Platelet plug formation (primary hemostasis)

Definitions & Key takeaways

Platelet plug formation, also known as primary hemostasis, is the first step of hemostasis and is the process where a platelet plug forms to prevent further loss of blood from a damaged vessel. It is divided into five stages: endothelial injury, exposure, adhesion, activation, and aggregation. After the platelet plug is formed, it is not a strong enough barrier to stop the bleeding completely, it is further reinforced by secondary hemostasis, which is the process by which a protein called fibrin is used to create a more stable clot, also called clot retraction.

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Introduction0:00–1:02

Platelet plug formation, also called primary hemostasis, is the first of two steps needed for hemostasis. Hemostasis is how the body prevents blood loss a blood vessel is injured and broken.
Without hemostasis even a minor injury would be life-threatening - imagine dying from a nosebleed! During primary hemostasis, platelets clump up together and form a plug around the site of injury.
Then in the second stage, called secondary hemostasis, the platelet plug is reinforced by a protein mesh made up of fibrin.
You can think of it like a brick wall where the platelets make up the bricks and the fibrin makes up the mortar that goes between the bricks.
So going back to primary hemostasis, the clumping up of platelets - this step can be further divided into five steps: endothelial injury, exposure, adhesion, activation, and aggregation.

Case Study1:02–1:50

Let's imagine that you accidentally slice a tiny artery in your finger while cutting fruit, ouch! When this happens, the knife cuts several layers of the artery.
The innermost layer of the artery is the endothelium, and it’s made up of endothelial cells. Just outside of this layer are several layers of smooth muscle cells, which control the size of the lumen, or the inner diameter of the vessel by contraction and relaxation.
Outside of the smooth muscle there’s a layer of protein - specifically elastic fibers which give the blood vessel the ability to expand and contract.
Outside of the elastic fibers, there’s connective tissue made up of collagen, which is the major structural protein in humans.
This fibrous layer protects the vessel and anchors it to the surrounding tissues. So, the first thing that happens when the knife cuts your finger is endothelial injury.

Endothelial Injury1:50–2:36

When that happens, nerves that are attached to endothelial cells and the smooth muscle cells detect the injury and triggers a reflexive contraction of the smooth muscles near the injury site called vascular spasm.
This makes the vessel more narrow to reduce blood flow and ultimately decrease blood loss through the damaged artery. Now, endothelial cells normally secrete nitric oxide and prostaglandins into the blood which cause nearby smooth muscles to relax.
When there’s endothelial injury, secretion of nitric oxide and prostaglandins decreases, and the endothelial cells secrete a protein called endothelin instead, which causes the smooth muscles to contract.

Exposure2:36–2:52

The second step is exposure - that’s because damage to the endothelial cells exposes the collagen that is below them. And damaged endothelial cells release a protein called Von Willebrand's factor that binds to this exposed collagen.

Adhesion2:52–3:15

The third step is adhesion. Platelets, which are small fragments of larger cells called megakaryocytes, continuously circulate in the blood.
When endothelial cells are damaged, platelets come in contact with the Von-Willebrand factor bound to collagen. And platelets have a surface protein called GP1B that allows them to bind to the Von Willebrand factor proteins.

Activation3:15–5:00

The fourth step is activation. When platelets bind to Von Willebrand factor via GP1B, the platelet gets “activated” which means that it does a few things.
First, the platelet changes shape and its membrane forms tentacle like arms allowing it to grab onto other platelets. Second, platelets release more Von Willebrand factor, as well as serotonin, a tiny molecule that attracts more platelets to the area, and calcium, which is useful in secondary hemostasis.
Platelets also release adenosine diphosphate or ADP and thromboxane A2. These two molecules are secreted into the blood and activates other platelets that haven’t bound to Von Willebrand factor.
So as more and more platelets bind, there’s a snowball effect, and soon a ton of platelets are activated. It’s a positive feedback loop.
However, we don’t want all of our platelets to be used up just because we got a tiny cut on our finger, so the positive feedback loop is limited to the injury site.
The way that works is that prostaglandin and nitric oxide secreted by undamaged endothelial cells binds to platelets and keeps them from getting activated.
So we have this tug-of-war between prostaglandin and nitric oxide which are platelet inhibitors on one side, and ADP and thromboxane A2 which are platelet activators on the other.
Finally, when ADP and thromboxane A 2 binds to platelets, they express a new surface protein called GPIIB/IIIA - a bit like unlocking a new level in a game.
Once GPIIB/IIIA is expressed on the surface of the platelets, they’re considered fully activated. The fifth and final step is aggregation.

Aggregation5:00–5:56

Now, the ADP and thromboxane cause platelets to stick to collagen and the cause free floating platelets to express GPIIB/IIIA.
GPIIB/IIIA binds to fibrinogen which is a circulating blood protein, that acts like a little pair of handcuffs that links two platelets together.
Now each platelet have multiple GPIIB/IIIA receptors so they can bind to multiple other platelets with fibrinogen. As a result, platelets on the collagen can attach to fibrinogen, and that same fibrinogen can be bound by platelets floating in the blood.
This allows platelets to rapidly aggregate at the site of injury, and form a platelet plug that can help stop the bleeding.
During secondary hemostasis, fibrinogen gets cleaved into fibrin and these fibrin forms a protein mesh, kind of like a giant net that covers the platelet plug and keeps it together.
Alright, as a quick recap, primary hemostasis is the first step of hemostasis and is the process where a platelet plug forms to prevent further loss of blood from a damaged vessel.

Review5:56–6:17

Primary hemostasis is divided into five into distinct stages: endothelial injury, exposure, adhesion, activation, and aggregation.