PDGFB, a new candidate plasma biomarker for venous thromboembolism: results from the VEREMA affinity proteomics study

Abstract

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. Utilizing affinity reagents from the Human Protein Atlas project and multiplexed immuoassays, we extensively analyzed plasma samples from 2 individual studies 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," using suspension bead arrays composed of 755 antibodies targeting 408 candidate proteins. We identified significant associations between VTE occurrence and plasma levels of human immunodeficiency virus type I enhancer binding protein 1 (HIVEP1), von Willebrand factor (VWF), glutathione peroxidase 3 (GPX3), and platelet-derived growth factor β (PDGFB). For replication, we profiled plasma samples of 580 cases and 589 controls from the French FARIVE study. These results confirmed the association of VWF and PDGFB with VTE after correction for multiple testing, whereas only weak trends were observed for HIVEP1 and GPX3. Although 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 < .001; PDGFB P = .002). PDGFΒ was verified as the target of the capture antibody by immunocapture mass spectrometry and sandwich enzyme-linked immunosorbent assay. 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.

Protein biomarkers for incident deep venous thrombosis in critically ill adolescents: An exploratory study

“…Despite the current focus on genomics, the proteome may be more useful than the genome in predicting DVT. DVT is a multifactorial condition, such that a single gene defect is unlikely to identify a large number of critically ill children at risk of DVT . Unlike genetic tests, tests to measure levels of proteins with quick turnaround times can readily be developed to allow for the timely initiation of pharmacologic thromboprophylaxis …”

“…DVT is a multifactorial condition, such that a single gene defect is unlikely to identify a large number of critically ill children at risk of DVT. 5,6 Unlike genetic tests, tests to measure levels of proteins with quick turnaround times can readily be developed to allow for the timely initiation of pharmacologic thromboprophylaxis. 7 In a previous study, we showed that factor VIII activity was associated with incident DVT among critically ill children.…”

Discovery of novel plasma biomarkers for future incident venous thromboembolism by untargeted synchronous precursor selection mass spectrometry proteomics

“…Venous thromboembolism is a complex disease that occurs as a result of interactions between inherited and acquired factors [8]. Several genetic variants and the levels of numerous plasma proteins, mostly with roles in coagulation or fibrinolysis, have been shown to be associated with VTE [1,[9][10][11][12][13][14][15][16][17][18]. However, few prospective studies have successfully shown associations between protein biomarker levels at baseline and risk of future incident VTE [11,13,17,18].…”

Use of viscoelastic tests to predict clinical thromboembolic events: A systematic review and meta‐analysis

“…Many novel coagulation biomarkers have been discovered, but most of these biomarkers are expensive, not widely available, and consequently, far from useful as a practical thromboembolic risk-stratifying tool. 12,13 In vitro whole-blood viscoelastic tests-including thromboelastography (TEG ® ) or rotational thromboelastometry (ROTEM ® )-are widely used in many institutions to identify the mechanisms of bleeding in order to guide blood product transfusion for patients with active bleeding. 13 Emerging evidence suggests that an increase in in vitro clot strength, demonstrated on a viscoelastic test, reflects a hypercoagulable state and may be useful to identify patients who are at increased risk of thromboembolism.…”

“…12,13 In vitro whole-blood viscoelastic tests-including thromboelastography (TEG ® ) or rotational thromboelastometry (ROTEM ® )-are widely used in many institutions to identify the mechanisms of bleeding in order to guide blood product transfusion for patients with active bleeding. 13 Emerging evidence suggests that an increase in in vitro clot strength, demonstrated on a viscoelastic test, reflects a hypercoagulable state and may be useful to identify patients who are at increased risk of thromboembolism. 14,15 We hypothesized that whole-blood viscoelastic tests can differentiate between patients who are hypercoagulable with an increased risk of thromboembolism and those who are not.…”