Notes from the Video

What You're Going to Learn from This Video on Coagulation Cascades

What do you know about clotting cascades? 

Are they simple or complex? 

In my experience they have been brain busting.

Today I'm going to make them simple!

After this video and these notes you're going to be confident in primary and secondary hemostasis as well as fibrinolysis.

It's going to be awesome.

You can use this information to better understand your patients on the wards or to crush your exams...your pick!

Today we’re going to accomplish the following three goals:

1.  Understand primary hemostasis

2. Know Fibrin Formation and Clotting Cascades

3.  Understand Fibrinolysis

What is primary hemostasis?

Primary hemostasis is the first stage of the body's process to stop bleeding after injury. It involves the formation of a platelet plug at the site of injury to prevent further blood loss.

When a blood vessel is damaged, platelets in the blood stream are activated and adhere to the exposed collagen fibers in the damaged vessel wall. The adhered platelets become activated, change shape and release chemicals that attract and activate more platelets.

This process leads to the formation of a platelet plug that seals the damaged vessel and prevents further blood loss.

In addition to platelet activation and aggregation, primary hemostasis also involves vasoconstriction, which narrows the damaged vessel and reduces blood flow to the site of injury.

This process helps to further reduce blood loss and increase the concentration of clotting factors in the damaged area.

Primary hemostasis is an essential process for controlling bleeding and initiating the next stage of the clotting process, known as secondary hemostasis, which involves the formation of a fibrin clot to further stabilize the platelet plug.

What are the major factors involved in primary hemostasis?

Platelets: Platelets are small cell fragments that circulate in the blood and play a critical role in the formation of the initial platelet plug. When a blood vessel is damaged, platelets adhere to the exposed collagen fibers in the vessel wall and become activated.

Von Willebrand factor (vWF): vWF is a large protein that is produced by endothelial cells, which line the inside of blood vessels. vWF helps platelets adhere to the damaged vessel wall by binding to both the platelets and the exposed collagen fibers in the vessel wall.

Coagulation factors: Several coagulation factors, such as factor VIII and IX, are involved in the initial stages of primary hemostasis. These factors help to activate platelets and promote the formation of the platelet plug.

Endothelial cells: Endothelial cells play a critical role in regulating hemostasis by producing and releasing vWF, as well as other factors that can either promote or inhibit platelet activation and aggregation.

Vasoconstriction: Vasoconstriction, or the narrowing of the damaged blood vessel, is also an important factor in primary hemostasis. This process helps to reduce blood flow to the site of injury, which can further reduce blood loss and promote the formation of the platelet plug.

What are the coagulation pathways involved in the formation of fibrin?

Fibrin is formed in the coagulation process through a series of enzymatic reactions known as the coagulation cascade.

The coagulation cascade involves the activation and interaction of various coagulation factors, leading to the formation of a fibrin clot.

The coagulation cascade can be divided into two pathways: the extrinsic pathway and the intrinsic pathway. Both pathways ultimately converge at a common final pathway that leads to the formation of fibrin.

In the extrinsic pathway, the coagulation process is initiated by the release of tissue factor, which is exposed when the blood vessel wall is damaged. Tissue factor then binds to factor VII, which leads to the activation of factor X.

In the intrinsic pathway, the coagulation process is initiated by the activation of factor XII, which ultimately leads to the activation of factor X.

Once factor X is activated, it combines with factor V to form prothrombin activator. Prothrombin activator then cleaves prothrombin, a plasma protein produced in the liver, to form thrombin. Thrombin then cleaves fibrinogen, another plasma protein, to form fibrin monomers.

Fibrin monomers then polymerize to form fibrin strands, which form a mesh-like network that traps platelets, red blood cells, and other components of the blood to form a clot. The clot then stabilizes over time as additional coagulation factors and enzymes are activated, leading to the formation of cross-links between the fibrin strands.

What is Fibrinolysis?

Fibrinolysis is the natural process by which the body breaks down blood clots that are no longer needed.

Once a blood clot has served its purpose, such as by stopping bleeding at a site of injury, the body must dissolve the clot to restore normal blood flow and prevent ongoing clot formation.

The main component of a blood clot is a meshwork of protein fibers called fibrin, which forms the structural framework of the clot.

Fibrinolysis occurs when the body produces a series of enzymes called plasminogen activators, which convert the inactive protein plasminogen into its active form, plasmin. Plasmin then breaks down the fibrin meshwork, allowing the clot to dissolve.

Plasminogen activators can be produced by various cells in the body, including endothelial cells that line blood vessels, as well as platelets and leukocytes. These cells release plasminogen activators in response to signals such as increased blood flow, which can indicate that a clot is no longer needed.

In addition to plasminogen activators, the body also produces inhibitors of fibrinolysis, such as plasminogen activator inhibitor-1 (PAI-1), which help to prevent excessive breakdown of blood clots.

Fibrinolysis is an important process in maintaining normal blood flow and preventing the formation of harmful blood clots. However, if fibrinolysis is impaired, blood clots may persist and lead to serious health problems, such as deep vein thrombosis, pulmonary embolism, or stroke.

What are the major components of fibrinolysis?

Plasminogen: A protein that is present in the blood and circulates in an inactive form. Plasminogen is converted to its active form, plasmin, by plasminogen activators.

Plasmin: An enzyme that breaks down fibrin, the structural component of blood clots. Plasmin also degrades other clotting factors, such as fibrinogen, prothrombin, and factor V.

Plasminogen activators: Enzymes that convert plasminogen to plasmin. There are two main types of plasminogen activators: tissue plasminogen activator (tPA) and urokinase plasminogen activator (uPA).

Plasminogen activator inhibitors: Proteins that regulate the activity of plasminogen activators by inhibiting their function. The main plasminogen activator inhibitor is called plasminogen activator inhibitor-1 (PAI-1).

Fibrin degradation products: Fragments of fibrin that are produced during the breakdown of blood clots. These fragments can circulate in the blood and be detected as markers of fibrinolysis.