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

Senior, Kevin; Burles, K.; Wang, Dongmei; Grigat, D.; Innes, Grant; Andruchow, J.; Lang, Eddy; McRae, Andrew

doi:10.1017/cem.2018.389

Cited by 14 publications

(14 citation statements)

References 19 publications

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“…40 All these diagnostic strategies were found to perform better than the conventional strategy. The diagnostic strategy based on an agespecific cut-off level calculated by multiplying the patient's age by 10 after 50 years, which has become widely used in clinical wards, 37 has been evaluated in various populations using different reagents (e.g., Schouten et al, 39,[47][48][49][50][51][52][53][54][55] ), but few data were available for the HemosIL D-dimer HS 500 assay. This strategy was found associated with an increased test specificity, without any significant decreased sensitivity and NPV.…”

Section: Discussionmentioning

confidence: 99%

Age‐adjusted D‐dimer cut‐off levels to rule out venous thromboembolism in patients with non‐high pre‐test probability: Clinical performance and cost‐effectiveness analysis

Pooter

Brionne-François

Smahi³

et al. 2021

Journal of Thrombosis and Haemostasis

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Background: As aging was found to be associated with increased D-dimer levels, the question arose whether D-dimer measurement was useful in the diagnostic strategy of venous thromboembolism (VTE) in elderly patients. Aim of the study:To compare retrospectively the performance of six diagnostic strategies based on the three-level Wells scores and various cut-off levels for D-dimer, evaluated using the HemosIL D-Dimer HS 500 assay, in a derivation cohort of 644 outpatients with non-high pretest probability (PTP) of VTE. The clinical usefulness of the best-performing strategy was then confirmed in a multicenter validation study involving 1255 consecutive outpatients with non-high PTP. Results:The diagnostic strategy based on the age-adjusted cut-off level calculated by multiplying the patient's age by 10 above 50 years was found to perform the best in the derivation study with a better sensitivity-to-specificity ratio than the conventional strategy based on the fixed cut-off level (500 ng/ml), a higher specificity and a negative predictive value (NPV) above 99%. Such an increase in test specificity was confirmed in the validation cohort, with the NPV remaining above 99%. Taking into account the local reimbursement rates of diagnostic tests, using this strategy led to a 6.9% reduction of diagnostic costs for pulmonary embolism and a 5.1% reduction for deep vein thrombosis, as imaging tests would be avoided in a higher percentage of patients. Conclusion:The diagnostic strategy of VTE based on the age-adjusted cut-off level for D-dimer in patients over 50 years was found to be safe, with NPV above 99%, and cost-effective.

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Section: Discussionmentioning

confidence: 99%

Age‐adjusted D‐dimer cut‐off levels to rule out venous thromboembolism in patients with non‐high pre‐test probability: Clinical performance and cost‐effectiveness analysis

Pooter

Brionne-François

Smahi³

et al. 2021

Journal of Thrombosis and Haemostasis

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“…The number of patients with a negative D-dimer result increases from 594 (22%) when the traditional threshold of 0.5 mg/L is used to 1293 (59%) when the new age-adjusted formula is used. By definition, the reduction in sensitivity is due to the raising of the threshold for higher specificity, which causes some patients to fall below the new threshold and causes them to change from true positive to false negative [ 35 ].…”

Section: Discussionmentioning

confidence: 99%

Role of a new age-adjusted D-dimer cutoff value for preoperative deep venous thrombosis exclusion in elderly patients with hip fractures

et al. 2021

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Objective This study aimed to describe the characteristics of plasma D-dimer level with increasing age and establish a new age-adjusted D-dimer cutoff value for excluding preoperative lower limb deep vein thrombosis (DVT) in elderly patients with hip fractures. Methods This was a retrospective study of elderly patients who presented with acute hip fracture in our institution between June 2016 and June 2019. All patients underwent D-dimer test and duplex ultrasound. Patients were divided into six 5-year-apart age groups. The optimal cutoff value for each group was calculated by using receiver operating characteristic (ROC) curves, whereby the new age-adjusted D-dimer cutoff value was determined. The sensitivity, specificity, positive predictive values (PPV) and negative predictive values (NPV) were calculated and compared when different D-dimer cutoff values were applied, i.e., conventional 0.5 mg/L, previously well-established age-adjusted cutoff value (age × 0.01 mg/L) and the new age-adjusted D-dimer cutoff value herein. Results There were 2759 patients included, 887 males and 1872 females, with an average age of 78 years. In total, 280 patients were diagnosed with preoperative DVT. The optimal cutoff values for the six age groups were 0.715 mg/L, 1.17 mg/L, 1.62 mg/L, 1.665 mg/L, 1.69 mg/L and 1.985 mg/L, respectively, and the calculated age-adjusted coefficient was 0.02 mg/L. With this new coefficient applied, the specificity was 61%, clearly higher than those for conventional threshold (0.5 mg/L, 37%) or previously established age-adjusted D-dimer threshold (age × 0.01 mg/L, 22%). In contrast, the sensitivity was lower than that (59% vs 85% or 77%) when D-dimer threshold of 0.5 mg/L or age-adjusted cutoff value (age × 0.01 mg/L) was used. The other indexes as PPV (15%, 11% and 12%) and NPV (93%, 93% and 94%) were comparable when three different D-dimer thresholds were applied. Conclusions We developed a new age-adjusted D-dimer cutoff value (age × 0.02 mg/L) for a specified high-risk population of patients aged 65 years or older with hip fractures, and demonstrated the improved utility of the D-dimer test for exclusion of DVT. This formula can be considered for use in elderly hip fracture patients who meet the applicable standards as preoperative DVT screening, after its validity is confirmed by more well-evidenced studies.

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“…The number of patients with a negative D-dimer result increased from 594 (21.53%) when the traditional threshold of 0.5 mg/L was used to 1293 (59.22%) when the new age-adjusted formula was used. By de nition, the reduction in sensitivity was due to the raising of the threshold for higher speci city, which caused some patients to fall below the new threshold and causes them to change from true positive to false negative [31].…”

Section: Discussionmentioning

confidence: 99%

“…The new age-adjusted D-dimer cutoff value should be applied to speci c Ddimer assays. The wide diversities of D-dimer assays used in the published studies showed the di culty selecting uni ed reference ranges and clinical thresholds, because of the multiple combinations of monoclonal antibodies and different assay reagent,and diverse D-dimer assays had the substantial differences in analytical performance [31,36,37]. The age-adjustment formula should be established based on different D-dimer assays correspondingly, instead of being widely used without a second thought.…”

Section: Discussionmentioning

confidence: 99%

Role of a New Age-adjusted D-dimer Cutoff Value for Preoperative Deep Venous Thrombosis Exclusion in Elderly Patients With Hip Fractures

Zhang

Zhu

Tian

et al. 2021

Preprint

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Objective: This study aimed to describe the characteristics of plasma D-dimer level with increasing age and establish a new age-adjusted D-dimer cutoff value for excluding preoperative lower limb deep vein thrombosis (DVT) in elderly patients with hip fractures.Methods: This was a retrospective study of elderly patients who presented with acute hip fracture in our institution between June 2014 and May 2020. All patients underwent D-dimer test and duplex ultrasound. Patients were divided into six 5-year-apart age groups. The optimal cutoff value for each group was calculated by using receiver operating characteristic (ROC) curves, whereby the new age-adjusted D-dimer cutoff value was determined. The sensitivity, specificity, positive predictive values (PPV) and negative predictive values (NPV) were calculated and compared when different D-dimer cutoff values were applied, i.e. conventional 0.5mg/L, previously well-established age-adjusted cutoff value (age*0.01 mg/L) and the new age-adjusted D-dimer cutoff value herein. Results: There were 2759 included, 887 males and 1872 females, with an average age of 77.8 years. 280 patients were diagnosed with preoperative DVT. The optimal cutoff values for the six age groups were 0.715 mg/L, 1.170 mg/L, 1.620 mg/L, 1.665 mg/L, 1.690 mg/L and 1.985 mg/L, respectively and the calculated age-adjusted coefficient was 0.02 mg/L. With this new coefficient applied, the specificity was 61.3%, clearly higher than those for conventional threshold (0.5mg/L, 36.9%) or previously established age-adjusted D-dimer threshold (age*0.01 mg/L, 22.2%). In contrast, the sensitivity was lower than that (58.9% vs 85.0% or 77.1%) when D-dimer threshold of 0.5 mg/L or age-adjusted cutoff value (age*0.01 mg/L) was used. The other indexes as PPV (14.7%, 11.0% and 12.1%) and NPV (93.0%, 92.9% and 93.5%) were comparable when three different D-dimer thresholds were applied. Conclusions: The use of the new age-adjusted D-dimer threshold increased the proportion of elderly hip fracture patients in whom preoperative lower limb deep vein thrombosis could be safely excluded.

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

Cited by 14 publications

References 19 publications

Age‐adjusted D‐dimer cut‐off levels to rule out venous thromboembolism in patients with non‐high pre‐test probability: Clinical performance and cost‐effectiveness analysis

Age‐adjusted D‐dimer cut‐off levels to rule out venous thromboembolism in patients with non‐high pre‐test probability: Clinical performance and cost‐effectiveness analysis

Role of a new age-adjusted D-dimer cutoff value for preoperative deep venous thrombosis exclusion in elderly patients with hip fractures

Role of a New Age-adjusted D-dimer Cutoff Value for Preoperative Deep Venous Thrombosis Exclusion in Elderly Patients With Hip Fractures

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