L23 - Platelet Structure and Function

What is Hemostasis?

The regulated process that stops bleeding through coordinated activity of endothelium, platelets, and coagulation factors

Disruption of Hemostasis systems can cause what?

1. Bleeding disorders →  hemorrhage

2. Thrombotic disorders →  aberrant clotting events

What are the Three Phases of Hemostasis?

1. Primary: Vascular damage event →  formation of platelet

2. Secondary: Formation of platelet plug →  formation of fibrin clot

3. Tertiary: Clot remodeling →  dissolution of fibrin clot + vascular repair

What are the Main Functions of Platelets?

1. Primary hemostasis

2. Support of coagulation

3. Immune defense (immunothrombosis)

4. Tissue repair via growth factors

How do Mammalian Platelets Differ from Nonmammalian Thrombocytes?

Functions are comparable.

• Mammalian platelets are anucleate

• Bird, reptile, and fish thrombocytes are nucleated

Where are Platelets Produced, and from Which Cells?

Primarily in bone marrow, from megakaryocytes of the myeloid lineage

• Spleen and lungs also contribute

What is the Megakaryocyte Maturation Sequence?

Megakaryoblast → Promegakaryocyte → Megakaryocyte

What is Endomitosis, and Why is It Important?

DNA replication without cell division

• Increases megakaryocyte DNA content for massive platelet-component synthesis

How are Platelets Released from Megakaryocytes?

Proplatelet extensions enter marrow vessels

• Cytoplasmic beads detach into circulation as platelets

How Many Platelets Can One Megakaryocyte Produce?

Up to approximately 1,000 platelets.

What Regulates Thrombopoiesis?

Mainly thrombopoietin (TPO); IL-6, GM-CSF, IL-11, IL-3, and EPO provide additional stimulation.

Where is Thrombopoietin (TPO) Produced?

Primarily hepatocytes in the liver; smaller amounts from kidneys and bone marrow stromal cells.

How Does Platelet Mass Regulate Free TPO?

Low platelet mass → less TPO clearance → more free TPO → increased megakaryocyte stimulation.

What are the Effects of TPO on Megakaryocytes?

Increases megakaryocyte numbers, size, maturation, and endomitosis, raising platelet production.

What is the Normal Platelet Life Cycle?

Circulate about 4–6 days; ~30% reside in splenic reserve. Aging platelets lose sialic acid and are cleared mainly by liver.

What is the Role of Phosphatidylserine in Platelets?

Activation exposes negatively charged phosphatidylserine, creating a procoagulant surface for coagulation factors.

What are the Functions of GPIb, GPVI, and GPIIb/IIIa?

GPIb binds vWF; GPVI binds collagen; activated GPIIb/IIIa binds fibrinogen to cross-link platelets.

How Does the Platelet Cytoskeleton Change during Activation?

Actin and microtubules reorganize; discoid platelets become spiny, extend projections, then spread flat.

What are the Functions of Platelet Tubular Systems?

Open canalicular: granule secretion. Dense tubular: calcium storage/release and TXA2 synthesis.

How Do Alpha and Dense Granules Differ?

Alpha: adhesion proteins, integrins, coagulation factors, growth factors. Dense: ADP, calcium, serotonin.

What is the Sequence of Primary Hemostasis?

Platelet adhesion → activation and secretion → aggregation → temporary platelet plug.

How Does Healthy Endothelium Prevent Platelet Activation?

PGI2 and nitric oxide suppress platelet activity; endothelial ADPase degrades activating ADP.

What Happens Immediately after Vascular Injury?

Reflex vasoconstriction reduces blood loss; exposed subendothelial collagen and vWF permit platelet adhesion.

How Do Platelets Adhere to Damaged Vasculature?

GPIb binds subendothelial vWF for initial tethering; GPVI binds exposed collagen for further anchoring.

What Signals Trigger Platelet Activation?

Adhesion through GPIb–vWF and GPVI–collagen, plus soluble ADP, TXA2, and thrombin.

What are the Main Consequences of Platelet Activation?

Shape change, granule secretion, TXA2 synthesis, recruitment of other platelets, and aggregation.

How Do Platelet Granules Amplify Activation?

Dense granules release ADP, calcium, and serotonin; alpha granules supply adhesion and coagulation-related proteins.

How is Thromboxane A2 (TXA2) Produced?

De novo from arachidonic acid via cyclooxygenase-1 (COX-1).

What is the Function of TXA2, and How Does Aspirin Affect It?

TXA2 recruits and activates platelets; aspirin irreversibly inhibits COX-1, decreasing TXA2 synthesis.

Why Do Activated Platelets Change Shape?

Spiny projections increase attachment and platelet contact; later flattening covers injury and supports coagulation.

How Does Platelet Aggregation Occur?

Activation raises GPIIb/IIIa affinity for fibrinogen, which bridges adjacent platelets into a plug.

What is the Difference between Platelet Adhesion and Aggregation?

Adhesion: platelets attach to injured vessel via GPIb–vWF/GPVI–collagen. Aggregation: platelets bind each other via fibrinogen–GPIIb/IIIa.

How Do Platelets Support Secondary Hemostasis?

Exposed phosphatidylserine and calcium dock coagulation factors; fibrin forms over and stabilizes the platelet plug.