Coagulation

Understanding the basic principles of how platelets, the coagulation cascade, and fibrinolysis operate is simple when you break it down, understand the players involved, and understand the terminology. Let’s get started!

There are three main steps to hemostasis (which literally means blood equilibrium, hemo = blood, stasis = equilibrium).

1. Primary hemostasis – Circulating platelets bind and aggregate to a damaged vessel wall and form a platelet plug.

2. Secondary hemostasis (aka coagulation) – A series of cascading reactions take place and the end product is a fibrin clot that is formed in cooperation with the platelets.

3. Fibrinolysis – The clot is broken down and dissolved and the damaged vessel returns to normal.

So first things first, let’s say you get a cut on your arm and it’s bleeding. This is going to create a break in your blood vessel wall that needs repair. The damaged vessel will get smaller (vasoconstriction) which will limit the amount of blood flow to the area and decrease the amount of blood lost. Circulating platelets will quickly activate and aggregate at the site of damage via a set of chemical reactions which we will get into shortly. These platelets will form a temporary plug but in order for it to be solid it needs some glue, something to bind the platelets together, which will be supplied via the coagulation cascade.

We’ll start with primary hemostasis and the basic concepts of how the platelet plug is formed.

Platelets are the true first responders in coagulation and start the whole process when a blood vessel is injured and collagen is exposed. Platelet binding and aggregation occur when platelet receptor glycoprotein 1b (GP1b) combined with von Willebrand factor (vWF) bind to exposed collagen. What is GP1b and von Willebrand factor? GP1b is a receptor on the platelet and von Willebrand factor is a protein released from endothelial cells when they are ruptured that will bind to collagen. Endothelial cells line the internal surface of the blood vessel wall.

Platelets need both GP1b and von Willebrand factor in order to bind to collagen. Without GP1b, the platelets can’t bind vWF. Without vWF, the platelets can’t bind collagen. Once bound, the platelets will release ADP, ATP, and other compounds from their granules which will cause surrounding platelets to undergo a shape change. This shape change changes the activity of the platelet receptor glycoprotein 2b/3a (GP2b/3a) and makes it available to bind fibrinogen (a lot more on fibrinogen later). Simply put, GP2b/3a is a fibrinogen receptor. Platelets will bind together through this platelet-fibrinogen bridge and aggregate together to form a plug.

This strategy is effective in the short term but in the long term, you need secondary hemostasis which brings in the coagulation cascade.

Perspective Note
Platelets are about 2.8 micrometers in diameter and more sophisticated than your car or computer. The normal mean platelet volume (MPV) is 10 femtoliters (fL), and in a normal individual 1uL of blood contains between 150,000 and 450,000 platelets. The average person has about 5 liters of blood in their body which is equal to 5 million microliters. That means the average person has between 750 billion and 2.25 trillion platelets in their bodies at all times! Platelet precursor cells are megakaryocytes which precursors are hematopoietic pluripotent stem cells.