The diagnostic performance of APC–PCI complex determination compared to d-dimer in the diagnosis of deep vein thrombosis

d-dimer testing is widely used as part of the diagnostic algorithm for the exclusion of deep vein thrombosis (DVT) but is considered of limited in value for ruling DVT in. Since d-dimers are poorly defined, there is no standardization of the assays and this makes reliable comparisons between clinical studies difficult. We report on a performance evaluation of a new marker of activated coagulation (Activated Protein-C in complex with Protein-C inhibitor, APC–PCI complex) compared to two quantitative d-dimer assays (Vidas®d-dimer Exclusion™and Autodimer®). The post-hoc comparison was made on 350 frozen plasma samples from consecutive outpatients suspected of DVT in a multicenter management study including clinical probability score, d-dimer testing, venous ultrasound and contrast venography as part of the diagnostic algorithm. Results: The APC–PCI complex performed inferior to the d-dimer assays in terms of sensitivity: 74 vs. >93%, negative predictive value: 91 vs. >96% and area under the curve: 0.82 vs. 0.9, but showed a significantly higher specificity: 80 vs. 40–60%. Specificity for the APC–PCI complex did not decrease with higher clinical probability score and the positive predictive value was significantly higher than that of the d-dimer assays in the intermediate/high probability cohort (66 vs. <52%). In this probability cohort, high levels of the APC–PCI complex and to a lesser extent, d-dimers, can give positive predictive values of >90% in up to 20% of the patients which indicates important clinical implications. However, for the exclusion of DVT at the pre-specified cut-off level, the APC–PCI complex perform inferior to the d-dimer assays in this study.