Increased Platelet Adhesiveness in Patients with Venous Thromboembolic Disease

<b>Background</b> Association between global platelet function and the risk of venous thromboembolic disease (VTE) has been proposed, though the mechanisms do not involve increased platelet aggregation. However, platelet adhesiveness has not been systematically explored in VTE patients. <b>Objectives</b> To evaluate platelet adhesive functions in VTE patients. <b>Methods</b> Platelet adhesion was evaluated by using whole blood samples from VTE patients, selected based on short closure times on the PFA-100 ( <i>n</i> = 54), and matched healthy individuals ( <i>n</i> = 57) in: (i) the PFA-100, (ii) a cone plate analyzer (CPA), on a plastic surface, (iii) microfluidic devices, with two- and three-dimensional evaluation, and (iv) membrane glycoprotein analysis. Intraplatelet signaling was evaluated in isolated collagen type I (Col-I) activated platelets and platelets adhered on Col-I or von Willebrand factor (VWF) coated coverslips under flow. VWF antigen and ADAMTS-13 activity were measured in plasma samples. <b>Results</b> PFA-100 closure times remained significantly shorter in patients. The CPA test showed a significant increase in the platelet aggregates size when using blood from VTE patients. Platelet adhesion on Col-I revealed a higher area covered by platelets and increased aggregate volume when exposed to samples from VTE patients. Protein P-ZAP70/SYK72 showed a phosphorylation level significantly increased in patients' platelets. Plasma VWF was significantly elevated in VTE patients. <b>Conclusions</b> Platelets from VTE patients exhibit a proadhesive phenotype under flow conditions potentially related to the shortened occlusion times with the PFA-100. This enhanced adhesiveness may be explained by higher intraplatelet ZAP70/SYK72 phosphorylation and increased plasma VWF in patients. Therefore, primary hemostasis plays a significant role in the pathophysiology of VTE.

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Publication Details

Journal
TH Open
Published
2024-10-01
DOI
https://doi.org/10.1055/s-0044-1800798
Primary Topic
Platelet Disorders and Treatments
Type
article
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article

Increased Platelet Adhesiveness in Patients with Venous Thromboembolic Disease

Didac Jerez-Dolz, Pablo Sánchez, Francisco Vidal, Laura Martín-Fernández et al.
TH Open
Platelet Disorders and Treatments
article

Increased Platelet Adhesiveness in Patients with Venous Thromboembolic Disease

Didac Jerez-Dolz, Pablo Sánchez, Francisco Vidal, Laura Martín-Fernández, Juan Carlos Souto, Ginés Escolar, Sergi Torramadé‐Moix, José Manuel Soria, Julia Martínez-Sánchez, Ana Belén Moreno‐Castaño, Mercedes Camacho, Sergi Mojal, Carla Moret, Maribel Díaz‐Ricart, Marta Palomo, Dolors Llobet, Marina Carrasco
article en

Abstract

<b>Background</b> Association between global platelet function and the risk of venous thromboembolic disease (VTE) has been proposed, though the mechanisms do not involve increased platelet aggregation. However, platelet adhesiveness has not been systematically explored in VTE patients. <b>Objectives</b> To evaluate platelet adhesive functions in VTE patients. <b>Methods</b> Platelet adhesion was evaluated by using whole blood samples from VTE patients, selected based on short closure times on the PFA-100 ( <i>n</i> = 54), and matched healthy individuals ( <i>n</i> = 57) in: (i) the PFA-100, (ii) a cone plate analyzer (CPA), on a plastic surface, (iii) microfluidic devices, with two- and three-dimensional evaluation, and (iv) membrane glycoprotein analysis. Intraplatelet signaling was evaluated in isolated collagen type I (Col-I) activated platelets and platelets adhered on Col-I or von Willebrand factor (VWF) coated coverslips under flow. VWF antigen and ADAMTS-13 activity were measured in plasma samples. <b>Results</b> PFA-100 closure times remained significantly shorter in patients. The CPA test showed a significant increase in the platelet aggregates size when using blood from VTE patients. Platelet adhesion on Col-I revealed a higher area covered by platelets and increased aggregate volume when exposed to samples from VTE patients. Protein P-ZAP70/SYK72 showed a phosphorylation level significantly increased in patients' platelets. Plasma VWF was significantly elevated in VTE patients. <b>Conclusions</b> Platelets from VTE patients exhibit a proadhesive phenotype under flow conditions potentially related to the shortened occlusion times with the PFA-100. This enhanced adhesiveness may be explained by higher intraplatelet ZAP70/SYK72 phosphorylation and increased plasma VWF in patients. Therefore, primary hemostasis plays a significant role in the pathophysiology of VTE.

TH OpenVol. 08(04)
Universitat Autònoma de Barcelona (ES), Instituto de Salud Carlos III (ES), Hospital de Sant Pau (ES), Centro de Investigación en Red en Enfermedades Cardiovasculares (ES), Vall d'Hebron Institut de Recerca (ES), Institut Català de Ciències del Clima (ES), Centre for Biomedical Network Research on Rare Diseases (ES), Centro de Investigación Biomédica en Red (ES), Hospital Clínic de Barcelona (ES), Institut de Ciències del Mar (ES), Banc de Sang i Teixits (ES), Consorci Institut D'Investigacions Biomediques August Pi I Sunyer (ES), Instituto de Investigación de Enfermedades Raras (ES), Universitat de Barcelona (ES)
Fundació la Marató de TV3, Ministerio de Ciencia, Innovación y Universidades, Generalitat de Catalunya, José Carreras Leukämie-Stiftung, Ministerio de Asuntos Económicos y Transformación Digital, Gobierno de España, Centro de Investigación Biomédica en Red Enfermedades Cardiovasculares, Agència de Gestió d'Ajuts Universitaris i de Recerca, Instituto de Salud Carlos III, European Regional Development Fund
Good health and well-being
Openalex Percentile: Top 65%
Platelet Disorders and Treatments
DOIOpen Access PDFOpenAlex
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