Performance of C-Reactive Protein, Procalcitonin, TAT Complex, and Factor VIII in Addition to D-Dimer in the Exclusion of Venous Thromboembolism in Primary Care Patients

Abstract

Background In primary care, D-dimer—combined with a clinical assessment—is recommended for ruling-out venous thromboembolism (VTE). However, D-dimer testing frequently yields false-positive results, notably in the elderly, and the search for novel biomarkers thus continues. We assessed the added diagnostic value of 4 promising laboratory tests. Methods Plasma samples from 256 primary care patients suspected of VTE were collected. We explored added value (beyond D-dimer) of C-reactive protein (CRP), procalcitonin (PCT), thrombin–antithrombin III complex (TAT-c), and factor VIII (FVIII). Diagnostic performance of these biomarkers was assessed univariably and by estimating their area under the receiver operating curve (AUC). Added diagnostic potential beyond D-dimer testing was assessed using multivariable logistic regression. Results Plasma samples of 237 VTE-suspected patients were available for analysis—36 patients (25%) confirmed deep vein thrombosis, 11 patients (12%) pulmonary embolism. Apart from D-dimer, only CRP, and FVIII levels appeared to be higher in patients with VTE compared to patients without VTE. The AUCs for these 3 markers were 0.76 (95% CI: 0.69–0.84) and 0.75 (95% CI: 0.68–0.83), respectively, whereas the AUC for D-dimer was 0.90 (95% CI: 0.86–0.94). Combining these biomarkers in a multivariable logistic model with D-dimer did not improve these AUCs meaningfully. Conclusions In our dataset, we were unable to demonstrate any added diagnostic performance beyond D-dimer testing of novel biomarkers in patients suspected of VTE in primary care. As such, D-dimer testing appears to remain the best choice in the exclusion of clinically suspected VTE in this setting. Trial Registration Netherlands Trial Register NL5974. (METC protocol number: 16-356/M; NL56475.041.16.)

Contemporary Biomarkers in Pulmonary Embolism Diagnosis: Moving beyond D-Dimers

“…The risk was not affected after adjustment for other possible risk factors [ 27 ]. Heerink et al found that the levels of FVIII were higher in patients with PE when compared with healthy controls, but the population of PE patients in this study was small ( n = 11) [ 33 ]. In contrast to the previous results pointing to the specificity of FVIII levels, Kamphuisen et al found high FVIII levels (≥150 IU/dL) at the acute phase in both PE patients and subjects with various etiologic substrates (pneumonia, heart failure, or malignancy) [ 25 ].…”