Lisette van Dam

Wells rule and D-dimer test in recurrent ipsilateral DVT 4 69 DISCUSSION In this predefined analysis of the Theia study, we demonstrated that the combination of an unlikely CDR with a normal D-dimer test yielded a sensitivity of 97% (95%CI 92-99%) and a specificity of 36% (95%CI 28-45%) for recurrent ipsilateral DVT. Even though the predefined threshold for ‘adequate’ sensitivity was met, a failure rate of 6.1% (95%CI 1.3-18%) was observed. Our results are in line with a patient-level meta-analysis, in which it was concluded that an unlikely CDR by the original Wells rule combined with a normal D-dimer was not safe for excluding recurrent DVT (failure rate of 2.5%; 95%CI 1.2%-5.4%) in 941 patients with a history of DVT. 12 The modified Wells rule was created to improve the diagnostic performance of the original Wells rule. 12 However, applying themodifiedWells rule to our cohort lead to an even higher failure rate of 11% (95%CI 2.2-31%), mainly because fewer patients were categorized as having an unlikely CDR. These results are in contrast with the above-mentioned meta-analysis, in which the modified Wells rule was associated with an adequately low failure rate of 1.0% (95%CI 0.6-1.6%). 12 Importantly, the lower 24% recurrent DVT prevalence in this meta-analysis 12 needs to be taken into account when comparing the results with our study (prevalence of 45%). As the failure rate is dependent on the disease prevalence in a population or cohort, the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis (ISTH) has suggested a DVT prevalence-dependent diagnostic safety threshold. 15,16 The estimated sensitivity of the modified Wells rule in combination with D-dimer testing in the aforementioned meta-analysis was 99% 12 , compared to a sensitivity of 97% in our study cohort. Therefore, our study results are in line with previous literature and places this sensitivity in the context of a large cohort consisting exclusively of patients with suspected recurrent ipsilateral DVT. It must also be taken into account that for the estimation of the failure rate of an unlikely CDR in combination with a normal D-dimer test, we calculated the incidence of recurrent DVT at baseline and that of recurrent VTE during 3 months of follow-up after a MRDTI negative for DVT. Although it is possible that a recurrent DVT during follow-up was provoked by a newly emerged risk factor (e.g. immobilization or surgery), the chosen reference standard was in accordance with current guidelines in which it is stated that the standard against which all DVT