Chap. 25b Platelet Function and Hemostasis: Key Concepts and Mechanisms

What are the primary stages of platelet activation?

Adhesion, shape change, secretion, and aggregation.

What happens to platelet organelles during the initial stage of activation?

They are reorganized to the center of the platelet before the granules spill their contents into the open canalicular system (OCS).

How do activated platelets amplify the activation process?

Granular contents are released to the outside of the platelet, where they contact and activate adjacent platelets.

What is the role of PGI2 in vascular regulation?

It is synthesized by endothelial cells to antagonize platelet adhesion and aggregation, limiting thrombus formation.

What substance do platelets release to nurture endothelial cells and maintain vascular integrity?

Platelet-derived growth factor (PDGF).

What clinical signs appear in the skin or mucous membranes when platelets are absent?

Petechiae or purpura.

What components of the subendothelial connective tissue matrix facilitate platelet adhesion?

Collagen, vWF, fibronectin, and thrombospondin.

What is the function of von Willebrand factor (vWF) in platelet adhesion?

It acts as a bridge connecting the platelet to subendothelial collagen fibers.

Which platelet membrane receptor is essential for binding to vWF?

GPIb/IX/V.

What condition is caused by a defect in the GPIb/IX/V receptor?

Bernard-Soulier syndrome.

What is the most common autosomal inherited bleeding disorder?

von Willebrand disease.

What is considered the most sensitive parameter of platelet activation?

Shape change.

How do platelets change shape upon activation?

They transform from circulating discs to spheres with pseudopods.

What process transmits external stimuli from the outside of the platelet to the inside?

Signal transduction.

Which two substances are potent platelet agonists that amplify intracellular events?

ADP and TXA2.

What is the function of platelet membrane phospholipid PF3?

It promotes the assembly of vitamin K-dependent factors on the platelet surface.

What is platelet aggregation?

The process of platelet-to-platelet interaction.

What is the primary energy source for platelet aggregation?

ATP derived from glycolysis.

Which glycoprotein complex is required for fibrinogen binding during aggregation?

GPIIb/IIIa.

What role does fibrinogen play in platelet aggregation?

It binds to the GPIIb/IIIa receptors on adjacent platelets, linking them together.

What ions are required for the process of platelet aggregation?

Ionized calcium (Ca2+) and/or magnesium.

What induces the exposure of fibrinogen receptor sites on the platelet membrane?

ADP.

Where is vWF synthesized?

In endothelial cells and megakaryocytes.

When is the GP VI receptor necessary for platelet adhesion?

When injury occurs at a site of increased blood flow.

What are the chemotactic properties of PDGF?

It attracts neutrophils, monocytes, fibroblasts, and smooth muscle cells to the site of injury.

What is the source of fibrinogen when plasma fibrinogen is absent?

Platelet alpha granules

What condition is characterized by a deficiency in GPIIb/IIIa?

Glanzmann's thrombasthenia

What three components are required for in vitro platelet aggregation?

Membrane glycoproteins, fibrinogen, and divalent calcium

What triggers the primary wave of platelet aggregation?

The release of small amounts of ADP from electron-dense granules

What is required for the secondary wave of platelet aggregation?

A strong activation stimulus that evokes secretion of nonmetabolic ADP from electron-dense granules

How is platelet aggregation measured in a standard aggregometer?

By measuring increased light transmittance as optical density decreases

What characterizes the aggregation curve of collagen?

A lag period followed by a single wave of aggregation

What is the term for the irreversible transformation of aggregated platelets into a mass of degenerated material?

Viscous metamorphosis

Name four markers of platelet activation that confirm degranulation of alpha granules.

Beta-thromboglobulin (B-TG), platelet factor 4 (PF4), thrombospondin, and PDGF

How is the hemostatic plug stabilized?

Through the activation of the coagulation cascade and the formation/deposition of fibrin

What role does thrombin play in clot stabilization?

It activates factor XIII, which cross-links fibrin strands

What is the function of t-PA in fibrinolysis?

It catalyzes the conversion of plasminogen to plasmin

What enzyme cleaves membrane phospholipids to free arachidonic acid?

Phospholipase

What enzyme converts arachidonic acid into prostaglandin endoperoxides?

Cyclo-oxygenase

What is the primary function of Thromboxane A2 (TXA2)?

It acts as a potent platelet aggregator, mediator of release, and promoter of vasoconstriction

What is the inactive form of TXA2?

Thromboxane B2 (TXB2)

What is the role of serotonin released from dense bodies?

It acts as a vasoconstrictor and stimulates PGI2 production

How does aspirin affect platelet function?

It irreversibly inhibits cyclo-oxygenase, preventing TXA2 synthesis for the life of the platelet

What are the five stages of platelet plug formation?

Adhesion, aggregation, plug formation, consolidation, and fibrin regulation

What are the four primary actions of thrombin?

Converts fibrinogen to fibrin, activates factor XIII, enhances factors V and VIII, and induces platelet aggregation

Which agonist induces a biphasic wave of aggregation?

Epinephrine

What happens to serotonin-induced aggregation after the initial wave?

It is followed by disaggregation

What is the metabolic cost of platelet aggregation?

It is an energy-dependent process that requires and exhausts ATP resources

What substances are released from dense granules during the release reaction?

ADP, serotonin, and calcium

What is the clinical significance of PAI (plasminogen activator inhibitor)?

It is an inhibitor of t-PA, helping to regulate the fibrinolytic process