Intro to Coagulation and Primary Hemostasis

What are the three stages of Normal Coagulation?

Primary Hemostasis, Secondary Hemostasis, and Fibrinolysis

What happens in the Primary Hemostasis stage?

After the injury to the blood vessels, the vessels constrict to minimize blood flow and platelets accumulate to form a fragile platelet plug

What happens in the Secondary Hemostasis stage?

Coagulation factors make fibrin and deposit it at plug to reinforce and stabilize it —→ The blood clot

What happens in the Fibrinolysis stage?

After the wound is healed, the clot is broken down and removed

For the Capillary, what are the breach sealing requirements?

Generally direct sealing

For the Venule, what are the breach sealing requirements?

Mostly fused platelets

For the Arteriole, what are the breach sealing requirements?

Mostly fused platelets

For the Vein, what are the breach sealing requirements?

Vascular contraction, fused platelets, extrinsic and intrinsic factor activation

For the Artery, what are the breach sealing requirements?

Great vascular contraction, more fused platelets, greater extrinsic and intrinsic factor activation

The outer layer of the platelet?

Tunic adventitia

The middle layer of the platelet?

Tunica media

The inner layer of the platelet?

Tunica intima

This is the default state that discourages activation of platelets and formation of thrombi?

Resting

This is the state in response to injury and encourages the formation of thrombi?

Activated

These substances are for which state of function?

• Prostacyclin (PGI2)

• Nitric Oxide (NO)

• ADPase

Resting state

Prostacyclin is a…

powerful platelet inhibitors

Nitric Oxide is a…

Vasodilator

ADPase is a…

Enzyme that degrades ADP, which is a platelet activator

Receptors in the resting state play a role for…

circulating controls that inhibit coagulation and the activation of fibrinolysis

What are the substances that have role in activated state?

• Thromboxane (TXA2), Platelet Activating Factor (PAF), and endothelin (ET) - Activate Platelets

• Tissue factor (TF) - Activate 2nd hemostasis

  • Plasminogen activator inhibitor 1 (PAI-1) - inhibit fibrinolysis

What role do receptors play in the activated state?

While not technically a receptor, the exposed collagen from vessel damage acts as substrate for platelets to adhere to

Platelets participate in hemostasis by:

• releasing substances that mediate vasoconstriction, platelet adhesion, activation and aggregation which leads to the formation of the platelet plug. Platelets also have receptors (PRIMARY)

• Provide phospholipid surface for factor X and prothrombin activation (SECONDARY)

Platelets have 4 zones

1. Peripheral

2. Sol-Gel/Structural

3. Organelle

4. Membrane Systems

What is the thick outer coating of the Peripheral zone?

The glycocalyx

How does the glycocalyx help platelets repel one another in the resting state?

A negative surface charge

What does the cell membrane in the peripheral zone of the platelet do?

Rapidly redistribute phospholipids after activation via scramblase to achieve a neutral charge and facilitate platelet to platelet interaction

The Sol-Gel/Structural Zone “Cytoskeleton) is responsible for what?

The microtubules/microfilaments/sub-membraneous filaments are responsible for the pseudopod formation when activated. They reorganize and change change, Actin and myosin also contribute to shape change.

In the Organelle zone, what two things support metabolism?

Mitochondria and Glycogen particles (granules)

What are four different types of granules in the organelle zone?

• Alpha- loads of contents (fibrinogen)

• Dense- non protein contents (calcium)

• Lysosomes-hydrolytic enzymes

• Peroxisomes- lipid metabolism

What does the membrane systems zone of the platelet consist of?

Open Canalicular systems and Dense Tubular systems

The Open Canalicular system are used for…

entry for external substances and surface to release granules

The Dense tubular systems are used for…

storage site for ionized calcium which is released into cytoplasm upon activation

The three stages for PRIMARY HEMOSTASIS are…

1. adhesion

2. activation

3. aggregation

Platelets normally do not interact with other cells (due to prostacyclin, NO, and ADPase). The damaged vessels expose flowing blood to subendothelial connective tissue composed to adhesive molecules. The two things I need to focus on are…

vWf and collagen fibers

What is the major receptor for VWF?

GPIb

What is the major receptor for fibrinogen?

GPIIb

What is the major receptor for Collagen?

GPIa (and also GPVI, GPIIb, and GPIV)

Platelet activator refers to adhesion, shape change, secretion, stickiness and aggregation. This is…

self-perpetuating and irreversible

What are the two strong agonists that stimulate and activate platelets?

Thrombin and collagen

Adhesion of platelets to collagen fibers via vWf triggers what?

Shape change/activation

What shape do inert platelets turn into once activated?

From disc shaped to sticky spheres with spiny projections (pseudopods)

Explain platelet aggregation

Newly arriving platelets flowing into the bleeding tissue, adhere to the tissue, become activated by contact with agonists, such as TXA2 and ADP, and products from damaged tissue`

What is the primary structure formed during primary hemostatis?

The platelet plug

Why does Aspirin have an effect on Platelet activation?

It is an antithrombotic agent that inhibits the production of TXA2

And what is TXA2 again?

Agonist that activates platelets

What does Aspirin cause?

• moderate prolongation of bleeding time

• Moderate inhibition of platelet aggregation

What does the activated platelet membrane provide for secondary hemostasis?

The phospholipid surface

These are regulatory factors:

• endothelial layer limits platelet contacts with collagen

• antagonists like NO are released

• flowing blood produces a “dilutional” effect on agonists

• intracellular calcium is tightly regulated