Variation of platelet function in clinical phenotypes of acute venous thromboembolism - Results from the GMP-VTE project

Marina Panova-Noeva; Bianca Wagner; Markus Nagler; Thomas Koeck; Vincent Ten Cate; Lisa Eggebrecht; Jürgen H Prochaska; Imke Meyer; Christoph Gerdes; Henri M Spronk; Karl J Lackner; Hugo Ten Cate; Kirsten Leineweber; Stefan Heitmeier; Stavros Konstantinides; Philipp S Wild

doi:10.1111/jth.15595

Variation of platelet function in clinical phenotypes of acute venous thromboembolism - Results from the GMP-VTE project

J Thromb Haemost. 2022 Mar;20(3):705-715. doi: 10.1111/jth.15595. Epub 2021 Dec 1.

Authors

Marina Panova-Noeva^{1

2

3}, Bianca Wagner², Markus Nagler², Thomas Koeck², Vincent Ten Cate², Lisa Eggebrecht², Jürgen H Prochaska^{1

2

3}, Imke Meyer⁴, Christoph Gerdes⁴, Henri M Spronk⁵, Karl J Lackner^{3

6}, Hugo Ten Cate⁵, Kirsten Leineweber⁴, Stefan Heitmeier⁴, Stavros Konstantinides¹, Philipp S Wild^{1

2

3}

Affiliations

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

PMID: 34784445
DOI: 10.1111/jth.15595

Abstract

Background: The role of platelets in the pathogenesis of venous thromboembolism (VTE) is receiving increasing attention; however, limited information is available on platelet function in the acute phase of the disease.

Objective: To characterize platelet function according to VTE phenotypes.

Patients/methods: In total, 154 subjects (isolated pulmonary embolism [iPE], n = 28; isolated deep vein thrombosis [iDVT], n = 35; DVT+PE, n = 91) were included. In this study platelet function analyzer (PFA)-200, light transmission aggregometry (LTA), thrombin generation (TG) in presence (PRP) and absence (PFP) of platelets and platelet flow cytometry were investigated. LASSO regression was used to select clinical and platelet biomarkers that distinguish between VTE phenotypes.

Results: PFA-200 results did not differ between VTE phenotypes. LTA from DVT+PE subjects showed lowest maximum aggregation after epinephrine and adenosine diphosphate compared to iPE and iDVT. Lower % of PAC-1-positive platelets after in-vitro trigger were present in DVT+PE and iPE compared to iDVT. TG in PRP had lower peak height and velocity in DVT+PE and iPE against iDVT. The results of LASSO regression for the distinction between DVT+PE vs iDVT identified 18 variables (AUC =0.93) of which 72% were platelet biomarkers. For distinction between iPE and iDVT, 10 variables were selected (AUC = 0.96) of which 50% were platelet-related. Obesity was the only variable weakly discriminating between DVT+PE vs iPE (AUC = 0.66).

Conclusion: This explorative study suggests an important distinction between PE-related phenotypes and iDVT when considering clinical and platelet function data. Lower platelet-dependent TG along with reduced platelet reactivity suggest higher platelet degranulation in PE-dependent phenotypes compared to iDVT.

Keywords: deep vein thrombosis; platelet function; pulmonary embolism; thrombin generation; venous thromboembolism.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Humans
Phenotype
Platelet Function Tests
Pulmonary Embolism* / diagnosis
Venous Thromboembolism* / diagnosis
Venous Thromboembolism* / genetics
Venous Thrombosis* / diagnosis