Primäre Hämostase - Teil 2 - Physiologie und Medikamente - AMBOSS Auditor

Summary

This video provides an in-depth explanation of primary hemostasis, focusing on platelet activation and aggregation. It describes the roles of von Willebrand factor, ADP, and thromboxane A2 in initiating and amplifying platelet activation. The video explores how various medications, like aspirin, clopidogrel, and GPIIb/IIIa inhibitors, influence platelet function, emphasizing their use in preventing arterial thrombosis and managing acute coronary syndromes. Additionally, it contrasts the conditions and treatment approaches for arterial and venous thrombosis, highlighting the importance of anticoagulants for venous thromboembolism and combination therapy for arterial thrombi.

Takeaways

• 😀 Platelet activation begins with adhesion to von Willebrand factor, causing a shape change from a flat disc to protrusions, enabling better interaction with wounds and other platelets.
• 😀 ADP (Adenosine diphosphate) is released by activated platelets, which further activates other platelets, leading to a positive feedback loop that accelerates platelet activation.
• 😀 Thromboxane A2 (TxA2) is another crucial mediator released by platelets that enhances vasoconstriction and further activates platelets to form a clot.
• 😀 The GPIIb/IIIa receptor on platelets plays a central role in platelet aggregation by binding fibrinogen, linking platelets together to form a white thrombus.
• 😀 Platelet aggregation inhibitors, such as aspirin (ASS) and clopidogrel, are used to prevent arterial thrombus formation by blocking platelet activation and aggregation.
• 😀 Aspirin irreversibly inhibits COX-1, preventing thromboxane A2 production, with an effect that lasts up to 7 days, as long as the platelet lifespan.
• 😀 Clopidogrel, an ADP receptor blocker, prevents platelet activation and aggregation, with a similar irreversibility and a duration of action matching platelet lifespan.
• 😀 Ibuprofen also inhibits COX-1 but reversibly, meaning its effects wear off within 24 to 48 hours, and it should not be combined with aspirin for optimal platelet inhibition.
• 😀 GPIIb/IIIa inhibitors, such as tirofiban, block fibrinogen binding to platelets, preventing aggregation. These are often used in acute coronary syndromes and can only be administered parenterally.
• 😀 In arterial thrombus prevention, antiplatelet drugs are preferred, while venous thrombus prevention typically involves anticoagulants that target the coagulation cascade rather than platelets.

Q & A

What initiates the activation of platelets in primary hemostasis?

The activation of platelets begins with their binding to the von Willebrand factor, which causes a shape change in the platelets, transforming them from a flat disc to a form with thin extensions that improve their interaction with each other and the wound site.

What is the role of ADP in platelet activation?

ADP (adenosine diphosphate) is released from activated platelets and binds to ADP receptors on other platelets, further activating them. This creates a positive feedback loop, amplifying the activation of platelets.

How does thromboxane A2 contribute to platelet function?

Thromboxane A2 (TxA2) has two main effects: it enhances vasoconstriction of blood vessels and activates additional platelets, helping to seal the wound. TxA2 is synthesized in platelets by cyclooxygenase-1 (COX-1).

What is platelet aggregation, and how does it occur?

Platelet aggregation is the process in which activated platelets bind together through fibrinogen, which binds to the glycoprotein IIb/IIIa receptors on their surfaces. This results in the formation of a relatively unstable aggregate of platelets.

What role does the glycoprotein IIb/IIIa receptor play in platelet aggregation?

The glycoprotein IIb/IIIa receptor is crucial for platelet aggregation because it allows fibrinogen to bind to platelets, linking them together. This receptor is the most abundant on the platelet surface.

What is the significance of aspirin (ASS) in platelet aggregation inhibition?

Aspirin (ASS) inhibits the enzyme cyclooxygenase-1 (COX-1) in platelets, preventing the synthesis of thromboxane A2, which is essential for platelet activation. The inhibition is irreversible, meaning the effects last until new platelets are produced.

How does clopidogrel differ from aspirin in its mechanism of action?

Clopidogrel works by blocking the ADP receptors on platelets, preventing further platelet activation. Like aspirin, the effect is irreversible, lasting the lifespan of the platelet, which is about 7 days.

Why should aspirin and ibuprofen not be taken together for cardiovascular protection?

Ibuprofen reversibly inhibits COX-1, while aspirin irreversibly inhibits it. If both are taken together, the effects of aspirin are diminished, as some COX-1 molecules will regain their function, reducing the desired platelet aggregation inhibition.

What are GPIIb/IIIa inhibitors, and when are they used?

GPIIb/IIIa inhibitors, like tirofiban, prevent platelet aggregation by blocking fibrinogen from binding to platelets. These inhibitors are used in acute coronary syndromes and are administered parenterally in hospital settings.

How do the conditions in the arterial and venous systems differ in terms of thrombosis prevention?

In the arterial system, high blood flow speeds make platelet aggregation the main contributor to thrombosis, so platelet aggregation inhibitors are used. In contrast, in the venous system, slower blood flow leads to a higher risk of fibrin clot formation, requiring anticoagulants instead of platelet inhibitors.