A multicenter evaluation of a new quantitative highly sensitive D-dimer assay for exclusion of venous thromboembolism

D-dimer testing is widely applied for exclusion of deep-vein thrombosis (DVT) and pulmonary embolism (PE). We report on a multicenter performance evaluation of a new particle-enhanced immunoassay, Innovancetrade mark D-Dimer. Innovance D-Dimer assay was performed in 1,543 frozen samples from outpatients suspected of DVT and/or PE enrolled in three management studies as well as in a routine clinical practice. Samples were assayed on BCS((R))/BCS((R)) XP, BCT((R)) as well as Sysmex((R)) CA-7000, CA-1500 and CA-560 analyzers (cut-off on all analyzers: 0.5 mg/l). Stratus((R)) CS D-Dimer and Vidas((R)) D-Dimer Exclusion were used for comparison. The precision study indicated total coefficients of variation ranging from 2.1% to 8.4% depending on the analyzer and on the sample. Sensitivity and negative predictive values were above 99% and their lower 95% confidence interval were equal or above 97.4% and 98.6%, respectively. Specificity ranged from 38.2% to 40.4% and the respective lower 95% confidence intervals from 35.5% to 37.7%. Area under the curve was 0.90 for all assay systems except for Innovance D-Dimer with BCT (0.89). Two samples from patients with distal DVT tested negative with all assay systems. One patient with high pre-test clinical probability and proximal DVT tested negative with Vidas D-Dimer Exclusion. Our data indicate that the performances of Innovance D-Dimer, regardless of the analyzer, are similar to the reference methods, and that this assay can be used for the exclusion of venous thromboembolic disease.     

Multicenter evaluation of a new quantitative highly sensitive D-dimer assay, the Hemosil® D-dimer HS 500, in patients with clinically suspected venous thromboembolism

Introduction

D-dimer testing is widely used in conjunction with clinical pretest probability (PTP) for venous thromboembolism (VTE) exclusion. We report on a multicenter evaluation of a new, automated, latex enhanced turbidimetric immunoassay [HemosIL® D-Dimer HS 500, Instrumentation Laboratory (IL)].

Materials and Methods

747 consecutive outpatients with suspected proximal deep vein thrombosis (DVT, n = 401) or pulmonary embolism (PE, n = 346) were evaluated at four university hospitals in a management study with a 3 month follow-up. Samples were tested at each center using the new D-dimer assay on an automated coagulation analyzer [ACL TOP (IL)], with clinical cut-off for VTE at 500 ng/mL (FEU).

Results

The sensitivity and negative predictive value (NPV) were 100% for all PTP subgroups (no false negative results); for both sensitivity and NPV the lower limit of the 95% CI in patients with moderate/low PTP was higher than 95%. The overall specificity was 45.1% (95%CI: 41.1-49.3%). Higher specificity value was recorded in the low PTP subgroup [49.2% (95%CI: 41.7-56.7)]. No significant differences were found between patients suspected of having DVT or PE; sensitivity and NPV were 100%. The reproducibility of the assay was good, being the total CVs% less than 10% for D-dimer concentration near the clinical cut-off.

Conclusions

The new, highly sensitive D-dimer assay proved to be accurate when used for VTE diagnostic work-up in outpatients. Based on 100% sensitivity and NPV and lower limit of the 95% CI higher than 95%, the assay can be used as a stand-alone test in patients with non high PTP.     

Risk of venous thromboembolism recurrence: high negative predictive value of D-dimer performed after oral anticoagulation is stopped

In some patients with previous venous thromboembolism (VTE) D-dimer levels (D-Dimer) tend to increase after oral anticoagulant therapy (OAT) is stopped. The aim of our study was to evaluate the predictive value of D-Dimer for the risk of VTE recurrence after OAT withdrawal. After a first episode of deep vein thrombosis (DVT) of the lower limbs and/or pulmonary embolism (PE), 396 patients (median age 67 years, 198 males) were followed from the day of OAT discontinuation for 21 months. D-dimer was measured on the day of OAT withdrawal (T1), 3-4 weeks (T2) and 3 months (+/- 10 days, T3) thereafter. The main outcome events of the study were: objectively documented recurrent DVT and/or PE. D-dimer was found to be increased in 15.5%, 40.3% and 46.2% of the patients at T1, T2 and T3, respectively. In 199 (50.2%) patients, D-dimer levels were elevated in at least one measurement. During a follow-up of 628.4 years, 40 recurrences were recorded (10.1% of patients; 6.4% patient-years of follow-up). D-dimer was increased in at least one measurement in 28 of these cases, but remained normal in 11 subjects (three of whom had recurrent events triggered by circumstantial factors, three with malignancy-associated factors) (in one subject D-dimer was not measured). The negative predictive value (NPV) of D-dimer was 95.6% (95% CI 91.6-98.1) at T3 and was even higher (96.7%; 95% CI 92.9-98.8) after exclusion of the six recurrences due to circumstantial factors. Only five idiopathic recurrences occurred in the 186 patients with consistently normal D-dimer. In conclusion, D-dimer has a high NPV for VTE recurrence when performed after OAT discontinuation.     

Performances of the fibrin monomer test for the exclusion of pulmonary embolism in symptomatic outpatients

Many studies have shown that D-dimer determinations can be used for the exclusion of venous thromboembolism in symptomatic outpatients, depending however on the method of D-dimer measurement. Another related assay, the Fibrin Monomer test which measures soluble fibrin levels in plasma by ELISA, is now available. We have evaluated the performances of this assay for the exclusion of pulmonary embolism (PE) in 426 consecutive outpatients presenting at the emergency ward of our institution. Diagnosis of PE was made by D-dimer measurement, compression ultrasonography, lung scintigraphy, venography and pulmonary angiography. With a cut-off of 3 microg/ml. the sensitivity and the negative predictive value were both 100% (95% CI: 97.1-100 and 96.3-100 respectively) and the specificity 33% (95 % CI: 25.7-38.1). With 4 microg/ml, the corresponding figures were 98.4 (95% CI: 94.4-99.8), 98.3 (95% CI: 94.1-99.8) and 39% (95% CI: 33.6-44.7) respectively. The prevalence of PE was 30%, the exclusion rates were 23 and 27% for either cut-off. When compared with a reference D-dimer assay (Asserachrom D-Di), a good correlation was observed. In conclusion, this is the first study suggesting the interest of this Fibrin Monomer test to rule out PE; these results, however, need to be confirmed by other studies.     

Appropriateness of diagnostic strategies for evaluating suspected venous thromboembolism

It was the objective of this study to determine the proportion of patients who undergo an appropriate diagnostic work-up following a D-dimer test performed to evaluate suspected pulmonary embolism (PE) or deep vein thrombosis (DVT). We performed a retrospective cohort study at a tertiary care hospital. We included patients if they underwent D-dimer testing between 2002 and 2005, if the D-dimer was performed for evaluation of VTE, and if the D-dimer test was successful. We classified: the patients' clinical probability of DVT or PE according to the Wells models, the imaging results, and the appropriateness of the testing algorithm. Of 1,000 randomly selected patients, 863 met our study criteria. Seven hundred nineteen patients (83%) had testing during an emergency department visit, while 144 were tested as inpatients (17%). Physicians performed the D-dimer test to evaluate DVT and PE in 238 (28%) and 625 (72%) patients, respectively. Overall, the testing strategy was appropriate in 69% (95% confidence interval [CI]: 66%-72%) of cases. The testing strategy was more likely to be appropriate for emergency department versus inpatients (75% vs. 39%, p < 0.05) and for DVT versus PE patients (84% vs. 63%, p < 0.05). Of all in-appropriately tested patients, under-utilization of diagnostic imaging was more common than over-utilization (90% vs. 10%, p < 0.05). VTE was confirmed in 37 of 138 'DVT patients' and 35 of 625 'PE patients' (16% [95% CI: 11%-21%] and 6% [95% CI: 4%-8%], respectively). In conclusion, physicians often fail to use diagnostic testing strategies for VTE correctly following a D-dimer test.     

A positive compression ultrasonography of the lower limb veins is highly predictive of pulmonary embolism on computed tomography in suspected patients

The presence of a clot-- even asymptomatic-- in the proximal lower limb veins of a patient with clinically suspected pulmonary embolism (PE) provides evidence for venous thromboembolism and indicates anticoagulant therapy in such patients. We aimed at assessing the diagnostic performance of compression ultrasonography as compared to multi-slice computed tomography (MSCT) for the diagnosis of PE. We analyzed data from a large outcome management study that included consecutive outpatients referred to the emergency ward with clinically suspected PE. All high clinical probability patients, and all non-high clinical probability patients with a positive D-dimer test underwent both MSCT and CUS. Of the 756 included patients, 232 had PE ruled out on the basis of a negative D-dimer test, and 524 patients underwent both MSCT and CUS. PE was found in 187 out of the 511 patients with a conclusive MSCT. The sensitivity of CUS for the presence of PE on MSCT was 39% (95% confidence interval: 32 to 46%), and its specificity was 99% (95% CI:97 to 100%). Positive and negative likelihood ratios were 42.2 (95% CI: 13.5 to 131.9) and 0.6 (95% CI: 0.5 to 0.7), respectively. We conclude from that large study of unselected patients that CUS has high specificity but low sensitivity, for the diagnosis of PE at MSCT in suspected patients. It allows ruling in the diagnosis of PE without further invasive and/or expensive testing in suspected patients.     

Exclusion of pulmonary embolism using C-reactive protein and D-dimer. A prospective comparison

Our goal was to evaluate the diagnostic utility of C-reactive protein (CRP) alone or combined with clinical probability assessment in patients with suspected pulmonary embolism (PE), and to compare its performance to a D-dimer assay. We conducted a prospective study in which we performed a common immuno-turbidimetric CRP test and a rapid enzyme-linked immunosorbent assay (ELISA) D-dimer test in 259 consecutive outpatients with suspected PE at the emergency department of a teaching hospital. We assessed clinical probability of PE by a validated prediction rule overridden by clinical judgment. Patients with D-dimer levels > or = 500 microg/l underwent a work-up consisting of lower-limb venous ultrasound, spiral computerized tomography, ventilation-perfusion scan, or pulmonary angiography. Patients were followed up for three months. Seventy-seven (30%) of the patients had PE. The CRP alone had a sensitivity of 84% (95% confidence interval [CI).: 74 to 92%) and a negative predictive value (NPV) of 87% (95% CI: 78 to 93%) at a cutpoint of 5 mg/l. Overall, 61 (24%) patients with a low clinical probability of PE had a CRP < 5 mg/l. Due to the low prevalence of PE (9%) in this subgroup, the NPV increased to 97% (95% CI: 89 to 100%).The D-dimer (cutpoint 500 micro g/l) showed a sensitivity of 100% (95% CI: 95 to 100%) and a NPV of 100% (95% CI: 94 to 100%) irrespective of clinical probability and accurately rule out PE in 56 (22%) patients. Standard CRP tests alone or combined with clinical probability assessment cannot safely exclude PE.     

High utilization rate of vena cava filters in deep vein thrombosis

The objective was to investigate newly diagnosed patients with deep vein thrombosis (DVT) who received inferior vena cava filters (IVCFs). A prospective registry enrolled 5451 patients from 183 US study sites. In all patients, examination by venous duplex ultrasound confirmed the diagnosis of DVT. We collected and analyzed data on 781 patients who received an IVCF. The most frequently prescribed treatments were low-molecular-weight heparin and unfractionated heparin, which were used as a bridge to warfarin in 39% (n=2143) and 35% (n=1926) of patients, respectively. Of the total population, 781 (14%) (235 outpatients, 546 inpatients) underwent IVCF placement. The most common reasons for IVCF placement were contraindication to anticoagulation (n = 271), prophylaxis (n = 259), major bleeding related to anticoagulation therapy (n = 92), and anticoagulation failure (n = 73). Multivariate analysis revealed that patients were more likely to undergo IVCF insertion with multiple system organ failure (odds ratio [OR], 3.6; 95% CI, 1.48-8.60), previous stroke (OR,3.2;95% CI,2.11-4.74), or history of pulmonary embolism (OR,2.4; 95% CI, 1.95-2.91). In conclusion, a surprisingly high 14% (781) of patients with confirmed DVT received an IVCF. Many of these patients may have warranted less invasive methods of venous thromboembolism prophylaxis. Improved physician education regarding mechanical and pharmacologic prophylaxis alternatives might reduce the use of IVCFs.     

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.     

Sensitive and quantitative, 10-min immunofluorometric assay for D-Dimer in whole blood

INTRODUCTION: Normal concentrations of D-Dimer can be used to exclude venous thromboembolism (VTE). However, methods for sensitive and quantitative D-Dimer measurements at the point-of-care (POC) are still limited. MATERIALS AND METHODS: We developed a 10-min, non-competitive immunofluorometric assay for D-Dimer in citrated whole blood and plasma using pre-dispensed reagents dried in single assay wells. The simple, automated assay procedure comprises a 1:50 sample dilution, one-step incubation, washing, and time-resolved fluorometric measurement directly from the wet well surface. RESULTS: The limits of detection (background + 3SD) and quantification (CV <15%) were 0.05 and 0.2 mg/L D-Dimer, respectively, and the assay was linear up to 400 mg/L. Correlations to Roche TinaQuant (r=0.726, n=200) and Biopool Auto.Dimer (r=0.190, n=149) were carried out using citrated plasma. Diagnostic sensitivity, specificity, and negative (NPV) and positive (PPV) predictive values were 98.7%, 64.4%, 99.1% and 55.1%, and 92.2%, 81.0%, 95.9% and 68.3%, respectively, using cut-off values of 0.6 and 1.0 mg/L, respectively, in outpatients with deep vein thrombosis (DVT) and/or pulmonary embolism (PE) (n=77) compared with outpatients with various other diseases (n=174). The within- and between-run CVs near the cut-off values were < or =10% in both whole blood and plasma. The 95th percentile upper range in apparently healthy individuals was 0.68 mg/L of whole blood (n=101). CONCLUSIONS: The high sensitivity and NPV suggest that the rapid immunofluorometric assay could be valuable for rapid exclusion of VTE in outpatients. With appropriate cut-offs, the assay could potentially be used as a stand-alone test or combined with clinical probability assessment, but further studies are required.     

Evaluation of advanced D-dimer assay for the exclusion of venous thromboembolism

The performances for thromboembolic disease exclusion of a new microlatex-enhanced D-dimer immunoassay have been evaluated. Advanced D-dimer (Dade-Behring, Marburg, Germany) was tested with two automated analyzers, namely BCS and CA-1500. Precision studies yielded coefficients of variation (within-run and run-to-run) of 3% and 6.3% at D-dimer levels near the cut-off value, for BCS and CA-1500 respectively. Frozen samples from 294 consecutive symptomatic outpatients suspected of either deep venous thrombosis (140) or pulmonary embolism (154) from a previous management study were tested with both analyzers, as well as with the VIDAS New assay (BioMerieux, Marcy-l'Etoile, France). For BCS, sensitivity and specificity were 96.6% (95% CI, 90.5, 99.3) and 42% (35.1, 49.0) respectively at a cut-off value of 1.35 microg/ml. For CA-1500, the corresponding figures were 95.5% (88.9, 98.8) and 47.8% (40.8, 54.9) at a cutt-off value of 1.1 microg/ml. This assay appears promising and should be validated in clinical practise to assess its place in the work-up schemes of thromboembolism.     

The performance of two rapid quantitative D-dimer assays in 287 patients with clinically suspected pulmonary embolism

Context: Objective tests are necessary for the diagnosis of pulmonary embolism (PE). D-dimer assays have been suggested as useful screening tests to exclude this diagnosis. Objective: To compare the diagnostic accuracy of two rapid quantitative D-dimers in patients with suspected pulmonary embolism. Design: Plasma D-dimer levels were measured using two commercially available assays (Tinaquant® and Vidas®). A strict imaging protocol was used to arrive at a final diagnosis of PE or deep venous thrombosis (DVT). Setting: Multicenter study in six Dutch referral centers. Patients: A total of 287 in- and outpatients with clinically suspected pulmonary embolism. Main outcome measures: Diagnostic accuracy indices for the two assays were calculated and additional receiver-operated characteristics (ROC) analysis was performed. Results: Using the manufacturer's advised cutoff values, the sensitivity and specificity were 88% and 52% for Vidas and 82% and 61% for Tinaquant, respectively. These differences were statistically significant (McNemar, P<0.0001). However, no statistical differences were found between the two assays using ROC analysis (AUC=0.78 for both assays). Conclusions: Both quantitative D-dimer tests had similar diagnostic accuracy; however, at the manufacturer's advised cutoff level, Vidas performed significantly better. Nevertheless, to safely exclude pulmonary embolism, D-dimer assays should be combined with other diagnostic tests.     

Combined use of clinical pre-test probability and D-dimer test in the diagnosis of preoperative deep venous thrombosis in colorectal cancer patients

The preoperative prevalence of deep venous thrombosis (DVT) in patients with colorectal cancer may be as high as 8%. In order to minimize the risk of pulmonary embolism, it is important to rule out preoperative DVT. A large study has confirmed that a negative D-dimer test in combination with a low clinical pre-test probability (PTP) can be safely used to rule out the tentative diagnosis of DVT in cancer patients. However, the accuracy in colorectal cancer patients is uncertain. This study assessed the diagnostic accuracy of a quantitative D-dimer assay in combination with the PTP score in ruling out preoperative DVT in colorectal cancer patients admitted for surgery. Preoperative D-dimer test and compression ultrasonography for DVT were performed in 193 consecutive patients with newly diagnosed colorectal cancer. Diagnostic accuracy indices of the D-dimer test were assessed according to the PTP score. The negative predictive value, positive predictive value, sensitivity and specificity were 99% (95% confidence interval (CI), 95-100%), 17% (95% CI, 9-26), 93% (95% CI, 68-100%) and 61% (95% CI, 53-68%), respectively. In conclusion, the combined use of pre-test probability and D-dimer test may be useful in ruling out preoperative DVT in colorectal cancer patients admitted for surgery.     

Derivation of a simple clinical model to categorize patients probability of pulmonary embolism: increasing the models utility with the SimpliRED D-dimer

We have previously demonstrated that a clinical model can be safely used in a management strategy in patients with suspected pulmonary embolism (PE). We sought to simplify the clinical model and determine a scoring system, that when combined with D-dimer results, would safely exclude PE without the need for other tests, in a large proportion of patients. We used a randomly selected sample of 80% of the patients that participated in a prospective cohort study of patients with suspected PE to perform a logistic regression analysis on 40 clinical variables to create a simple clinical prediction rule. Cut points on the new rule were determined to create two scoring systems. In the first scoring system patients were classified as having low, moderate and high probability of PE with the proportions being similar to those determined in our original study. The second system was designed to create two categories, PE likely and unlikely. The goal in the latter was that PE unlikely patients with a negative D-dimer result would have PE in less than 2% of cases. The proportion of patients with PE in each category was determined overall and according to a positive or negative SimpliRED D-dimer result. After these determinations we applied the models to the remaining 20% of patients as a validation of the results. The following seven variables and assigned scores (in brackets) were included in the clinical prediction rule: Clinical symptoms of DVT (3.0), no alternative diagnosis (3.0), heart rate >100 (1.5), immobilization or surgery in the previous four weeks (1.5), previous DVT/PE (1.5), hemoptysis (1.0) and malignancy (1.0). Patients were considered low probability if the score was <2.0, moderate of the score was 2.0 to 6.0 and high if the score was over 6.0. Pulmonary embolism unlikely was assigned to patients with scores < or =4.0 and PE likely if the score was >4.0. 7.8% of patients with scores of less than or equal to 4 had PE but if the D-dimer was negative in these patients the rate of PE was only 2.2% (95% CI = 1.0% to 4.0%) in the derivation set and 1.7% in the validation set. Importantly this combination occurred in 46% of our study patients. A score of <2.0 and a negative D-dimer results in a PE rate of 1.5% (95% CI = 0.4% to 3.7%) in the derivation set and 2.7% (95% CI = 0.3% to 9.0%) in the validation set and only occurred in 29% of patients. The combination of a score < or =4.0 by our simple clinical prediction rule and a negative SimpliRED D-Dimer result may safely exclude PE in a large proportion of patients with suspected PE.     

Evaluation of plasma D-dimer in the diagnosis and in the course of fibrinolytic therapy of deep vein thrombosis and pulmonary embolism.

Blood samples were obtained from patients with deep venous thrombosis (DVT) or pulmonary embolism (PE) after angiographic confirmation as well as during fibrinolytic therapy with streptokinase. Plasma cross-linked fibrin degradation products were measured by a quantitative enzyme-linked immunoassay that recognizes the D-Dimer epitope. 24 patients with PE showed elevated D-Dimer levels (median; 25%-, 75%-quartile) (3,250 ng/ml; 1,270 ng/ml, 6,940 ng/ml) as well as 38 patients presenting with DVT (2,330 ng/ml; 1,760 ng/ml, 3,980 ng/ml). The sensitivity for the diagnosis of PE was 92%, for diagnosis of DVT 89% resp. 100%, depending on the cut-off limit. The D-Dimer level showed a correlation (r = 0.64) to the angiographically documented severity of PE quantified by the Miller's score, in contrast to DVT, where no such correlation could be found. During fibrinolytic therapy median levels rose from 3,020 ng/ml to 63,000 ng/ml within 8 hours and then fell within 6 days to 2,930 ng/ml. 10 patients with PE showed a good correlation (r = 0.72) between the reduction of Miller's score within 72 hours and D-Dimer 24 hours after the onset of therapy. In 17 patients with fibrinolytic treatment of DVT no correlation between D-Dimer and clot lysis could be found. These findings indicate that D-Dimer can provide additional information in the diagnostic procedure of suspected PE. During fibrinolytic therapy of PE with streptokinase, D-Dimer could serve as an early prognostic parameter of successful thrombolysis.     

Antipsychotic and antidepressant drug use in the elderly and the risk of venous thromboembolism

BACKGROUND: Preliminary evidence suggests that use of antipsychotic drugs is associated with an increased risk of venous thromboembolism. OBJECTIVE: To evaluate the relationship between antipsychotic or antidepressant drug use and venous thromboembolism among adults aged 65 years and older. DESIGN: Retrospective cohort study using linked health care administrative databases over a nine year period. SETTING: The entire province of Ontario, Canada. PARTICIPANTS: Individuals aged 65 years and over exclusively prescribed either antipsychotic drugs (n = 22,514), antidepressant drugs (n = 75,649) or thyroid replacement hormones (33,033), the referent control group. We excluded those with an antecedent history of cardiovascular disease, venous thromboembolism or cancer, as well as those dispensed warfarin before study entry. MEASUREMENTS: Diagnosis of deep vein thrombosis or pulmonary embolism. RESULTS: Relative to those prescribed thyroid hormones, neither antidepressant (adjusted hazard ratio 1.02, 95% CI 0.91-1.14) nor antipsychotic (adjusted hazard ratio 1.13, 95% CI 0.96-1.32) drug use was associated with an increased risk for deep vein thrombosis. Similar risk estimates were found for deep vein thrombosis or pulmonary embolism. In a sub-group analysis, only butyrophenone use was found to be associated with a slightly increased risk of deep vein thrombosis (adjusted HR 1.51, 95% CI 1.23-1.86) as well as deep vein thrombosis or pulmonary embolism (adjusted HR 1.43, 95% CI 1.18-1.74). CONCLUSIONS: In a large cohort of adults aged 65 years and older, neither antipsychotic or antidepressant drug use was associated with an increased risk of venous thromboembolism, with the exception of a slightly increased risk among those prescribed butyrophenones. Further data are required before use of these psychoactive drugs can be considered a risk factor for venous thromboembolism.     

Results of a new rapid d-dimer assay (cardiac d-dimer) in the diagnosis of deep vein thrombosis.

The objective was to evaluate the accuracy of a new full blood rapid D-dimer assay in the diagnosis of suspected deep vein thrombosis (DVT). In 100 consecutive patients with suspected DVT, clinical probability was staged according to a pretest score proposed by Wells. For the determination of plasma D-dimer, heparin and citrate blood samples were drawn, and Cardiac D-dimer, STA-LIA, and Tina-quant tests were performed. Final diagnosis was confirmed either by duplex sonography or ascending venography. DVT was diagnosed in 37%, thrombophlebitis in 10%, and no venous thromboembolism was diagnosed in 52%. In 2% pulmonary embolism was detected and one patient was dismissed before final diagnosis. Cardiac D-dimer assay from citrate tubes showed a sensitivity of 88.6%, a specificity of 54%, a positive predictive value of 57.4%, and a negative predictive value of 87.1%. Nearly identical results were observed with heparin tubes. Corresponding results were 88.6%, 48%, 52.5%, and 85.7% for STA-LIA and 88.6%, 46%, 53.4%, and 85.2% for Tina-quant, respectively. In conclusion, we can say that Cardiac D-dimer is a rapid, whole blood assay with a great potential for clinical use. It can help in diagnosing DVT from citrate as well as heparin tubes with comparable sensitivity, specificity, positive and negative predictive values as STA-LIA and Tina-quant tests.     

Outpatient treatment of pulmonary embolism with dalteparin

BACKGROUND: Pulmonary embolism is a common complication of deep vein thrombosis. It has been established that low molecular weight heparin may be used to treat deep vein thrombosis or pulmonary embolism and randomized studies have established that outpatient management of deep vein thrombosis with low molecular weight heparin is at least as effective as in-hospital management with unfractionated heparin. METHODS: This was a prospective cohort study of eligible patients with pulmonary embolism managed as outpatients using dalteparin (200 U/kg s/c daily) for a minimum of five days and warfarin for 3 months. Outpatients included those managed exclusively out of hospital and those managed initially for 1-3 days as inpatients who then completed therapy out of hospital. Reasons for admission included hemodynamic instability; hypoxia requiring oxygen therapy; admission for another medical reason; severe pain requiring parenteral analgesia or high risk of major bleeding. Patients were followed for three months for clinically apparent recurrent venous thromboembolism and bleeding. RESULTS: Between three teaching hospitals, a total of 158 patients with pulmonary embolism were identified. Fifty patients were managed as inpatients and 108 as outpatients. Of the outpatients, 27 were managed for an average of 2.5 days as inpatients and then completed dalteparin therapy as outpatients. The remaining 81 patients were managed exclusively as outpatients with dalteparin. For all outpatients the overall symptomatic recurrence rate of venous thromboembolism was 5.6% (6/108) with only 1.9% (2/108) major bleeds. There were a total of four deaths with none due to pulmonary embolism or major bleed. CONCLUSIONS: This prospective study suggests that outpatient management of pulmonary embolism is feasible and safe for the majority of patients.     

Incidence of post-thrombotic syndrome in patients with previous pulmonary embolism. A retrospective cohort study

There is little information available about the true incidence of post-thrombotic syndrome (PTS) after pulmonary embolism (PE). The aim of this study was to investigate the incidence of PTS in patients with previous pulmonary embolism without concomitant ultrasonographically-detectable deep vein thrombosis (DVT). A retrospective cohort study was conducted at a single tertiary care centre, Cosenza, Italy. Forty-seven consecutive patients with proved PE without DVT within the previous 2 to 6 years, 45 patients with previous DVT in the same years, and 45 patients with diseases unrelated to venous thromboembolism (VTE) underwent a blind assessment for PTS using a clinical score. Two of 47 (4.2%, 95%CI: 0.01-9.9) patients with PE, 2 of 45 (4.4%, 95%CI: 0.01-10.4) patients with diseases unrelated to VTE, and 23 of 45 (53.3%, 95%CI: 38.7-67.9) patients with DVT showed signs and symptoms of PTS. The difference between the first two groups was not statistically significant (p = 0.7). In conclusion, the incidence of PTS after pulmonary embolism without DVT is low, and no different from that of patients without previous VTE.     

Is the prevalence of the factor V Leiden mutation in patients with pulmonary embolism and deep vein thrombosis really different?

INTRODUCTION: Previous investigations have suggested a lower prevalence of the factor V Leiden mutation in patients with pulmonary embolism, as compared to patients with deep leg vein thrombosis. METHODS: We studied unselected patients with pulmonary embolism, in whom we also assessed the presence of deep vein thrombosis by ultrasonography. We assessed the prevalence of heterozygosity for the factor V Leiden mutation and compared the outcome of patients with a normal ultrasound (primary pulmonary embolism) to those with an abnormal ultrasound (combined form of venous thromboembolism). Furthermore, we performed a literature search to identify all articles regarding the prevalence of heterozygous factor V Leiden mutation in patients with primary deep vein thrombosis, primary pulmonary embolism and a combined form of venous thromboembolism. We calculated a (common) odds ratio for these 3 manifestations of venous thromboembolism, including the current findings. RESULTS: In 92 patients with proven pulmonary embolism, 25 (27%) had also an abnormal ultrasound. In these patients, the prevalence of the factor V Leiden mutation was 24% (95% CI 9%-45%), whereas the mutation was present in 5 of 67 patients with primary pulmonary embolism (7%; 95% CI 2%-16%). The literature analysis indicated the common odds ratio for the presence of heterozygous factor V Leiden mutation in patients with primary deep vein thrombosis, primary pulmonary embolism and the combined form of venous thromboembolism to be 7.9 (95% CI 5-12), 3.5 (95% CI 2-6) and 6.8 (95% CI 3-14), respectively. CONCLUSION: In patients with primary pulmonary embolism the prevalence of the factor V Leiden mutation appears to be half of that reported in patients with primary deep vein thrombosis. The mechanism remains unclear.