be cost-effective. When CTA is not available or if its performance is markedly degraded, use of the D-dimer assay has value in combination with CUS and a pulmonary imaging study. These conclusions may not hold for the larger domain of patients presenting to the ED with chest pain or shortness of breath in whom PE is one of many competing diagnoses.

Value of Quantitative D-dimer Assays in Identifying Pulmonary Embolism: Implications from a Sequential Decision Model

Value of Quantitative D-dimer Assays in Identifying Pulmonary Embolism: Implications from a Sequential Decision Model

A model for the harmonisation of test results of different quantitative D-dimer methods

The numerical test results of different D-dimer assays vary widely. Because of the complexity of the analyte of target as well as the variability in specificity of different D-dimer assays, only harmonisation of the test results seems to be feasible. The use of a single conversion factor does not take into account for several methods the lack of commutability between test results and consensus values at different D-dimer levels. This is probably related to the mutually different response of methods to high and low levels. We therefore designed a harmonisation model based on the transformation of a method-specific regression line to a reference regression line. We used the data for the measurement of a set of plasma samples with different D-dimer levels by 353 different laboratories using 7 of the most frequently used quantitative D-dimer methods. For each method we calculated the method-specific consensus value for each sample. The overall median value was also estimated. Per method linear regression was applied throughout the method-specific consensus values using the amount of patient pooled plasma added to the different plasma samples as the independent variable. The line through the overall median values of all 7 methods was used as the reference line. Harmonisation between the methods was obtained by transformation of the method-specific regression line to the reference line. This harmonisation resulted in a reduction of the variability between the method-specific consensus values from about 75% to about 5.5%. Clinical validation of this concept had shown significant improvement of the test result comparability. We conclude that this model is a feasible approach in the harmonisation of D-dimer methods. If the harmonisation procedure is included in the calibration procedure by the manufacturers, customers will automatically obtain harmonised test results.

Role of a Quantitative d-Dimer Assay in Determining the Need for CT Angiography of Acute Pulmonary Embolism

Role of a Quantitative d-Dimer Assay in Determining the Need for CT Angiography of Acute Pulmonary Embolism

D-dimer is not useful for the diagnosis of isolated superficial venous thrombosis

D-dimer is not useful for the diagnosis of isolated superficial venous thrombosis

The Harmonization of Quantitative Test Results of Different D-Dimer Methods

Nowadays D-dimer testing is frequently applied in the diagnosis of venous thromboembolism. However, the test results of different quantitative D-dimer tests can differ significantly. The background of this variability, which is mainly caused by the variety of fibrin degradation products in plasma, the specificity of D-dimer assays, and the calibrators used in the test, is summarized here. Because D-dimer is not a single entity in plasma but a mixture of heterogeneous fibrin degradation products, method standardization is in principle impossible. Efforts undertaken in the past to standardize D-dimer methods are summarized. All these projects failed and it was concluded that only harmonization of D-dimer test results seems to be feasible. The results of a large field study on which a new approach to the harmonization of quantitative D-dimer methods will be based is summarized in this article. This approach seems to be an adequate solution for overcoming the practical problem of variation of test outcome in different D-dimer assays.

Screening for Deep Vein Thrombosis and Pulmonary Embolism in Outpatients with Suspected DVT or PE by the Sequential Use of Clinical Score: A Sensitive Quantitative D-Dimer Test and Noninvasive Diagnostic Tools

The requirement for a safe diagnostic strategy should be based on an overall posttest incidence of venous thromboembolism (VTE) of less than 1% during 3-month follow-up. The negative predictive value (NPV) during 3 months of follow-up is 98.1 to 99% after a normal venogram, 97 to 98% after a normal compression ultrasonography (CUS), and > 99% after serial CUS testing. Serial CUS testing is safe but 100 CUS must be repeated to find one or two CUS positive for deep vein thrombosis (DVT), which is not cost-effective and indicates the need to improve the diagnostic workup of DVT by the use of clinical score assessment and D-dimer testing. The NPV varies from 97.6 to 99.4% for low clinical score followed by a negative SimpiRED test, indicating the need for a first CUS. The NPV is 98.4 to 99.3% for a normal rapid enzyme-linked immunosorbent assay (ELISA) VIDAS D-dimer test result (< 500 ng/mL) irrespective of clinical score. The NPV is more than 99% for a negative CUS followed by either a negative SimpiRED test or an ELISA VIDAS test result of < 1000 ng/mL without the need to repeat a second CUS within 1 week. The sequential use of a sensitive, rapid ELISA D-dimer and clinical score assessment will safely reduce the need for CUS testing by 40 to 60%. Large prospective outcome studies demonstrate that with one negative examination with complete duplex color ultrasonography (CCUS) of the proximal and distal veins of the affected leg with suspected DVT, it is safe to withhold anticoagulant treatment, with a negative predictive value of 99.5%. This may indicates that CCUS is equal to serial CUS or the combined use of clinical score, D-dimer testing, and CUS. Pulmonary angiography is the gold standard for segmental pulmonary embolism (PE) but not for subsegmental PE. A normal perfusion lung scan and a normal rapid ELISA VIDAS D-dimer test safely excludes PE. Helical spiral computed tomography (CT) detects all clinically relevant PE and a large number of alternative diagnoses in symptomatic patients with suspected PE and can replace both the ventilation perfusion scan and pulmonary angiography to safely rule in PE and to rule out PE with an NPV of > 99%. The combination of clinical assessment, a rapid ELISA VIDAS D-dimer, followed by CUS will reduce the need for helical spiral CT by 40 to 50%.

Validation, Calibration, and Specificity of Quantitative D-Dimer Assays

Assays for D-dimer antigen are based on monoclonal antibodies reactive with epitopes found on fibrin fragment D-dimer but not on fibrinogen fragment D, other fibrinogen degradation products, or native fibrinogen. The antibodies react with conformational epitopes generated by factor XIII-induced linkage of the C-terminal appendages of the fibrin gamma-chains of adjacent D-domains within a fibrin polymer. For some monoclonal antibodies, degradation of the cross-linked fibrin compound by plasmin is an additional requirement for the generation of the epitope. In clinical plasma samples, D-dimer antigen assays detect an array of fibrin compounds of different molecular weights, including fibrin fragment D-dimer as well as higher-molecular-weight fibrin degradation products and fibrin X-oligomers. Most D-dimer antigen represents cross-linked soluble fibrin present in circulation rather than degradation products from particulate clots. Due to differences in epitope reactivity, harmonization of D-dimer antigen assays can only be achieved with standard preparations containing a similar variety of cross-linked fibrin compounds. Assay technologies include manual latex agglutination assays, automated latex-enhanced light-scattering immunoassays, enzyme-linked immunoassays, and others.

High D-Dimer Levels at Presentation in Patients with Venous Thrombosis Is a Marker of Poor Overall and Event Free Survival.

The role of D-dimer estimation along with clinical probability scoring is well established in the diagnosis of deep venous thrombosis. The issue of predictive value of quantitative D-dimer analysis to various clinical outcomes are being addressed. We have studied here the effect of quantitative D-dimer level at presentation in patients with deep venous thrombosis on overall survival (OS), event free survival (EFS), extent of thrombosis and occurrence of malignancy.MethodsThis study included 608 (F: 305; M: 303) consecutive patients from the prospectively maintained database of patients with venous thrombosis at a University Teaching Hospital, between February 2001 and May 2005. All patients underwent an Doppler ultrasound examination to confirm the diagnosis and determine the extent of venous thrombosis. The database was regularly updated (6 monthly) using hospital information systems, questionnaires and clinical review. D-dimer assays were done using Bio-Merieux kit containing mouse monoclonal antibody. Thrombosis recurrence was always confirmed by Doppler ultrasound examination. All Patients with thrombosis received standard treatment with low molecular weight heparin and Warfarin. OS and EFS were estimated by the Kaplan-Meier method. For the purpose of EFS analyses, death, thrombosis recurrence, pulmonary embolism and malignancy occurrence were all considered as events. Cox regression analysis was subsequently used to explore the independent effect of variables that showed a significant influence on OS or EFS by univariate analysis. P values < 0.05 were considered significant.Results:Median age at diagnosis was 64yrs (Range: 16–96 yrs) and median follow up was 22 months (Range: 0–51 months). Median D-dimer level at presentation was 2.3 mg/ml (Range: 0.1–46.3 mg/ml). 341 (58.3%) patients had above knee thrombosis, 244 (41.7%) patients had below knee venous thrombosis and 14 (2.3%) patients had upper limb thrombosis. 132 (22.2%) patients either had or developed malignancy during the study period. Recurrence of thrombosis was observed in 28 patients (4.6%). Both univariate and multivariate analysis confirmed the independent poor prognostic impact of age > 60 yrs, D-dimer > 8mg/ml and above knee thrombosis on OS (P = 0.001, 0.007 & 0.045, respectively) and EFS (P = 0.032, 0.008 & 0.003, respectively). D-dimer > 8mg/ml was also associated with occurrence of malignancy (P value: <0.001) and above knee venous thrombosis (P < 0.001). Neither elevated D-dimer nor above knee thrombosis were predictive of recurrence, whereas age < 60 yrs at diagnosis was associated with increased risk of recurrence of thrombosis (P = 0.006).Conclusions:Elevated D-dimer at presentation was associated with decreased event free survival and overall survival in patients with venous thrombosis. High D-dimer at presentation was a marker for underlying malignancy in patients with thrombosis and was also a predictor of extensive thrombosis. Further studies are warranted to ascertain, whether alternative anticoagulation regimens like prolonged anticoagulation or more intensive anticoagulation negates the adverse impact of high D-dimer at presentation in patients with venous thrombosis.

Systematic Review and Meta-Analysis of Strategies for the Diagnosis of Suspected Pulmonary Embolism

Objective To assess the likelihood ratios of diagnostic strategies for pulmonary embolism and to determine their clinical application according to pretest probability. Data sources Medline, Embase, and Pascal Biomed and manual search for articles published from January 1990 to September 2003. Study selection Studies that evaluated diagnostic tests for confirmation or exclusion of pulmonary embolism. Data extracted Positive likelihood ratios for strategies that confirmed a diagnosis of pulmonary embolism and negative likelihood ratios for diagnostic strategies that excluded a diagnosis of pulmonary embolism. Data synthesis 48 of 1012 articles were included. Positive likelihood ratios for diagnostic tests were: high probability ventilation perfusion lung scan 18.3 (95% confidence interval 10.3 to 32. 5) , spiral computed tomography 24. 1 (12. 4 to 46. 7) , and ultrasonography of leg veins 16. 2 (5. 6 to 46. 7). In patients with a moderate or high pretest probability, these findings are associated with a greater than 85% post-test probability of pulmonary embolism. Negative likelihood ratios were: normal or near normal appearance on lung scan 0. 05 (0. 03 to 0. 10) , a negative result on spiral computed tomography along with a negative result on ultrasonography 0. 04 (0. 03 to 0. 06) , and a D-dimer concentration 500 μg/L measured by quantitative enzyme linked immunosorbent assay 0.08 (0.04 to 0. 18) . In patients with a low or moderate pretest probability, these findings were associated with a post-test probability of pulmonary embolism below 5% . Spiral computed tomography alone, a low probability ventilation perfusion lung scan, magnetic resonance angiography, a quantitative latex D-dimer test , and haemagglutination D-dimers had higher negative likelihood ratios and can therefore only exclude pulmonary embolism in patients with a low pretest probability. Conclusions The accuracy of tests for suspected pulmonary embolism varies greatly, but it is possible to estimate the range of pretest probabilities over which each test or strategy can confirm or rule out pulmonary embolism.