Related Experiment Video
Updated: Jul 11, 2026
04:32
A Uniform Shear Assay for Human Platelet and Cell Surface Receptors via Cone-plate Viscometry
Published on: June 5, 2019
Differences between activation thresholds for platelet P-selectin glycoprotein IIb-IIIa expression and their clinical
M B Holmes1, B E Sobel, D B Howard
1Department of Medicine, University of Vermont College of Medicine, Burlington 05401, USA. michael.holmes@vtmed.net.org
Thrombosis Research
|July 27, 1999
Summary
Platelet activation thresholds differ for fibrinogen binding and alpha-granule release. Patients with acute coronary syndromes show higher P-selectin expression, indicating increased platelet reactivity despite aspirin use.
Area of Science:
- Cardiovascular Medicine
- Hematology
- Pharmacology
Background:
- Increased platelet reactivity is linked to cardiovascular events.
- Understanding platelet activation pathways is crucial for managing cardiovascular risk.
Purpose of the Study:
- To determine differential activation thresholds for platelet alpha-granule degranulation and fibrinogen binding.
- To assess the effect of aspirin on platelet activation in healthy volunteers and acute coronary syndrome patients.
Main Methods:
- Flow cytometry was used to assess platelet activation in whole blood.
- Fluorescein isothiocyanate conjugated fibrinogen and phycoerythrin conjugated anti-P-selectin antibody were utilized.
- Platelet activation was stimulated with adenosine diphosphate (ADP) or thrombin receptor agonist peptide.
Main Results:
- ADP-induced fibrinogen binding is a low-threshold event, while alpha-granule degranulation (P-selectin expression) is a higher-threshold event.
- Patients with acute coronary syndromes on aspirin exhibited significantly higher ADP-induced P-selectin expression compared to healthy subjects on aspirin.
- No difference in ADP-induced fibrinogen binding was observed between patient and healthy groups.
- Aspirin (325 mg daily) did not affect P-selectin expression or fibrinogen binding in healthy subjects.
Conclusions:
- Flow cytometry effectively characterizes specific components of platelet activation.
- Differential activation thresholds exist for platelet responses.
- Elevated P-selectin expression in acute coronary syndrome patients suggests increased platelet reactivity despite aspirin therapy, highlighting potential targets for antiplatelet drug development.
Related Concept Videos
01:15Activation of Integrins
Integrins bind ligands and transmit information from outside the cell to inside or vice-versa through an "outside-in signaling" or "inside-out signaling."
In "outside-in signaling," external factors in the extracellular space bind to exposed ligand binding sites on integrins. This causes the inactive protein to undergo a conformational change to become active. Integrins are often clustered on the cell membrane. Repetitive and regularly spaced ligand binding events provide an effective stimulus.
In "outside-in signaling," external factors in the extracellular space bind to exposed ligand binding sites on integrins. This causes the inactive protein to undergo a conformational change to become active. Integrins are often clustered on the cell membrane. Repetitive and regularly spaced ligand binding events provide an effective stimulus.
01:17Intracellular Signaling Affects Focal Adhesions
Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
Some...
01:25Selectins
Cell adhesion is an essential aspect of multicellularity. While stable cell interactions usually occur between cells of the same type, transient cell interactions occur between cells of different tissue types, such as between neutrophils and endothelial cells. Selectins are one class of cell adhesion molecules (CAMs) that bind carbohydrate ligands to form transient cell adhesion. They are rod-like proteins with a long extracellular part of variable length ending with the lectin domain, which...
01:20Antiplatelet Drugs: Prostaglandin Synthesis, P2Y12 and Glycoprotein IIb/IIIa Inhibitors
Antiplatelet drugs emerge as frontline defenders against the insidious threat of thromboembolic diseases, where abnormal clots obstruct vital blood vessels. These drugs stand as bulwarks, inhibiting platelet aggregation and clot formation, thereby mitigating the risk of life-threatening conditions like myocardial infarction, coronary artery disease, and thrombotic strokes.
Prostaglandin synthesis inhibitors, exemplified by the widely known aspirin, wield their power by irreversibly acetylating...
Prostaglandin synthesis inhibitors, exemplified by the widely known aspirin, wield their power by irreversibly acetylating...
01:18Structure and Function of Platelets
The cell fragments known as platelets are disc-shaped, with an average diameter of about 3 μm and a thickness of roughly 1 μm. They play a crucial role in the body's vascular clotting system, which also involves plasma proteins, blood cells, and blood vessel tissues.
Platelets are continually replenished, circulating in the bloodstream for 9-12 days before being removed by phagocytes, primarily in the spleen. A microliter of circulating blood contains between 150,000 and 450,000 platelets, with...
Platelets are continually replenished, circulating in the bloodstream for 9-12 days before being removed by phagocytes, primarily in the spleen. A microliter of circulating blood contains between 150,000 and 450,000 platelets, with...
01:22Formation of the Platelet Plug
The platelet phase, the second stage of hemostasis, commences around 15-20 seconds after an injury. It follows and overlaps with the vascular phase, during which blood vessels constrict to minimize blood loss.
As the injured blood vessel contracts, endothelial cells undergo contraction, revealing collagen fibers in the basement membrane and underlying connective tissue. Furthermore, the plasma membrane of endothelial cells becomes adhesive, preparing the site for platelet adhesion. Platelets...
As the injured blood vessel contracts, endothelial cells undergo contraction, revealing collagen fibers in the basement membrane and underlying connective tissue. Furthermore, the plasma membrane of endothelial cells becomes adhesive, preparing the site for platelet adhesion. Platelets...