Normal platelet activation profile in patients with peripheral arterial disease on aspirin.

van Geffen, Johanna P; Kleinegris, Marie-Claire; Verdoold, Remco; Baaten, Constance C F M J; Cosemans, Judith M E M; Ten Cate, Hugo; Roest, Mark; de Laat, Bas; Clemetson, Kenneth John; Heemskerk, Johan W M (2015). Normal platelet activation profile in patients with peripheral arterial disease on aspirin. Thrombosis research, 135(3), pp. 513-520. Elsevier 10.1016/j.thromres.2014.12.029

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BACKGROUND Peripheral arterial disease (PAD) is a progressive vascular disease associated with a high risk of cardiovascular morbidity and death. Antithrombotic prevention is usually applied by prescribing the antiplatelet agent aspirin. However, in patients with PAD aspirin fails to provide protection against myocardial infarction and death, only reducing the risk of ischemic stroke. Platelets may play a role in disease development, but this has not been tested by proper mechanistic studies. In the present study, we performed a systematic evaluation of platelet reactivity in whole blood from patients with PAD using two high-throughput assays, i.e. multi-agonist testing of platelet activation by flow cytometry and multi-parameter testing of thrombus formation on spotted microarrays. METHODS Blood was obtained from 40 patients (38 on aspirin) with PAD in majority class IIa/IIb and from 40 age-matched control subjects. Whole-blood flow cytometry and multiparameter thrombus formation under high-shear flow conditions were determined using recently developed and validated assays. RESULTS Flow cytometry of whole blood samples from aspirin-treated patients demonstrated unchanged high platelet responsiveness towards ADP, slightly elevated responsiveness after glycoprotein VI stimulation, and decreased responsiveness after PAR1 thrombin receptor stimulation, compared to the control subjects. Most parameters of thrombus formation under flow were similarly high for the patient and control groups. However, in vitro aspirin treatment caused a marked reduction in thrombus formation, especially on collagen surfaces. When compared per subject, markers of ADP- and collagen-induced integrin activation (flow cytometry) strongly correlated with parameters of collagen-dependent thrombus formation under flow, indicative of a common, subject-dependent regulation of both processes. CONCLUSION Despite of the use of aspirin, most platelet activation properties were in the normal range in whole-blood from class II PAD patients. These data underline the need for more effective antithrombotic pharmacoprotection in PAD.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Haematology and Central Haematological Laboratory
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Unit Childrens Hospital > Forschungsgruppe Hämatologie (Erwachsene)
04 Faculty of Medicine > Pre-clinic Human Medicine > Theodor Kocher Institute

UniBE Contributor:

Clemetson, Kenneth John

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0049-3848

Publisher:

Elsevier

Language:

English

Submitter:

Verena Zwahlen

Date Deposited:

01 May 2015 12:00

Last Modified:

10 May 2016 16:52

Publisher DOI:

10.1016/j.thromres.2014.12.029

PubMed ID:

25600441

BORIS DOI:

10.7892/boris.67694

URI:

https://boris.unibe.ch/id/eprint/67694

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