D-dimer Cut-off Value Research Articles

Combined use of pretest clinical probability score and latex agglutination D-dimer testing for excluding acute deep vein thrombosis

Currently, the latex agglutination D-dimer assay is widely used for excluding deep vein thrombosis (DVT) but is considered less sensitive than the enzyme-linked immunosorbent assay-based D-dimer test. The purpose of the present study was to determine if a combination of different cutoff points, rather than a single cutoff point of 1.0 microg/mL, on the latex agglutination D-dimer assay and the pretest clinical probability (PTP) score would be able to reduce the use of venous duplex ultrasound (DU) scanning in patients with suspected DVT. The PTP score and D-dimer testing were used to evaluate 989 consecutive patients with suspected DVT before venous DU scanning. After calculating the clinical probability scores, patients were divided into low-risk (< or =0 points), moderate-risk (1-2 points), and high-risk (> or =3 points) pretest clinical probability groups. Receiver operating characteristic (ROC) curve analysis was used to determine the appropriate D-dimer cutoff point for each PTP with a negative predictive value of >98% for a positive DU scan. There were 886 patients enrolled. The study group included 609 inpatients (68.7%) and 277 outpatients (31.3%). The prevalence of DVT in this series was 28.9%. There were 508 patients (57.3%) classified as low-risk, 237 (26.8%) as moderate-risk, and 141 (14.9%) as high-risk PTP. DVT was identified in 29 patients (5.7%) with low-risk, 118 (49.8%) with moderate-risk, and 109 (77.3%) with high-risk PTP scores. ROC curve analysis was used to select D-dimer cutoff points of 2.6, 1.1, and 1.1 microg/mL for the low-, moderate- and high-risk PTP groups, respectively. In the low-risk PTP group, specificity increased from 48.9% to 78.2% (P < .0001) with use of the different D-dimer cutoff value. In the moderate- and high-risk PTP groups, however, the different D-dimer levels did not achieve substantial improvement. Despite this, the overall use of venous DU scanning could have been reduced by 43.0% (381 of 886) if the different D-dimer cutoff points had been used. Combination of a specific D-dimer level with the clinical probability score is most effective in low-risk PTP patients for excluding DVT. In moderate- and high-risk PTP patients, however, the recommended cutoff points of 1.0 microg/mL may be preferable. These results show that different D-dimer levels for patients differing in risk is feasible for excluding DVT using the latex agglutination D-dimer assay.

Cut-off values of D-dimer and soluble fibrin for prediction of deep vein thrombosis after orthopaedic surgery

Soluble fibrin (SF) and D-dimer are considered to be useful for the diagnosis of thrombosis; however, the efficacy of the diagnosis of deep vein thrombosis (DVT) after orthopaedic surgery by SF and D-dimer is still not well established. The present study was designed to evaluate the efficacy of SF and D-dimer in the diagnosis of DVT after orthopaedic surgery. The plasma concentrations of SF and D-dimer were measured in 99 patients following orthopaedic surgery. The plasma concentrations of D-dimer and SF in patients undergoing orthopaedic surgery were markedly high in comparison to healthy volunteers, and these markers were increased after surgery. The plasma concentrations of D-dimer were significantly higher in patients with DVT than in those without DVT at days 4, 7, 10 and 14, and those of SF were significantly higher in patients with DVT than in those without DVT at days 1, 4 and 14. A receiver operating characteristic (ROC) analysis of SF and D-dimer for diagnosis of DVT after surgery generated an ROC curve that showed SF to be better than D-dimer at day 1, while D-dimer was better than SF at day 4. In addition, less than 7.2 microg/ml of D-dimer or 3.6 microg/ml of SF at day 1 after surgery, or less than 7.0 microg/ml of D-dimer at day 4 excluded DVT. These findings suggest that the D-dimer and SF are useful for the diagnosis and exclusion of DVT after orthopaedic surgery.

D-dimer and Factor VIII are Independent Risk Factors for Recurrence After Anticoagulation Withdrawal for a First Idiopathic Deep Vein Thrombosis

Conclusion: Elevated levels of D-dimer and factor VIII at 30 ± 10 days after cessation of vitamin K antagonist (VKA) therapy for a first episode of idiopathic proximal deep venous thrombosis (DVT) are independent risk factors for recurrent venous thromboembolism (VTE). Summary: The optimal duration of VKA therapy after a first episode of VTE is unknown. It appears VKA extension after unprovoked VTE can reduce the risk of recurrent VTE but at the potential price of increased bleeding. There is therefore intense interest in stratifying patients with idiopathic VTE with respect to risk factors that may increase rates of recurrence. The specific objective of this study was to assess the risk of recurrence of VTE associated with elevated D-dimer levels and factor VIII levels after withdrawal of VKA therapy for symptomatic idiopathic proximal VTE. Consecutive outpatients with the first episode of idiopathic proximal DVT were enrolled into the study after cessation of VKA therapy. At 30 ± 10 days after cessation of VKA therapy, levels of D-dimer (cutoff value, 500 ng/mL) and chromogenic factor VIII, as well as inherited thrombophilias were determined. Follow-up extended for 2 years. Overall recurrence rate of VTE was 16.4% (55 of 336; 95% confidence interval [CI], 13%-21%). The multivariate hazard ratio for recurrence was 2.45 (95% CI, 1.24-4.99) for abnormal D-dimer and 2.76 (95% CI, 1.57-4.85) for factor VIII >75th percentile (2.42 μ/mL). The values were adjusted for age, sex, and thrombophilia. Compared with normal levels of D-dimer and factor VIII, the multivariate hazard ratio was 4.5 (95% CI, 1.7-12.2) for normal D-dimer levels with factor VIII >2.42 U/mL, and 2.7 (95% CI, 1.2-6.6) and 7.1 (95% CI, 2.8-17.6) for abnormal D-dimer with factor VIII, respectively, below and above 2.42 U/mL. Comment: The appropriate length of treatment with VKA therapy for patients with idiopathic VTE is unknown. The data suggest the longer the treatment period with VKA, the less the recurrence rates of VTE. Of course, VKAs are associated with increased risk of bleeding and are inconvenient for the patient. There is therefore intense interest in stratifying risk among those patients with idiopathic VTE. This is another study that attempts to do just that. The percentage of patients with both normal D-dimer and factor VIII <75th percentile was 37%. This implies that at least a third of patients with idiopathic VTE have a low risk of VTE recurrence. Larger studies are warranted to determine if the combination of factor VIII and D-dimer analysis can be used to tailor duration of VKA therapy after idiopathic VTE.

Cut-off value of D-dimer in pulmonary thromboembolism and pneumonia

Aim: The differential diagnosis of pulmonary thromboembolism (PTE) and pneumonia remains difficult in emergency rooms. High D-dimer levels in the pneumonia may be misdiagnosed as PTE on the basis of similar clinical, radiological, and laboratory findings. Since D-dimer elevation may also be seen in pneumonia cases, the comparison of D-dimer values in patients diagnosed as pneumonia and PTE, in order to determine a cut-off value between the 2 diseases, was aimed in this study. Materials and methods: Patients in the community acquired pneumonia (CAP) group were classified according to the American Thoracic Society (ATS) 2001 criteria. Groups III and IV patients, who were hospitalized, were included in the study. The final CAP group consisted of 52 patients (30 in Group IIIa, 15 in Group IIIb, 2 in Group IVa, and 5 in Group IVb) and 68 patients with a diagnosis of PTE. All patients’ D-dimer levels in the first day were recorded. Results: Mean D-dimer levels of the PTE and pneumonia group were 4868 ng/mL and 2068 ng/mL, respectively (P < 0.001). Cut-off value was 4374 ng/mL. Mean levels of D-dimer in the massive PTE group and sub-massive PTE group were 5438 ng/mL and 4175 ng/mL,respectively, (P = 0.04). Conclusion: Elevation of D-dimer is more significant in PTE than pneumonia. As a result, if D-dimer level is higher than 4374 ng/mL, the patient should be evaluated for the diagnosis of PTE. A cut-off value of 4374 ng/mL will help the discrimination of PTE and pneumonia.

Cutoff Values of D-Dimer and FDP in Plasma for the Diagnosis of Thrombosis

Cutoff Values of D-Dimer and FDP in Plasma for the Diagnosis of Thrombosis

Cutoff Values of D-Dimer and FDP in Plasma for the Diagnosis of Thrombosis

Cutoff Values of D-Dimer and FDP in Plasma for the Diagnosis of Thrombosis

Evaluation of haemostatic molecular markers for diagnosis of disseminated intravascular coagulation in patients with infections

Early treatment of disseminated intravascular coagulation (DIC) is recommended but global coagulation tests used in authorized DIC criteria are not sensitive for diagnosis of early-phase DIC. We examined the plasma levels of thrombin-antithrombin complex (TAT), plasmin-plasmin inhibitor complex (PPIC) and D-dimer in patients with suspected DIC to determine the cutoff values for diagnosis of DIC. Plasma levels of D-dimer, TAT and PPIC were significantly elevated in patients with DIC and correlated with DIC score. The cutoff values were determined using the receiver operative curve analysis. The cutoff value represented the point at which the sensitivity curve crossed the specificity curve. The cutoff values of D-dimer, TAT and PPIC for DIC were 12.0 mug/ml, 11.0 ng/ml and 1.8 mug/ml, respectively. These values were moderately to highly sensitive for the diagnosis of DIC but not for poor outcome. The combination of D-dimer, TAT and PPIC showed high sensitivity and low specificity when one or more tests were positive, but showed low sensitivity and high specificity when all three tests were positive. We conclude that hemostatic molecular markers might be useful for the diagnosis of DIC and should be confirmed by several trials.

Clinical usefulness of D-dimer testing in cancer patients with suspected pulmonary embolism

Limited data are available about the diagnostic value of D-dimer testing in cancer patients with clinically suspected pulmonary embolism (PE). Therefore, we evaluated i) the safety and clinical usefulness of an ELISA D-dimer test to rule out PE in cancer patients compared with non-cancer patients and ii) whether adopting a higher D-dimer cut-off value might increase the usefulness of D-dimer in cancer patients. We analysed data from two outcome studies which enrolled 1,721 consecutive patients presenting in the emergency department with clinically suspected PE. Presence of an active malignancy was abstracted from the database. All patients underwent a sequential diagnostic work-up including an ELISA D-dimer test and a 3-month followup. Sensitivity and predictive value (NPV) were 100% in both cancer and non-cancer patients. PE was ruled out by a negative D-dimer test in 494/1,554 (32%) patients without cancer, and in 18/164 (11%) patients with a malignancy. At cut-off values varying from 500 to 900 microg/l, the sensitivity was unchanged (100%, 95% CI: 93% to 100%) and the specificity increased from 16% (95% CI: 11% to 24%) to 30% (95% CI: 22% to 39%). The 3-month thromboembolic risk was 0% (95% CI: 0% to 18%) in cancer patients with a negative D-dimer test. ELISA D-dimer appears safe to rule out pulmonary embolism in cancer patients but it is negative in only one of ten patients at the usual cut-off value. Increasing the cut-off value of D-dimer in cancer patients might increase the test's clinical usefulness.

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

Venous thromboembolism in colorectal cancer patients with central venous catheters for 5-FU infusion-based pharmacokinetic modulating chemotherapy

Colorectal cancer patients with central venous catheters (CVC) for pharmacokinetic modulating chemotherapy (PMC) have a substantial risk of venous thromboembolism (VTE). PMC, designed as a hybrid of lower metronomic and higher shorter plasma 5-FU concentrations, has been clinically successful. To determine the effectiveness and safety of D-dimer tests and multidetector-row CT (MDCT) for diagnosis in cancer patients with suspected VTE, we carried out a clinical outcome study on PMC outpatients. Patients received a D-dimer test before and after commencing the PMC regimen. MDCT was performed additionally if the D-dimer test appeared positive or showed signs of VTE. When CT results were positive for thromboembolism, anticoagulation was started. The overall prevalence of VTE in PMC patients was 2.0% (7 of 350 patients). In this study, 34 out of 102 colorectal cancer patients gave a positive D-dimer test (33.3%). CT identified venous thrombi in 2 of the 102 patients (2.0%), mural thrombosis on catheterized veins in another 3 patients (2.9%), and endothelial hyperplasia on catheterized veins in 8 patients (7.8%). The catheters of these patients did not show any significant abnormalities. Patients with negative D-dimer tests showed no signs or symptoms of VTE. In colorectal cancer patients receiving continuous 5-FU infusion via CVC, a D-dimer test can be safely used as the primary diagnostic test for ruling out VTE. We suggest 7.0 microg/ml as the D-dimer cut-off value. Thromboprophylaxis should be considered in the patients showing values >7.0 microg/ml.

D-dimer levels in combination with residual venous obstruction and the risk of recurrence after anticoagulation withdrawal for a first idiopathic deep vein thrombosis

We assessed the predictive value of D-dimer levels in combination with residual venous obstruction (RVO) for recurrent venous thromboembolism (VTE) in a prospective cohort of outpatients after oral anticoagulant therapy (OAT) suspension for a first episode of idiopathic proximal deep vein thrombosis of the lower limbs during a 2-year follow-up. Patients (n=400) were enrolled on the day of OAT suspension when RVO was determined by compression ultrasonography (present in 48.6% of patients). D-dimer (cut-off value: 500 ng/mL) was measured 30+/-10 days afterwards (abnormal in 56.4% of patients). The overall recurrence rate was 16.7% (67/400; 95% confidence intervals - CI -: 13-21 %). The multivariate hazard ratio (HR) for recurrence was 3.32 (95% CI: 1.78-6.75; p<0.0001) for abnormal D-dimer compared to normal D-dimer and 1.2 (95% CI:0.72-2.07; p>0.05) for RVO compared to absent RVO. The recurrence rate was 5.7% (95% CI:2-13%) and 10.4% (95% CI:6-18%), respectively, for normal D-dimer either without or with RVO, 22.9% (95% CI: 14-33%) and 25.9% (95% CI: 18-35%), respectively, for abnormal D-dimer, either without or with RVO. When compared with normal D-dimer without RVO, the multivariate HR for recurrence was similar for abnormal D-dimer either with RVO (4.76 - 95% CI:1.78-12.8) or without RVO (4.3-95%:1.56-11.88). Abnormal D-dimer at one month after OAT withdrawal is an independent risk factor for recurrent VTE, while RVO at the time of OAT withdrawal, either with normal or abnormal D-dimer after one month, does not influence the risk of recurrence.

Diagnosis of deep vein thrombosis by plasma-soluble fibrin or D-dimer

The present study was designed to determine the cutoff values of D-dimer and soluble fibrin (SF) for the diagnosis of deep venous thrombosis (DVT) and pulmonary embolism (PE) in Japanese patients. Plasma levels of these molecules were measured in 243 patients suspected of having DVT and 100 healthy volunteers (controls). Out of 243 patients, 20 patients were diagnosed with DVT. In the control group, plasma levels of D-dimer and SF did not show normal distribution, and the 95% confidence intervals (CI) of D-dimer and SF were 2.45 microg/mL and 6.92 microg/mL, respectively. Plasma levels of D-dimer and SF of patients with DVT were significantly higher than of those without DVT. In patients with DVT, the minimum values of D-dimer and SF were 1.71 and 1.44 microg/mL, respectively. When the cutoff value was set at the average+1 SD of those of the control (D-dimer, about 1.8 microg/mL; SF, about 1.4 microg/mL), 1 and 0 patient with DVT was overlooked, respectively. The sensitivity and specificity of D-dimer and SF for DVT were 95% and 100%, and 61.9% and 53.8%, respectively. When the cutoff value was set at 95% CI of the control (D-dimer, 2.5 microg/mL; SF, 6.9 microg/mL), 2 and 9 patients with DVT were overlooked, respectively. The sensitivity and specificity of D-dimer and SF were 90% and 50%, and 77.6% and 88.3%, respectively. When the cutoff values set at 2.5 microg/mL of D-dimer or 6.9 microg/mL of SF, 1 DVT patient was overlooked, with sensitivity and specificity of 95% and 69.5%. Our data suggest that both D-dimer and SF are useful markers for the diagnosis of DVT and that measurement of both D-dimer and SF increases the sensitivity and specificity for the diagnosis of DVT/PE.

Clinical Usefulness of D-Dimer Depending on Clinical Probability and Cutoff Value in Outpatients With Suspected Pulmonary Embolism

We evaluated whether a highly sensitive D-dimer test is clinically useful and safe for ruling out pulmonary embolism (PE) in patients with a high clinical probability and whether adopting different cutoff values according to the clinical probability category might increase the proportion of patients in whom PE is ruled out. We retrospectively analyzed the databases of 2 outcome studies on the diagnosis of PE with a 3-month follow-up that included 1409 patients. We evaluated the usefulness of D-dimer testing by calculating the number needed to test to rule out one PE, and its safety by measuring the 3-month thromboembolic risk in patients not treated by anticoagulant agents based on a normal D-dimer level. The sensitivity of D-dimer was 100% in all clinical probability categories, but the number needed to test increased with increasing clinical probability of PE. The 95% confidence interval (0%-23%) of the 3-month thromboembolic risk (0%) among 13 of 121 patients with a normal D-dimer level and a high clinical probability of PE was wide. Increasing the cutoff value to 700 mug/L in patients with a low clinical probability would rule out PE in an additional 5% of the entire patient cohort at the expense of a lower sensitivity (93% [95% confidence interval, 83%-97%]). The safety of D-dimer testing in patients with a high clinical probability of PE is not established, and testing results are rarely negative in such patients. Increasing the enzyme-linked immunosorbent assay D-dimer cutoff value only marginally increased the test's usefulness.

Elevated plasma levels of fibrin degradation products by granulocyte-derived elastase in patients with deep vein thrombosis

Plasma levels of granulocyte-derived elastase (GE-XDP), D-dimer and soluble fibrin (SF) were examined in 53 patients with deep vein thrombosis (DVT) and in 100 healthy volunteers. The mean plasma level of D-dimer was 0.92±0.81 μg/ml (±S.D.) in healthy volunteers and the mean+2 S.D. value (cutoff value for DVT) was 2.53 μg/ml, which was higher than that used in Europe and North America. Plasma levels of GE-XDP, D-dimer and SF were significantly higher in patients with DVT than in healthy volunteers, and diminished after 1 week of treatment with heparin, urokinase or tissue type plasminogen activator, though were still higher than those of the control subjects. The sensitivity of GE-XDP, D-dimer and SF for DVT was 81.1%, 75.5% and 79.2%, respectively. GE-XDP levels correlated with those of D-dimer and SF. Our results indicate that GE-XDP is a potentially useful marker for the diagnosis of DVT, suggesting that granulocytes are activated in patients with DVT. In our system, the cutoff value of D-dimer for the diagnosis of DVT is higher than in western countries, probably due to the use of different analytical assays.

Extensive evaluation of the instrumentation laboratory IL test D-Dimer immunoturbidimetric assay on the ACL 9000 determines the D-Dimer cutoff value for reliable exclusion of venous thromboembolism.

The clinical diagnosis of venous thromboembolism (VTE), which includes both deep vein thrombosis (DVT) and pulmonary embolism (PE), is often difficult and requires a number of imaging tests plus clinical assessment. It is now accepted that pretest clinical probability of disease plus a sensitive, quantitative D-Dimer assay can be used to reliably exclude VTE. In design of diagnostic strategies for VTE it is recommended that the D-Dimer assay be evaluated for sensitivity and specificity in well-designed, blinded studies using a cohort of patients for whom the assay will ultimately be used. Therefore we evaluated the IL Test D-Dimer on the ACL 9000 automated coagulation analyzer for its sensitivity and specificity in the diagnosis of VTE. A total of 512 patients admitted to the emergency department of Providence Hospital with suspected VTE were included in the dataset. Our aim was to find the clinically meaningful IL Test D-Dimer cutoff value, which would give us 100% sensitivity and the highest possible specificity for exclusion of VTE. Patients were categorized clinically into low, medium, or high pretest probability and had computed tomographic and/or ventilation-perfusion scans for investigation of PE and ultrasound studies for suspected DVT, with the laboratory blinded to the clinical findings. Of the 511 patients, 28 (5.4%) had confirmed VTE (PE and/or DVT) based on imaging and clinical studies. Applying receiver operating characteristic curve (ROC) analysis, we determined from our study that a cutoff value of 237 ng/mL IL Test D-Dimer gave a 100% sensitivity with a specificity of 38% for detection of VTE. The findings demonstrate that a diagnostic strategy using the IL Test D-Dimer assay as a first-line test in combination with pretest probability is safe and can be used in patients with suspected VTE. In conclusion, patient analysis results indicating low or moderate pretest probability for VTE and a negative IL Test D-Dimer (cutoff value of 237 ng/mL) assay result on the ACL 9000 reliably exclude VTE (both PE and DVT). We expect that inclusion of the rapid IL Test D-Dimer assay for assessment of suspected VTE in the emergency department at Providence will result in improved patient diagnosis and therapy, reduction in unnecessary radiological investigations, and lowering of overall costs associated with investigation of patients suspected of having VTE disease.

Should the D-dimer Cut-off Value Be Increased in Elderly Patients Suspected of Pulmonary Embolism?

Should the D-dimer Cut-off Value Be Increased in Elderly Patients Suspected of Pulmonary Embolism? -