TY - JOUR
T1 - Exploration of the plasma proteomic profile of patients at risk of thromboembolic events
AU - Smit, Eva R.
AU - Kreft, Iris C.
AU - Camilleri, Eleonora
AU - in collaboration with BEAT-COVID group and Dutch COVID & Thrombosis Coalition
AU - Burggraaf-van Delft, J. Louise I.
AU - van Rein, Nienke
AU - van Vlijmen, Bart J.M.
AU - Hulshof, Anne Marije
AU - van Bussel, Bas C.T.
AU - van Rosmalen, Frank
AU - van der Zwaan, Carmen
AU - van de Berg, Tom
AU - Henskens, Yvonne
AU - ten Cate, Hugo
AU - Coutinho, Jonathan M.
AU - Kruip, Marieke J.H.A.
AU - Eikenboom, Jeroen
AU - Hoogendijk, Arie J.
AU - Cannegieter, Suzanne
AU - van den Biggelaar, Maartje
AU - Arbous, M. Sesmu
AU - van den Berg, Bernard M.
AU - Cannegieter, Suzanne
AU - Cobbaert, Christa M.
AU - van der Does, Anne M.
AU - van Dongen, Jacques J.M.
AU - Eikenboom, Jeroen
AU - Feltkamp, Mariet C.W.
AU - Geluk, Annemieke
AU - Goeman, Jelle J.
AU - Giera, Martin
AU - Hankemeier, Thomas
AU - Heemskerk, Mirjam H.M.
AU - Hiemstra, Pieter S.
AU - Hokke, Cornelis H.
AU - Janse, Jacqueline J.
AU - Jochems, Simon P.
AU - Joosten, Simone A.
AU - Kikkert, Marjolein
AU - Lamont, Lieke
AU - Manniën, Judith
AU - Ottenhoff, Tom H.M.
AU - Pongracz, T.
AU - del Prado, Michael R.
AU - Roestenberg, Meta
AU - Roukens, Anna H.E.
AU - Smits, Hermelijn H.
AU - Snijder, Eric J.
AU - Staal, Frank J.T.
AU - Trouw, Leendert A.
AU - Tsonaka, Roula
N1 - Publisher Copyright: © 2025 The Authors
PY - 2025/2
Y1 - 2025/2
N2 - Background: The elevated health burden of thromboembolic events necessitates development of blood-based risk monitoring tools. Objectives: We explored the potential of mass spectrometry–based plasma proteomics to provide insights into underlying plasma protein signatures associated with treatment and occurrence of thromboembolic events. Methods: Utilizing a high-throughput, data-independent acquisition, discovery-based proteomics workflow, we analyzed 434 plasma proteomes from different groups of individuals with elevated risk of thromboembolic events, including individuals I) on vitamin K antagonists (VKAs; n = 130), II) with a prior venous thromboembolism (n = 10), III) with acute cerebral venous sinus thrombosis (n = 10, and IV) with SARS-CoV-2 infection (n = 67). Plasma protein levels measured with mass spectrometry were correlated with international normalized ratio and conventional clinical laboratory measurements. Plasma profile differences between different groups were assessed using principal component analysis, moderated t-test, and clustering analysis. Results: Plasma protein levels were in agreement with conventional clinical laboratory parameters, including albumin and fibrinogen. Levels of vitamin K–dependent proteins inversely correlated with international normalized ratio. In the individual studies, we found decreased levels of vitamin K–dependent coagulation proteins in patients on VKAs, alterations in inflammatory signatures among CVST patients and a distinctive signature indicative of SARS-CoV-2 infection. However, no protein signature associated with a thromboembolic event could be identified neither in individual nor combined studies. Conclusion: Although VKA treatment–specific and disease-specific signatures were captured, our study highlights that the challenges of discovering biomarkers in patients at risk of thromboembolic events lie in the heterogeneity of individual plasma profiles in relation to treatment and etiology.
AB - Background: The elevated health burden of thromboembolic events necessitates development of blood-based risk monitoring tools. Objectives: We explored the potential of mass spectrometry–based plasma proteomics to provide insights into underlying plasma protein signatures associated with treatment and occurrence of thromboembolic events. Methods: Utilizing a high-throughput, data-independent acquisition, discovery-based proteomics workflow, we analyzed 434 plasma proteomes from different groups of individuals with elevated risk of thromboembolic events, including individuals I) on vitamin K antagonists (VKAs; n = 130), II) with a prior venous thromboembolism (n = 10), III) with acute cerebral venous sinus thrombosis (n = 10, and IV) with SARS-CoV-2 infection (n = 67). Plasma protein levels measured with mass spectrometry were correlated with international normalized ratio and conventional clinical laboratory measurements. Plasma profile differences between different groups were assessed using principal component analysis, moderated t-test, and clustering analysis. Results: Plasma protein levels were in agreement with conventional clinical laboratory parameters, including albumin and fibrinogen. Levels of vitamin K–dependent proteins inversely correlated with international normalized ratio. In the individual studies, we found decreased levels of vitamin K–dependent coagulation proteins in patients on VKAs, alterations in inflammatory signatures among CVST patients and a distinctive signature indicative of SARS-CoV-2 infection. However, no protein signature associated with a thromboembolic event could be identified neither in individual nor combined studies. Conclusion: Although VKA treatment–specific and disease-specific signatures were captured, our study highlights that the challenges of discovering biomarkers in patients at risk of thromboembolic events lie in the heterogeneity of individual plasma profiles in relation to treatment and etiology.
UR - http://www.scopus.com/inward/record.url?scp=105000600450&partnerID=8YFLogxK
U2 - 10.1016/j.rpth.2025.102713
DO - 10.1016/j.rpth.2025.102713
M3 - Article
AN - SCOPUS:105000600450
SN - 2475-0379
VL - 9
JO - Research and Practice in Thrombosis and Haemostasis
JF - Research and Practice in Thrombosis and Haemostasis
IS - 2
M1 - 102713
ER -