Age-Adjusted D-Dimer Cutoffs for DVT and Pulmonary Embolism: A Comparison of Five Assays

Abstract Background: Venous thromboembolism (VTE) is a common but underdiagnosed condition constituted primarily by deep venous thrombosis (DVT, 2/3) and pulmonary embolism (PE, 1/3).Diagnosis of VTE is based on the biomarker D-dimer for excluding low probability VTE, and imaging techniques to verify mid/high probability VTE. D-dimer assays generally have excellent sensitivity, but specificity is kept low by the physiology of the measurand. The plasma concentration of D-dimer increases in thrombosis and activated coagulation, but also in several other conditions such as pregnancy, cancer, trauma, inflammation, infection and with age. Many of these conditions are especially prevalent in VTE-patients, because they are also linked to an increased risk of venous thrombosis. Haase et al. showed that the plasma concentration of D-dimer in a healthy population increases with age, 50% of those ≥70 years old had a positive D-dimer (>0.5 mg/L FEU)1. Age-adjusted decision thresholds have subsequentially been recommended and validated, to increase specificity and reduce the rate of false positive D-dimer results in older patients without decreasing sensitivity. Aims: The study compares age-adjusted D-dimer decision thresholds for different assays in Swedish out-patients with suspected DVT or PE. Methods: Patients (n=940) with clinically suspected PE or DVT in a lower limb were recruited from the medical emergency department (ED) of Karolinska University Hospital, and fresh citrated plasma samples were analyzed for D-dimer within 30 minutes. D-dimer concentrations were measured by four immunoturbidimetric assays using the instruments Sysmex CS2100i and Stago CompactMax. VTE was verified by imaging techniques (ultrasonography, computed tomography or ventilation/perfusion lung scintigraphy, as appropriate) and classified into segmental or subsegmental PE and proximal or distal DVT. Non-VTE was identified by imaging techniques or absence of VTE in a three month follow up of medical records. Age adjusted cutoff values were calculated if age was ≥50 years according to Douma et al.2, as age x 0.01 for assays measured in mg/L FEU (Siemens INNOVANCE® D-dimer and STA®-Liatest® D-Di) and as age x 0.005 for Roche Tina-quant D-dimer and as age x 0.004 for MediRox D-dimer. Results: VTE was found in 125 patients (13.3%), PE in 35 (3.7%; 3.0% segmental and 0.7% subsegmental) and DVT in 90 (9.6%; 6.3% proximal and 3.4% distal). The diagnostic performances of the assays are displayed below, see table 1. All assays had excellent areas under the ROC-curve (AUC) and all except MediRox D-dimer fulfilled the FDA requirements of sensitivity > 95% and a NPV > 97%, at the cutoff recommended by the manufacturer. When age adjusted cutoffs were applied, all assays maintained their sensitivities, whereas specificities increased by 6-7%. The rate of false positive results decreased by 6% overall, but 10-20% for patients older than 70, see table 2. Conclusion: D-dimer is still the only biomarker used for suspected VTE, even though low specificity with false positive results presents a significant problem due to an elderly patient population burdened with co-morbidity. The examined age-adjusteddecision thresholds increase specificity for VTE without decreasing sensitivity and can thus be used to improve diagnosis of VTE. With fewer false positives, diagnosis will be faster, cheaper and will result in decreased health risks from intravenous contrast, radiation and unnecessary hospital admissions. References 1. Haase C, et al. Age- and sex-dependent reference intervals for D-dimer: evidence for a marked increase by age. Thromb Res. 2013;132(6):676-80. 2. Douma RA, et al. Potential of an age adjusted D-dimer cut-off value to improve the exclusion of pulmonary embolism in older patients: a retrospective analysis of three large cohorts. BMJ. 2010;340:c1475. Disclosures Farm: Leo Pharma: Research Funding; Triolab: Honoraria; Siemens: Honoraria. Chaireti:Baxalta: Research Funding. Antovic:Siemens: Honoraria; Roche: Honoraria; Baxter Healthcare Corporation: Honoraria, Research Funding; Novo Nordisk: Honoraria; Sysmex: Honoraria; Stago: Honoraria.

Download Full-text

Age-adjusted D-dimer thresholds in the investigation of suspected pulmonary embolism: A retrospective evaluation in patients ages 50 and older using administrative data

CJEM ◽

10.1017/cem.2018.389 ◽

2018 ◽

Vol 20 (5) ◽

pp. 725-731 ◽

Cited By ~ 1

Author(s):

Kevin Senior ◽

Kristin Burles ◽

Dongmei Wang ◽

Daniel Grigat ◽

Grant D. Innes ◽

...

Keyword(s):

Pulmonary Embolism ◽

Clinical Practice ◽

Administrative Data ◽

Older Patients ◽

Reference Value ◽

Actual Clinical Practice ◽

Patients Âgés ◽

Test Characteristics ◽

Increased Risk ◽

D Dimer

AbstractObjectivesD-dimer testing is an important component of the workup for pulmonary embolism (PE). However, age-related increases in D-dimer concentrations result in false positives in older adults, leading to potentially unnecessary imaging utilization. The objective of this study was to quantify the test characteristics of an age-adjusted D-dimer cut-off for ruling out PE in older patients investigated in actual clinical practice.MethodsThis observational study used administrative data from four emergency departments from July 2013 to January 2015. Eligible patients were ages 50 and older with symptoms of PE who underwent D-dimer testing. The primary outcome was 30-day diagnosis of PE, confirmed by imaging reports. Test characteristics of the D-dimer assay were calculated using the standard reference value (500 ng/ml), the local reference value (470 ng/ml), and an age-adjusted threshold (10 ng/ml × patient’s age).ResultsThis cohort includes 6,655 patients ages 50 and older undergoing D-dimer testing for a possible PE. Of these, 246 (3.7%) were diagnosed with PE. Age-adjusted D-dimer cut-offs were more specific than standard cut-offs (75.4% v. 63.8%) but less sensitive (90.3% v. 97.2%). The false-negative risk in this population was 0.49% using age-adjusted D-dimer cut-offs compared with 0.15% with traditional cut-offs.ConclusionAge-adjusted D-dimer cut-offs are substantially more specific than traditional cut-offs and may reduce CT utilization among older patients with suspected PE. We observed a loss of sensitivity, with an increased risk of false-negatives, using age-adjusted cut-offs. We encourage further evaluation of the safety and accuracy of age-adjusted D-dimer cut-offs in actual clinical practice.

Download Full-text

Improving the Efficacy of Non-Radiologic Exclusion of Deep Venous Thrombosis in the Elderly Using the Thrombin Generation Assay

Blood ◽

10.1182/blood.v112.11.3815.3815 ◽

2008 ◽

Vol 112 (11) ◽

pp. 3815-3815

Author(s):

Fred JLM Haas ◽

Roger EG Schutgens ◽

Douwe Biesma

Keyword(s):

Venous Thrombosis ◽

Deep Venous Thrombosis ◽

Predictive Value ◽

False Positive ◽

Thrombin Generation ◽

The Elderly ◽

Thrombin Generation Assay ◽

Additional Value ◽

Positive Results ◽

D Dimer

Abstract Background: Exclusion of deep venous thrombosis (DVT) using a pretest probability score (PTP) and a normal D-dimer concentration has proven to be safe and feasible. However, the high frequency of false positive D-dimer results in the elderly hampers its use, necessitating additional compression ultrasound (CUS) in these patients. We evaluated an alternative approach for the exclusion of DVT, especially in the elderly, using a thrombin generation assay (TGA) in combination with a PTP and a D-dimer assay. Patients and methods: In symptomatic outpatients suspected for DVT, the Endogenous Thrombin Potential (ETP) assay (Dade Behring Marburg GmBH, a Siemens Company, Germany) was tested. The results of this assay were expressed as ETP % NV (normalized value) [%], ETP AUC (area under the curve) [mE], ETP tlag (lagtime) [sec], ETP tmax (time to peak) [sec] and ETP Cmax (peak value) [mE/sec]. In all patients, a Tina-Quant D-dimer assay (Roche, Manheim, Germany) and a PTP according to Wells were performed. DVT was diagnosed or excluded using B-mode CUS. Results: A total of 443 patients were included (38% men, mean age 60 y). Total DVT prevalence was 39%. In the total group, the Tina-Quant D-dimer assay had a sensitivity (sens) of 98.9%, a negative predictive value (NPV) of 98.3% and a specificity (spec) of 41.9%. Combining D-dimer with a PTP < 2, these values were 100%, 100% and 52.2% respectively. With a spec of 51.8%, a large number of false positive results remain. All ETP parameters had a low AUC of the receiver operation curve (ROC), range 0.53–0.64. For all ETP parameters, there was a significant difference (p < 0.001) between patients with and without DVT, except ETP tmax. ETP parameters were tested for additional value to Tina-Quant and PTP. Only ETP tlag demonstrated an additional value, using an optimal cut-off value of 23.0 sec. In patients with a low PTP and an abnormal D-dimer value, that might be false positive, adding ETP tlag improved specificity to 87.5%, but sensitivity decreased to 26.5%. The percentage false positive results decreased from 38 to 8%, with an increase of false negative results. However, in the fourth age quartile cohort (patients >75 y), sensitivity reached 100% with a specificity of 94.1% and a decrease of false positive results from 58 to 5% (Table). Discussion and conclusion: In this study, a safe exclusion of DVT is possible with a low PTP and a normal D-dimer result as first step. Combining ETP tlag with a low PTP and an abnormal Tina-Quant D-dimer as second step (figure), the sens and NPV reached values of 100% in the fourth age quartile cohort. This algorithm should be confirmed by a new management study. Table. Performance of Tina-Quant (TQ) in relation to DVT, < 500 μg/l, low PTP + TQ < 500 μg/l and low PTP + TQ ≥ 500 μg/l + ETP tlag < 23.0 sec in the total cohort and the fourth age quartile; values (95% lower confidence limit) Sens Spec NPV false pos Sens = sensitivity, Spec = specificity, NPV = negative predictive value and false pos = false positive Total Tina-Quant < 500 98.9 (96.1) 41.9 (36.2) 98.3 (94.2) 35.4 PTP + TQ < 500 100 (92.6) 51.8 (43.8) 100 (94.9) 37.7 PTP + TQ > 500 + tlag 26.5 (12.9) 87.5 (76.8) 69.1 (57.9) 8.1 Elderly Tina-Quant < 500 100 (89.4) 23.9 (14.6) 100 (80.5) 51.9 PTP + TQ < 500 100 (15.8) 37.5 (18.8) 100 (66.4) 57.7 PTP + TQ > 500 + tlag 100 (15.8) 94.1 (65.3) 100 (84.6) 5.2 Figure. Algorithm for exclusion of DVT Figure. Algorithm for exclusion of DVT

Download Full-text

Evidence for Age-Adjusted D-Dimer to Rule out Pulmonary Embolism: An Institutional Study

American Journal of Clinical Pathology ◽

10.1093/ajcp/aqaa137.007 ◽

2020 ◽

Vol 154 (Supplement_1) ◽

pp. S5-S5

Author(s):

Ridin Balakrishnan ◽

Daniel Casa ◽

Morayma Reyes Gil

Keyword(s):

Pulmonary Embolism ◽

False Positive ◽

False Positive Rate ◽

Moderate Risk ◽

Older Population ◽

Statistical Measures ◽

Positive Rate ◽

Risk Patients ◽

D Dimer ◽

Rule Out

Abstract The diagnostic approach for ruling out suspected acute pulmonary embolism (PE) in the ED setting includes several tests: ultrasound, plasma d-dimer assays, ventilation-perfusion scans and computed tomography pulmonary angiography (CTPA). Importantly, a pretest probability scoring algorithm is highly recommended to triage high risk cases while also preventing unnecessary testing and harm to low/moderate risk patients. The d-dimer assay (both ELISA and immunoturbidometric) has been shown to be extremely sensitive to rule out PE in conjunction with clinical probability. In particularly, d-dimer testing is recommended for low/moderate risk patients, in whom a negative d-dimer essentially rules out PE sparing these patients from CTPA radiation exposure, longer hospital stay and anticoagulation. However, an unspecific increase in fibrin-degradation related products has been seen with increase in age, resulting in higher false positive rate in the older population. This study analyzed patient visits to the ED of a large academic institution for five years and looked at the relationship between d-dimer values, age and CTPA results to better understand the value of age-adjusted d-dimer cut-offs in ruling out PE in the older population. A total of 7660 ED visits had a CTPA done to rule out PE; out of which 1875 cases had a d-dimer done in conjunction with the CT and 5875 had only CTPA done. Out of the 1875 cases, 1591 had positive d-dimer results (>0.50 µg/ml (FEU)), of which 910 (57%) were from patients older than or equal to fifty years of age. In these older patients, 779 (86%) had a negative CT result. The following were the statistical measures of the d-dimer test before adjusting for age: sensitivity (98%), specificity (12%); negative predictive value (98%) and false positive rate (88%). After adjusting for age in people older than 50 years (d-dimer cut off = age/100), 138 patients eventually turned out to be d-dimer negative and every case but four had a CT result that was also negative for a PE. The four cases included two non-diagnostic results and two with subacute/chronic/subsegmental PE on imaging. None of these four patients were prescribed anticoagulation. The statistical measures of the d-dimer test after adjusting for age showed: sensitivity (96%), specificity (20%); negative predictive value (98%) and a decrease in the false positive rate (80%). Therefore, imaging could have been potentially avoided in 138/779 (18%) of the patients who were part of this older population and had eventual negative or not clinically significant findings on CTPA if age-adjusted d-dimers were used. This data very strongly advocates for the clinical usefulness of an age-adjusted cut-off of d-dimer to rule out PE.

Download Full-text

Abstract WP179: Rate of Pulmonary Embolism After Cerebral Venous Thrombosis

Stroke ◽

10.1161/str.48.suppl_1.wp179 ◽

2017 ◽

Vol 48 (suppl_1) ◽

Author(s):

Ava L Liberman ◽

Alexander E Merkler ◽

Gino Gialdini ◽

Michael P Lerario ◽

Steven R Messe ◽

...

Keyword(s):

Risk Factors ◽

Pulmonary Embolism ◽

Venous Thrombosis ◽

Vascular Risk Factors ◽

Emergency Department Visits ◽

Administrative Claims ◽

Cerebral Vein ◽

Vascular Risk ◽

Index Hospitalization ◽

Increased Risk

Introduction: Cerebral vein thrombosis (CVT) is associated with an increased risk of subsequent venous thromboembolism. It is unknown whether the risk of pulmonary embolism (PE) after CVT is similar to that of PE after deep venous thrombosis (DVT). Methods: We performed a retrospective cohort study using administrative claims data from all emergency department visits and hospitalizations in California from 2005-2011, New York from 2006-2013, and Florida from 2005-2013. We identified patients with CVT or DVT as well as the primary outcome of PE using previously validated International Classification of Diseases, Ninth Revision, Clinical Modification ( ICD-9-CM ) codes. In order to minimize misclassification error, patients with both CVT and DVT during the same index hospitalization were excluded and patients with CVT were censored at the time of development of DVT and vice versa. Kaplan-Meier survival statistics and Cox proportional hazards models were used to compare the risk of PE after CVT versus after DVT while adjusting for demographics, vascular risk factors, and the Elixhauser comorbidity index. Results: We identified 4,450 patients with CVT and 217,589 patients with DVT. During a mean follow-up of 2.0 (±1.7) years, 124 patients with DVT developed a PE and 18,698 patients with DVT developed a PE. Patients with CVT were younger (mean age 45 vs 63), more often female (71% vs 52%), more often pregnant, and had fewer vascular risk factors than patients with DVT. During the index hospitalization, the rate of PE was 1.5% (95% confidence interval [CI], 1.1-1.8%) in patients with CVT and 6.2% (95% CI, 6.1-6.3%, p<0.001) in patients with DVT. By 5 years, the cumulative rate of PE after CVT was 3.7% (95% CI, 3.0-4.4%) compared to 10.5% (95% CI, 10.3-10.6%, p<0.001) after DVT. After adjustment for demographics and comorbidities, CVT was associated with a significantly lower hazard of PE when compared to DVT (hazard ratio, 0.31; 95% CI, 0.26-0.38). Conclusion: In a large, heterogeneous population, we found that the risk of PE after CVT was significantly lower than that of PE after DVT. Among patients with CVT, the greatest risk for PE was apparent during the index hospitalization.

Download Full-text

THE ASSOCIATION BETWEEN D-DIMER AND DEEP VEIN THROMBOSIS LOCATION AND ITS ABILITY TO PREDICT PULMONARY EMBOLISM, a retrospective pilot study

10.21203/rs.2.11438/v1 ◽

2019 ◽

Author(s):

Sarah Ali Althomali ◽

Adel S. Alghamdi ◽

Tareef H. Gnoot ◽

Mohammad A. Alhassan ◽

Abdullatif H. Ajaimi ◽

...

Keyword(s):

Pulmonary Embolism ◽

Deep Vein Thrombosis ◽

Risk Group ◽

Great Role ◽

Vein Thrombosis ◽

Increased Risk ◽

Risk Patients ◽

Deep Vein ◽

Limb Deep Vein Thrombosis ◽

D Dimer

Abstract Background In lower limb deep vein thrombosis; it is important to identify proximal from distal deep vein thrombosis as it carries the highest risk of pulmonary embolism. It is known that D-dimer has a great role in deep vein thrombosis diagnosis. Yet, the use of D-dimer to predict the location of deep vein thrombosis and the risk of pulmonary embolism in deep vein thrombosis patients has not been investigated before. Objective To address the correlation between D-dimer and the location of deep vein thrombosis and to study the efficacy of D-dimer to predict risk of PE in patients with proximal or extensive deep vein thrombosis. Method We included 110 consecutive patients who were hospitalized with the diagnosis of deep vein thrombosis, with or without a concomitant diagnosis of PE, and with D-dimer measured at initial presentation. We categorized the location of deep vein thrombosis as: distal, proximal, and extensive. In the analysis, patients were grouped into high-risk (patients with Proximal or Extensive deep vein thrombosis and pulmonary embolism) and low risk group (patients without pulmonary embolism). Results There was no significant association between D-dimer level and the location of deep vein thrombosis (p=0.519). However, D-dimer level was greater among patients with pulmonary embolism (9.6mg/L) than among patients without pulmonary embolism (7.4mg/L), (p=0.027). D-dimer was a significant predictor of pulmonary embolism as patients with proximal or extensive deep vein thrombosis had 8-folds increased risk of pulmonary embolism than patients with D-dimer less than 4.75mg/L (OR=7.9, p=0.013). Conclusion Though D-dimer was not significantly associated with the location of deep vein thrombosis, it was a significant predictor of pulmonary embolism in patients hospitalized with proximal or extensive deep vein thrombosis.

Download Full-text

Venous Thromboembolism

10.2310/fm.1102 ◽

2020 ◽

Author(s):

Samuel Z. Goldhaber

Keyword(s):

Risk Factors ◽

Pulmonary Embolism ◽

Venous Thromboembolism ◽

Venous Thrombosis ◽

Antithrombotic Agents ◽

Vein Thrombosis ◽

Recurrent Venous Thrombosis ◽

Deep Vein ◽

D Dimer ◽

In Pregnancy

Venous thromboembolism, which involves venous thrombosis and pulmonary embolism, is a leading cause of morbidity and mortality in hospitalized patients and is being seen with increasing frequency in outpatients. This chapter discusses the risk factors, etiology, classification, pathophysiology, natural history, prognosis, diagnosis (including venous thrombosis, recurrent venous thrombosis, and pulmonary embolism), prophylaxis, and treatment of venous thromboembolism (including the pharmacology of antithrombotic agents), as well as venous thromboembolism in pregnancy and miscellaneous thromboembolic disorders (including thrombosis of unusual sites). This review contains 8 figures, 16 tables, and 79 references. Keywords: Venous thromboembolism, pulmonary embolism, deep vein thrombosis, embolectomy, thrombolysis, hypercoagulability, duplex ultrasonography, D-dimer, anticoagulation

Download Full-text

Epidemiology, morbidity and mortality in Behçet’s disease: a cohort study using The Health Improvement Network (THIN)

Rheumatology ◽

10.1093/rheumatology/keaa010 ◽

2020 ◽

Vol 59 (10) ◽

pp. 2785-2795 ◽

Cited By ~ 1

Author(s):

Tom Thomas ◽

Joht Singh Chandan ◽

Anuradhaa Subramanian ◽

Krishna Gokhale ◽

George Gkoutos ◽

...

Keyword(s):

Pulmonary Embolism ◽

Cohort Study ◽

Heart Disease ◽

General Population ◽

Venous Thrombosis ◽

Ischaemic Heart Disease ◽

Thromboembolic Disease ◽

Age And Gender ◽

Increased Risk ◽

And Gender

Abstract Objectives The epidemiology of Behçet’s disease (BD) has not been well characterized in the UK. Evidence on the risk of cardiovascular disease, thromboembolic disease and mortality in patients with BD compared with the general population is scarce. Methods We used a large UK primary care database to investigate the epidemiology of BD. A retrospective matched cohort study was used to assess the following outcomes: risk of cardiovascular, thromboembolic disease and mortality. Controls were selected at a 1:4 ratio (age and gender matched). Cox proportional hazard models were used to derive adjusted hazard ratios (aHR). Results The prevalence of BD was 14.61 (95% CI 13.35–15.88) per 100 000 population in 2017. A total of 1281 patients with BD were compared with 5124 age- and gender-matched controls. There was significantly increased risk of ischaemic heart disease [aHR 3.09 (1.28–7.44)], venous thrombosis [aHR 4.80 (2.42–9.54)] and mortality [aHR 1.40 (1.07–1.84)] in patients with BD compared with corresponding controls. Patients with BD were at higher risk of pulmonary embolism compared with corresponding controls at baseline [adjusted odds ratio 4.64 (2.66–8.09), P < 0.0001]. The majority of patients with pulmonary embolism and a diagnosis of BD had pulmonary embolism preceding the diagnosis of BD, not after (87.5%; n = 28/32). Conclusion BD has a higher prevalence than previously thought. Physicians should be aware of the increased risk of developing ischaemic heart disease, stroke/transient ischaemic attack and deep venous thrombosis in patients with BD at an earlier age compared with the general population. Risk of embolism in patients with BD might vary across the disease course.

Download Full-text

Ileus following total hip or knee arthroplasty is associated with increased risk of deep venous thrombosis and pulmonary embolism

The Journal of Arthroplasty ◽

10.1016/j.arth.2003.12.033 ◽

2004 ◽

Vol 19 (2) ◽

pp. 259

Author(s):

Keith R. Berend ◽

Adolph V. Lombardi ◽

Thomas H. Mallory ◽

Kathleen L. Dodds

Keyword(s):

Pulmonary Embolism ◽

Venous Thrombosis ◽

Deep Venous Thrombosis ◽

Knee Arthroplasty ◽

Total Hip ◽

Increased Risk

Download Full-text

LO06: Role of the age adjusted D-dimer in suspected deep venous thrombosis

CJEM ◽

10.1017/cem.2017.68 ◽

2017 ◽

Vol 19 (S1) ◽

pp. S29

Author(s):

P. Reardon ◽

S. Patrick ◽

M. Taljaard ◽

K. Thavorn ◽

M.A. Mukarram ◽

...

Keyword(s):

Diagnostic Accuracy ◽

Venous Thrombosis ◽

Deep Venous Thrombosis ◽

Older Patients ◽

Large Scale ◽

False Negative ◽

Cost Savings ◽

Low Risk ◽

Clinical Probability ◽

D Dimer

Introduction: It is well established that a negative D-dimer will reliably rule out thromboembolism in selected low risk patients. Multiple modified D-dimer cutoffs have been suggested for older patients to improve diagnostic specificity. However, these approaches are better established for pulmonary embolism than for deep venous thrombosis (DVT). This study will evaluate the diagnostic performance of previously suggested D-dimer cutoffs for low risk DVT patients in the ED, and assess for a novel cutoff with improved performance. Methods: This health records review included patients >50 years with suspected DVT who were low-risk and had a D-dimer performed. Our analysis evaluated the diagnostic accuracy of D-dimer cutoffs of 500 and the age adjusted (age x 10) rule for patients >50 years; and 750, and 1,000 cutoffs for patients >60 years. 30-day outcome was a diagnosis of DVT. We also assessed the diagnostic accuracy for a novel cutoff (age x 12.5). Results: 1,000 patients (mean age 68 years; 59% female) were included. Of these, 110 patients (11%) were diagnosed with DVT. The conventional cutoff of <500 µg/L demonstrated a sensitivity of 99.1% (95% CI 95.0-99.9) and a specificity of 36.4% (95% CI 33.2-39.7). For patients >60 years, the absolute cutoffs of 750 and 1,000 showed sensitivity of 98.7% (95% CI, 92.9, 99.9), and the specificity increased to 48.6% (95% CI, 44.5-52.8%) and 62.1% (95% CI, 58.1-66.1%) respectively. For all study patients, age adjusted D-dimer demonstrated a sensitivity of 99.1% (95% CI 95.0-99.9) and a specificity of 51.2% (95% CI, 47.9-54.6). A novel age adjusted cutoff (age x 12.5) for patients >50, demonstrated a sensitivity of 97.3% (95% CI 92.2-99.4) and a specificity of 61.2% (95% CI 58.0-64.5). When compared to conventional cutoff, the age adjusted cutoffs (age x 10 and age x 12.5) would have resulted in an absolute decrease in further investigations of 13.1% and 22.2%, respectively, with false negative rates of 0.1% and 0.3%. Conclusion: Among older patients with suspected DVT and low clinical probability, the age adjusted D-dimer increases the proportion of patients among whom DVT can be ruled out. A novel cutoff (age x 12.5) demonstrated improved specificity. Future large scale prospective studies are needed to confirm this finding and to explore the cost savings of these approaches.

Download Full-text