PB0120 - Plasma profiling of patients on vitamin K antagonists treatment: a targeted quantitative proteomic approach

Background: Despite monitoring, 1-3% of patients treated with vitamin-K antagonists (VKAs) still suffer from a major bleeding annually. Moreover, arterial thromboembolism occurs in 1-2% of patients during treatment. Identification of these patients is suboptimal. There is need to identify novel biomarkers for bleeding and thrombosis during anticoagulation.

Aims: To profile plasma of patients treated with VKA through targeted mass spectrometry(MS) proteomics, to discover novel biomarkers for major bleeding and thrombosis.

Methods: We established a case-cohort study within the BLEEDS cohort, which consisted of 16,570 patients who initiated VKA treatment between 2012-2014. Patients were followed until an event, end of VKA therapy, death or end of study. We included 326 major bleeding and 66 arterial thrombosis cases that occurred during 17,613 patient-years of follow-up and a random subcohort of 414 patients at baseline. Plasma was available from 83% of the subjects. Targeted MS-proteomics with stable isotope-labelled standards allows for reliable quantification of over 100s of proteins in a small volume of plasma. We measured 270 proteins using targeted MS-proteomics, from a diversity of pathways such as coagulation, complement, immunoglobulins, apolipoproteins and inflammation.

Results: Plasma was available for 252 major bleeding, 59 arterial thromboembolic cases and 343 subcohort members. Patients with major bleeding and arterial thrombosis were slightly older (mean age 76 and 77) than patients in the subcohort (mean age 71, Table 1). Measurements were recently completed and analysis is ongoing. We will analyze the protein abundancies through regression and clustering analyses, to identify differences between cases and subcohort.

Conclusion(s): To our knowledge, this is the first effort to quantify more than 100 proteins in a large cohort of anticoagulated patients. The final results are expected in a few months and our data will provide bases for characterization of candidate biomarkers for major bleeding and thrombosis to improve prediction and distinguishing both outcomes.