There is a clear clinical need for high specificity plasma biomarkers for predicting risk of venous thromboembolism (VTE), but thus far such markers have remained elusive. Utilising affinity reagents from the human protein atlas (HPA) project and multiplexed immuoassays we extensively analysed plasma samples from two individual cohorts to identify candidate protein markers associated with VTE risk. We screened plasma samples from 88 VTE cases and 85 matched controls, collected as part of the Swedish 'Venous Thromboembolism Biomarker Study' (VEBIOS), using suspension bead arrays composed of 755 antibodies targeting 408 candidate proteins. We identified significant associations between VTE occurrence and plasma levels of HIVEP1, VWF, GPX3 and PDGFB. For replication we profiled plasma samples of 580 cases and 589 controls from the French FARIVE study. This confirmed the association of VWF and PDGFB with VTE after correction for multiple testing, whilst only weak trends were observed for HIVEP1 and GPX3. Whilst plasma levels of VWF and PDGFB correlated modestly (ρ ~0.30) with each other, they were independently associated with VTE risk in a joint model in FARIVE (VWF p < 0.001; PDGFB p = 0.002). PDGFB was verified as the target of the capture antibody by immunocapture mass spectrometry (IC-MS) and sandwich ELISA. In conclusion, we demonstrate that high-throughput affinity plasma proteomic profiling is a valuable research strategy to identify potential candidate biomarkers for thrombosis related disorders, and our study suggests a novel association of PDGFB plasma levels with VTE.
