PB0146 - Obese patients show enhanced ex vivo collagen-induced thrombus formation in flowing human blood

Sunday, July 10, 2022

6:30 PM – 7:30 PM

Location: Exhibition

Presentation Format: In-Person

Presenting Author(s)

Sara Troitiño

PhD Student
Platelet Proteomics Group, Center for Research in Molecular Medicine and Chronic Diseases (CiMUS), Universidade de Santiago de Compostela, Santiago de Compostela, Spain
Santiago de Compostela, Galicia, Spain

Co-Author(s)

DF

Delia I. Fernández

PhD Student
Department of Biochemistry, CARIM, Maastricht University, 6200 MD Maastricht, The Netherlands
Maastricht, Limburg, Netherlands
Lidia Hermida-Nogueira

PhD
Platelet Proteomics Group, Center for Research in Molecular Medicine and Chronic Diseases (CiMUS), Universidade de Santiago de Compostela, Santiago de Compostela, Spain
Santiago de Compostela, Galicia, Spain
SB

Sandra Buján-Garmendia

MD
Santa Comba Primary Healthcare Center, Santa Comba, Spain
Santa Comba, Galicia, Spain
DL

Dolores López-Fernández

MD
Santa Comba Primary Healthcare Center, Santa Comba, Spain
Santa Comba, Galicia, Spain
AS

Aurelio M. Sueiro

MD
Grupo de Endocrinología Molecular y Celular, Instituto de Investigación Sanitaria de Santiago (IDIS), Servicio de Endocrinología, Xerencia de Xestión Integrada de Santiago (XXS), Santiago de Compostela, Spain
Santiago De Compostela, Galicia, Spain
AG

Angel Garcia

Professor
Universidade de Santiago de Compostela
Santiago de Compostela, Galicia, Spain

Background: We recently demonstrated that platelets from severely obese patients show higher surface expression levels of GPVI and CLEC-2, and up-regulated signaling pathways compared to lean-matched controls, revealing that obesity induces an hyperactivation on platelets (Barrachina et al. ATVB; 2021;41:478–490).

Aims: To evaluate the impact of obesity in thrombus formation and platelet reactivity by using a novel ex vivo microfluidics assay on whole blood.

Methods: Severely obese patients (with no major comorbidities) and lean-matched controls were recruited. Whole-blood microfluidics assays evaluated the shear-dependent thrombus formation process over collagen-H in non-coagulating conditions. Platelet adhesion and activation parameters (integrin activation, P-selectin, and phosphatidylserine exposure) were recorded. Moreover, citrated blood was also perfused over a collagen surface to induce shear-dependent thrombus and fibrin formation, where tissue factor (TF) was partly included to induce activation of the extrinsic coagulation pathway promoting thrombin generation.

Results: In obese patients, increasing thrombus size and volume was observed on collagen. Adhesion parameters were slightly higher in obese patients whereas no major differences between groups were observed in activation parameters. Obese patients showed a slightly more rapid fibrin formation following adhesion to collagen in the presence of TF. In the latter conditions, there were also increased levels in coagulation parameters, such as fibrin formation and phosphatidylserine exposure, in blood from obese patients in comparison to the lean-matched subjects.

Conclusion(s): This is the first study evaluating the effect of obesity on ex vivo collagen-induced thrombus formation in flowing blood under both coagulating and non-coagulating conditions. Overall, we show that obesity enhances the platelet thrombotic phenotype to some extent. These results are in line with our previous studies on washed platelets and confirm an increased atherothrombotic risk in obese patients.