Hemostasis: Lesson 2 - Platelet Activation and Aggregation

Summary

This lecture focuses on the first part of normal hemostasis physiology, detailing primary hemostasis and platelet activation. The video explains endothelial cell functions that prevent inappropriate thrombosis, such as the secretion of prostacyclin, nitric oxide, and other anti-coagulant proteins. It covers platelet formation, structure, and function, and explores the role of Von Willebrand factor in platelet adhesion and aggregation. Key triggers of platelet activation, including collagen, ADP, thromboxane A2, and thrombin, are discussed, alongside the consequences of platelet activation in clot formation. The synthesis of thromboxane A2 and its relationship with prostacyclin, as well as the action of aspirin, is also explored.

Takeaways

• 😀 Endothelial cells play a crucial role in preventing thrombosis by secreting prostacyclin (PGI2) and nitric oxide to inhibit platelet activation.
• 😀 Platelets are derived from megakaryocytes in the bone marrow and have a lifespan of about 10 days in circulation.
• 😀 Platelets lack a nucleus but contain granules (alpha and dense) that are important for adhesion, activation, and aggregation.
• 😀 Von Willebrand factor (VWF) is essential for platelet adhesion and aggregation by binding to collagen and platelet receptors.
• 😀 Platelet activation occurs through receptors like GP1b/59 (binds VWF), GP6, GP1a2a (binds collagen), and GP2b/3a (binds fibrinogen).
• 😀 The major triggers for platelet activation include subendothelial collagen, ADP, thromboxane A2, and thrombin.
• 😀 Platelet aggregation begins after activation, leading to the formation of a platelet plug, which is vital for stopping bleeding.
• 😀 Activated platelets undergo a shape change, becoming more irregular to increase their surface area and enhance platelet-to-platelet interaction.
• 😀 Platelet activation leads to the exposure of phosphatidylserine on the outer membrane, aiding in clotting factor assembly.
• 😀 Thromboxane A2 and prostacyclin have opposing actions in hemostasis, with thromboxane promoting platelet activation and vasoconstriction, while prostacyclin inhibits platelet activation and causes vasodilation.

Q & A

What is the primary focus of this lecture on hemostasis?

The lecture focuses on primary hemostasis, specifically endothelial function, platelet formation, structure, and the triggers and consequences of platelet activation.

What are the functions of endothelial cells in preventing inappropriate thrombosis?

Endothelial cells secrete prostacyclin (PGI2), nitric oxide, and heparin sulfate, and express thrombomodulin and tissue factor pathway inhibitor to prevent spontaneous thrombosis.

What role does prostacyclin play in hemostasis?

Prostacyclin inhibits platelet activation and aggregation, helping to prevent inappropriate thrombosis.

How do endothelial cells react after vascular injury?

After vascular injury, endothelial cells react by secreting substances that promote clot formation, like von Willebrand factor, which aids in platelet adhesion and aggregation.

Where do platelets originate and what is their structure?

Platelets originate from megakaryocytes in the bone marrow. They are cytoplasmic fragments, lack a nucleus, and have few organelles but a complex cytoskeleton and membrane structure.

What are the primary types of membrane receptors found on platelets?

The primary platelet receptors are the GP1b/59 complex, GP1a/2a (integrin alpha 2 beta 1), GP6, and GP2b/3a (integrin alpha 2B beta 3). These receptors are involved in platelet adhesion, activation, and aggregation.

What is von Willebrand factor and how does it function?

Von Willebrand factor (vWF) is a large glycoprotein that binds to collagen, GP1b/59 receptor, and other clotting factors, playing a key role in platelet adhesion and aggregation as well as in coagulation by stabilizing factor 8.

What is the significance of platelet activation triggers like collagen and ADP?

Collagen and ADP are key triggers for platelet activation. Collagen exposure after vascular injury initiates platelet adhesion, and ADP, secreted by activated platelets, enhances their activation locally in an autocrine or paracrine manner.

How do platelets change upon activation?

Upon activation, platelets undergo a shape change, transitioning from a discoid form to a highly irregular shape with numerous projections, which increases their surface area and ability to aggregate.

What is the role of thromboxane A2 in platelet activation?

Thromboxane A2, synthesized by activated platelets, promotes further platelet activation, vasoconstriction, and aggregation, acting in an autocrine or paracrine manner to amplify the platelet response.