Our findings are consistent with published research showing that D-dimer levels increase with age. The new age-adjusted D-dimer cutoff value (age*0.02 mg/L) significantly improved the specificity of the D-dimer assay, from 22.2–61.3% (P < 0.05), and reduced the number needed to test to find one normal D-dimer test result to 1.5. When the new threshold was used, the proportion of patients in whom DVT could be safely ruled out among the six 5-year-apart age groups was between 52.0% and 59.7%, increasing by 66% when compared to the typical cutoff value of age*0.01 mg/L.
In the setting of both advanced age and a major trauma, the risk of DVT was higher than general population or other conditions, and investigation of targeted prompt examination method remains a key topic [27–30]. Other scholars tried to use adjustment formulas or other specific thresholds of well-established biomarkers to more accurately diagnose or predict the VTE after fracture. For example, Niikura et al  established D-dimer cutoff levels for VTE screening in patients with fractures caused by high-energy injuries and showed moderate or high accuracy (area under curve 0.7-1.0) for predicting a VTE;Wu et al  used the typical age-adjusted D-dimer cutoff value (age*0.01 mg/L) in patients with knee fracture or hip fracture, and the results showed it had a better value in predicting DVT than a traditional threshold. In this study, we have got a new coefficient related to age (0.02), demonstrating a significantly improved specificity in diagnosis of a DVT, aiding in safely excluding those without a DVT in a larger proportion.
Compared with previous thresholds, the new age-adjusted D-dimer cutoff value had higher specificity of 61.3%, significantly higher than 36.9% when using the typical age-adjusted D-dimer cutoff value. 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 definition, the reduction in sensitivity was due to the raising of the threshold for higher specificity, which caused some patients to fall below the new threshold and causes them to change from true positive to false negative.
Elderly patients with hip fractures can benefit from this new age-adjusted D-dimer value. A research on cost-effectiveness showed that the cost-effectiveness of applying traditional thresholds in older people over 80 was poor due to excessive DUS. The efficiency of typical age-adjusted D-dimer value was limited, in our study, the typical threshold only increases the specificity from 22.2% (0.05mg/L) to 36.9% while the specificity was 61.3% when the new age-adjusted cutoff value was used. The new age-adjusted D-dimer value increased the DVT excluded proportion of older hip fracture patients to 59.22%, comparing with 21.53% when the age-adjusted cutoff value (age*0.01 mg/L) was used. The increased specificity of the D-dimer test and DVT excluded proportion reduced the number of patients who need further DUS and unnecessary anticoagulant therapy with consequent clinical. The potential benefit would be fewer long waits and frequent mobility, thus decreasing physical impairments.
D-dimer test must be integrated with clinical pre-test probability (PTP) scores (such as the Wells score or the revised Geneva score) and DUS, when it was used to diagnosis DVT in published studies . But when using the new age-adjusted threshold, we believe that there is no need to consider PTP, because PTP is routinely used to screen the patients with low and moderate pretest probability[25, 33], elderly hip fracture patients usually have a moderate, or high pretest probability due to trauma, mobility limitations or other comorbidities. Moreover, the applicant effect of PTP is not good in clinical practice, and the rate of PTP in which clinicians’ adherence to standardized diagnostic procedures is as poor as 50–60% in prior studies [34, 35]. Simplified clinical assessment algorithms using the new age-adjusted formula and DUS can save time and energy for medical staff. The new age-adjusted D-dimer cutoff value should be applied to specific D-dimer assays. The wide diversities of D-dimer assays used in the published studies showed the difficulty selecting unified 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.