Difference Between Intrinsic and Extrinsic Pathways in Blood Clotting

Main Difference – Intrinsic vs Extrinsic Pathways in Blood Clotting

Damages (trauma) to blood vessels cause bleeding. The bodily processes that prevent bleeding can be categorized into two mechanisms: primary hemostasis and secondary hemostasis. Vasoconstriction and the formation of platelet plug are the two processes of primary hemostasis. The formation of a blood clot is the secondary hemostasis process that prevents bleeding in advance. The clot formation is facilitated by a group of proteins known as clotting factors. The activation of clotting factors occurs through a clotting cascade. Intrinsic and extrinsic pathways are the two separate pathways that lead to the formation of a blood clot. The main difference between intrinsic and extrinsic pathways in blood clotting is that intrinsic pathway is activated by a trauma inside the vascular system whereas extrinsic pathway is activated by external trauma.

Key Areas Covered

1. What is Intrinsic Pathway
       – Definition, Activation, Mechanism
2. What is Extrinsic Pathway
      – Definition, Activation, Mechanism
3. What are the Similarities Between Intrinsic and Extrinsic Pathway in Blood Clotting
     – Outline of Common Features
4. What is the Difference Between Intrinsic and Extrinsic Pathway in Blood Clotting 
     – Comparison of Key Differences

Key Terms: Clotting Factors, Blood Clotting, Extrinsic Pathway, Intrinsic Pathway, Platelets, Trauma

What is Intrinsic Pathway

Intrinsic pathway refers to multiple cascades of protein interactions activated by a trauma inside the blood vessels. It is also activated by platelets, exposed endothelium, or collagen. Generally, intrinsic pathway takes time to form a blood clot. The proteins involved in the formation of the blood clot are known as clotting factors. They are designated by I-XIII. The activation mechanism of these factors is known as the clotting cascade. The clotting factors involved in the intrinsic pathway are factors VIII, IX, XI, and XII. The clotting factors involved in both intrinsic and extrinsic pathways are shown in figure 1.

Figure 1: Clotting Factors

The intrinsic pathway is activated by the binding of factor XII to a negatively-charged foreign surface that is exposed to blood. This sequentially activates factors IX, X, and XI, further activating the factor II that converts prothrombin to thrombin. Thrombin converts fibrinogen to fibrin. Platelets are trapped inside a fibrin mesh, forming a blood clot.

What is Extrinsic Pathway

Extrinsic pathway refers tomultiple cascades of protein interactions activated by damaged external surfaces. Factor III and thromboplastin are involved in the extrinsic pathway. The extrinsic pathway is shorter than the intrinsic pathway, and it is quicker than the intrinsic pathway. The process of blood clotting is shown in figure 2.

Figure 2: Blood Clotting

Thromboplastin is a tissue factor (TF) that is not exposed to the blood under normal conditions. But under vascular or endothelial cell injury, the exposure of thromboplastin activates factor VIIa and phospholipids to be converted into factor IX. Finally, factor X is activated by the factor Xa from the extrinsic pathway.

Similarities Between Intrinsic and Extrinsic Pathway

• Intrinsic and extrinsic pathway are two types of pathways involved in the formation of blood clot.
• Both intrinsic and extrinsic pathways belong to secondary hemostasis mechanisms.
• Both intrinsic and extrinsic pathways are involved in the formation of prothrombin activator and factor X.
• Both intrinsic and extrinsic pathway end up in the common pathway.

Difference Between Intrinsic and Extrinsic Pathway in Blood Clotting

Definition

Intrinsic Pathway: Intrinsic pathway refers to multiple cascades of protein interactions activated by a trauma inside blood vessels.

Extrinsic Pathway: Extrinsic pathway refers to multiple cascades of protein interactions activated by damaged external surfaces.

Activation

Intrinsic Pathway: Intrinsic pathway is activated by internal trauma.

Extrinsic Pathway: Extrinsic pathway is activated by external trauma.

Clotting Factors

Intrinsic Pathway: Factors VIII, IX, XI, and XII are involved in the intrinsic pathway.

Extrinsic Pathway: Factor VII is involved in the extrinsic pathway.

Efficiency

Intrinsic Pathway: Intrinsic pathway is slow.

Extrinsic Pathway: Extrinsic pathways is fast.

Time Taken for the Initiation of the Pathway

Intrinsic Pathway: Intrinsic pathway takes about 15-20 seconds for the initiation of blood clotting.

Extrinsic Pathway: Extrinsic pathway takes about 2-6 minutes for the initiation of blood clotting.

Significance

Intrinsic Pathway: Intrinsic pathway requires ionized calcium for the activation of factor IX by factor IXa.

Extrinsic Pathway: Extrinsic pathway requires both calcium and tissue factor for the activation of factor IX by factor VIIa.

Conclusion

Intrinsic and extrinsic pathway are two separate pathways involved in the formation of a blood clot during a damage to a blood vessel. The intrinsic pathway is activated by a trauma inside blood vessels. The extrinsic pathway is activated by a trauma to an external surface of the body. The main difference between intrinsic and extrinsic pathway in blood clotting is their mechanism of activation/

Reference:

1. “Thrombus Formation III–Activation of Coagulation Cascade.” The Internet Stroke Center, Available here.

Image Courtesy:

1. ” Clotting Cascade” By Jng46 – Own work (CC BY-SA 4.0) via Commons Wikimedia
2. “1909 Blood Clotting” By OpenStax College – Anatomy & Physiology, Connexions Web site, Jun 19, 2013 (CC BY 3.0) via Commons Wikimedia