title: Quantification of Shear-Induced Platelet Activation: High Shear Stresses for Short Exposure Time.
abstract: Thrombosis and thromboembolism are the life-threatening clinical complications for patients supported or treated with prosthetic cardiovascular devices. The high mechanical shear stress within these devices is believed to be the major contributing factor to cause platelet activation (PA) and function alteration, leading to thrombotic events. There have been limited quantitative data on how the high mechanical shear stress causes platelet activation. In this study, shear-induced PA in the ranges of well-defined shear stress and exposure time relevant to cardiovascular devices was quantitatively characterized for human blood using two novel flow-through Couette-type blood shearing devices. Four markers of platelet activation-surface P-selectin (CD62p), platelet-derived microparticles (PMPs), platelet-monocyte aggregation (PMA), and soluble P-selectin-were measured by flow cytometry and enzyme-linked immunosorbent assay (ELISA), respectively. The results indicated that PA induced by high shear stresses with short exposure time could be reliably detected with surface P-selectin, and, to a lesser extent, PMPs rather than soluble P-selectin. It was also verified that PMA can be a highly sensitive indirect marker of platelet activation. The quantitative relationship between percentage of activated platelets indicated by surface P-selectin expression and shear stress/exposure time follows well the power law functional form. The coefficients of the power law models of PA based on surface P-selectin expression were derived.
authors: Artificial Organs Laboratory, Department of Surgery, University of Maryland School of Medicine, Baltimore, MD, USA.|Department of Mechanical Engineering, University of Maryland, Baltimore County, Baltimore, MD, USA.
authors: Jun
authors: J
authors: Ding
authors: Artificial Organs Laboratory, Department of Surgery, University of Maryland School of Medicine, Baltimore, MD, USA.
authors: Zengsheng
authors: Z
authors: Chen
authors: Artificial Organs Laboratory, Department of Surgery, University of Maryland School of Medicine, Baltimore, MD, USA.
authors: Shuqiong
authors: S
authors: Niu
authors: Artificial Organs Laboratory, Department of Surgery, University of Maryland School of Medicine, Baltimore, MD, USA.
authors: Jiafeng
authors: J
authors: Zhang
authors: Artificial Organs Laboratory, Department of Surgery, University of Maryland School of Medicine, Baltimore, MD, USA.
authors: Nandan K
authors: NK
authors: Mondal
authors: Artificial Organs Laboratory, Department of Surgery, University of Maryland School of Medicine, Baltimore, MD, USA.
authors: Bartley P
authors: BP
authors: Griffith
authors: Artificial Organs Laboratory, Department of Surgery, University of Maryland School of Medicine, Baltimore, MD, USA.
authors: Zhongjun J
authors: ZJ
authors: Wu
mesh_terms: D001792:Blood Platelets / Q000166:cytology* / Q000473:pathology; D001807:Blood Vessel Prosthesis / Q000009:adverse effects; D055252:Cell-Derived Microparticles / Q000473:pathology; D006350:Heart Valve Prosthesis / Q000009:adverse effects; D006354:Heart, Artificial / Q000009:adverse effects; D006801:Humans; D009000:Monocytes / Q000166:cytology; D019007:P-Selectin / Q000032:analysis; D015539:Platelet Activation; D010979:Platelet Function Tests; D013314:Stress, Mechanical
chemical_list: D019007:P-Selectin; C546937:SELP protein, human
keywords: Blood-shearing device; Exposure time; Power law model; Shear stress; Shear-induced platelet activation