Comprehensive Platelet Phenotyping Supports the Role of Platelets in the Pathogenesis of Acute Venous Thromboembolism - Results from Clinical Observational Studies

M. Panova-Noeva^1,2, B. Wagner³, M. Nagler³, V. ten Cate³, J. Prochaska^1,2,3, S. Heitmeier⁴, I. Meyer⁴, C. Gerdes⁴, V. Laux⁴, S. Konstantinides⁵, H. Spronk⁶, K. Lackner⁷, K. Leineweber⁴, H. ten Cate⁶, P. Wild^1,2,3

¹Clinical Epidemiology and Systems Medicine, Center for Thrombosis and Hemostasis (CTH), University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany, ²DZHK (German Center for Cardiovascular Research), Partner Site Rhine-Main, Mainz, Germany, ³Preventive Cardiology and Preventive Medicine, Center for Cardiology, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany, ⁴Bayer AG, Wuppertal, Germany, ⁵Clinical Trials, Center for Thrombosis and Hemostasis (CTH), University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany, ⁶Laboratory for Clinical Thrombosis and Hemostasis, Department of Internal Medicine, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Center, the Netherlands, Maastricht, the Netherlands, ⁷Institute for Clinical Chemistry and Laboratory Medicine, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany

Abstract Number: PB0450

Meeting: ISTH 2020 Congress

Theme: Diagnostics and OMICs » Biomarkers of Thrombosis and Hemostasis

Background: The pathogenesis of arterial and venous thrombosis is in large part interlaced, however to which extend platelet function relates to acute venous thromboembolism (VTE) independent of the underlying cardiovascular profile is presently poorly investigated.

Aims: To compare platelet function variables between VTE cases and controls and to identify the most relevant characteristics associated with VTE from a large array (N=58) of clinical risk factors and platelet variables.

Methods: Platelet count, mean platelet volume (MPV), platelet aggregation in whole blood and by the light transmission aggregometry (LTA) in platelet rich plasma, platelet-dependent thrombin generation (TG) and platelet surface activation markers by flow cytometry were measured under standardized conditions.

Results: VTE cases (N=155) presented with lower platelet count and MPV compared to controls (N=139). Whole blood aggregation showed shorter collagen/Epinephrine closure times in cases, particularly within acetylsalicylic acid (ASA) users. LTA results were distinct according to therapy; within ASA users, higher aggregation response after adenosine diphosphate (ADP), epinephrine, collagen and arachidonic acid was observed in cases vs controls. Within non-ASA users and/or subjects on anticoagulants, cases presented with lower aggregation after ADP and collagen vs controls. Lower platelet-dependent TG, higher platelet CD63 surface expression on resting platelets and lower PAC-1 expression after collagen/ADP in vitro stimulation further characterized VTE cases vs controls, independent of therapy. Lasso regression analysis identified 34 variables associated with VTE. Platelet related-biomarkers comprised 76% of the variables selected and presented with the highest predictive strength.

Conclusions: Comprehensive phenotyping of platelet function identified a large proportion of low responders to ASA in VTE cases. Lower platelet-dependent TG and lower platelet reactivity after ex-vivo stimulation characterized the “platelet exhausted syndrome” in cases compared to controls. Finally, from a large array of covariates including clinical profile, platelet biomarkers comprised 76% of all selected variables differentiating VTE cases vs controls.

To cite this abstract in AMA style:

Panova-Noeva M, Wagner B, Nagler M, ten Cate V, Prochaska J, Heitmeier S, Meyer I, Gerdes C, Laux V, Konstantinides S, Spronk H, Lackner K, Leineweber K, ten Cate H, Wild P. Comprehensive Platelet Phenotyping Supports the Role of Platelets in the Pathogenesis of Acute Venous Thromboembolism – Results from Clinical Observational Studies [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/comprehensive-platelet-phenotyping-supports-the-role-of-platelets-in-the-pathogenesis-of-acute-venous-thromboembolism-results-from-clinical-observational-studies/. Accessed January 23, 2022.

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