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Comprehensive platelet phenotyping supports the role of platelets in the pathogenesis of acute venous thromboembolism - results from clinical observation studies
- Source :
- EBioMedicine, Vol 60, Iss, Pp 102978-(2020), EBioMedicine, 60:102978. Elsevier, EBioMedicine
- Publication Year :
- 2020
-
Abstract
- Background: The pathogenesis of arterial and venous thrombosis is in large part interlaced. How much platelet phenotype relates to acute venous thromboembolism (VTE) independent of the underlying cardiovascular profile is presently poorly investigated.Methods: Platelet count and mean platelet volume (MPV), platelet aggregation in whole blood and platelet rich plasma (PRP), platelet-dependent thrombin generation (TG) and platelet surface activation markers were measured under standardized conditions. Machine learning was applied to identify the most relevant characteristics associated with VTE from a large array (N = 58) of clinical and plateletrelated variables.Findings: VTE cases (N = 159) presented with lower platelet count and MPV vs controls (N = 140). Whole blood aggregation showed shorter collagen/Epinephrine closure times in cases, particularly within acetylsalicylic acid (ASA) users. Within ASA users, higher PRP aggregation after adenosine diphosphate (ADP), epinephrine, collagen and arachidonic acid was observed in cases vs controls. Within non-ASA and/or subjects on anticoagulants, cases presented with lower aggregation after ADP and collagen vs controls. Lower platelet-dependent TG, higher CD63 on resting and lower PAC-1 expression after collagen/ADP in-vitro stimulated platelets further characterized VTE cases vs controls, independent of therapy. Lasso regression analysis identified 26 variables associated with VTE of which 69% were platelet-related.Interpretation: 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. Finally, from a large array of covariates including clinical risk factors, platelet biomarkers comprised 69% of all selected variables differentiating VTE cases vs controls.Funding: German Federal Ministry of Education and Research, CTH-Mainz and Bayer AG. (c) 2020 The Authors. Published by Elsevier B.V.
- Subjects :
- Male
0301 basic medicine
Platelet Aggregation
lcsh:Medicine
DETERMINANTS
Gastroenterology
Machine Learning
Pathogenesis
ACTIVATION
0302 clinical medicine
Risk Factors
Platelet
Whole blood
lcsh:R5-920
Aspirin
OUTCOMES
Thrombin
Venous Thromboembolism
General Medicine
Middle Aged
Thrombosis
Venous thrombosis
030220 oncology & carcinogenesis
Acute Disease
Female
Disease Susceptibility
lcsh:Medicine (General)
Research Paper
medicine.drug
Blood Platelets
medicine.medical_specialty
Platelet Function Tests
General Biochemistry, Genetics and Molecular Biology
Immunophenotyping
03 medical and health sciences
ACUTE PULMONARY-EMBOLISM
RISK-FACTOR
Internal medicine
medicine
Humans
Mean platelet volume
METAANALYSIS
Aged
Platelet Count
business.industry
lcsh:R
Platelet Activation
medicine.disease
PREVENTION
ASPIRIN
THROMBOSIS
030104 developmental biology
Platelet-rich plasma
VOLUME
business
Biomarkers
Subjects
Details
- Language :
- English
- ISSN :
- 23523964
- Volume :
- 60
- Database :
- OpenAIRE
- Journal :
- EBioMedicine
- Accession number :
- edsair.doi.dedup.....5b41989ca92fd495e6c67f4dfec4b026