Blood Coagulation Mechanism - 3 Stages of Clotting Cascade Explained | BS Zoology

By Momina Shehzadi | BS Zoology Graduate, Pakistan

In this article, we will learn Blood Coagulation - Hemostasis, Clotting Factors, Extrinsic and Intrinsic Pathways - in simple words with flow chart. This topic is very important for BS Zoology, Medical and Paramedical students .

Blood Coagulation - Hemostasis, Clotting Cascade and Disorders

Blood coagulation or blood clotting is the process by which blood changes from a liquid to a gel, forming a blood clot. It is a vital protective mechanism. Without clotting, we would bleed to death even from a small cut. But if blood clots inside blood vessels, it causes heart attack and stroke. So body maintains a perfect balance between clotting and anti-clotting.

For BS Zoology students, blood coagulation is one of the most important topics. It comes every year in final exam for 10 marks.

What is Hemostasis? - 3 Steps to Stop Bleeding

Hemostasis means prevention of blood loss. When a blood vessel is injured, hemostasis happens in 3 steps:

Step 1: Vasoconstriction

Immediately after injury, the damaged blood vessel constricts (becomes narrow). This reduces blood flow to injured area. This is temporary and lasts for few minutes.

Step 2: Platelet Plug Formation

Platelets are small cell fragments without nucleus. Normally they do not stick to vessel wall. But when vessel is injured, collagen under endothelium is exposed. Platelets stick to collagen with help of von Willebrand factor (vWF). Once stuck, platelets become activated and release ADP, Thromboxane A2, and serotonin. These chemicals attract more platelets. Many platelets clump together and form a temporary soft plug. This plug is called Platelet Plug. It can stop bleeding from small capillaries.

Step 3: Blood Coagulation - Formation of Fibrin Clot

Platelet plug is temporary and weak. To make it strong and stable, blood coagulation is needed. Coagulation converts soluble fibrinogen into insoluble fibrin threads. Fibrin threads form a mesh that traps RBCs and makes clot hard.

Clotting Factors - 13 Factors

There are 13 clotting factors, named by Roman numerals I to XIII. Most clotting factors are proteins made in liver.

-Factor I: Fibrinogen

-Factor II: Prothrombin

-Factor III:Tissue Thromboplastin or Tissue Factor

-Factor IV: Calcium ions (Ca2+)

-Factor VII, IX, X, II need Vitamin K: That is why Vitamin K deficiency causes bleeding disease. Vitamin K is needed for synthesis of these factors in liver.

- Factor VIII:Deficient in Hemophilia A

- Factor IX:Deficient in Hemophilia B

These factors are present in plasma in inactive form. They are activated one after another like a cascade, where one factor activates next.

3 Stages of Blood Coagulation - The Clotting Cascade

This is the most important part. Coagulation happens in 3 stages:

Stage 1: Formation of Prothrombin Activator - The Most Complex Stage

This stage has two separate pathways - Extrinsic Pathway and Intrinsic Pathway. Both lead to formation of Prothrombin Activator.

A) Extrinsic Pathway - Fast Pathway (Takes 15 seconds):

This pathway is called extrinsic because it is triggered by something outside blood. When tissue is injured outside vessel, damaged tissue releases Tissue Factor or Tissue Thromboplastin (Factor III). Factor III comes in contact with blood. Factor III + Factor VII + Calcium ions (Factor IV) together activate Factor X. This is very fast pathway, completes within 15 seconds after severe injury.

B) Intrinsic Pathway - Slow Pathway (Takes 1-6 minutes):

This pathway is called intrinsic because it is triggered by something inside blood itself. When blood vessel endothelium is damaged, blood comes in direct contact with collagen fibers. Collagen activates Factor XII. Then cascade starts: Factor XII activates Factor XI, Factor XI activates Factor IX. Factor IX needs Factor VIII to activate Factor X. This pathway is slow, takes 1 to 6 minutes. Hemophilia A is due to deficiency of Factor VIII, so intrinsic pathway is defective in hemophilia.

Both Pathways Merge: Whether extrinsic or intrinsic, both activate Factor X. Activated Factor X combines with Factor V, Calcium ions, and platelet phospholipids to form a complex called Prothrombin Activator. This complex is also called Prothrombinase. Prothrombin Activator is the key enzyme that starts next stage.

Stage 2: Prothrombin Converts to Thrombin - The Central Step

Prothrombin (Factor II) is a protein present in plasma in inactive form. It is made in liver with help of Vitamin K. Prothrombin Activator formed in Stage 1, in presence of Calcium ions, converts inactive Prothrombin into active Thrombin. Thrombin is a powerful enzyme. This is the central and most important step of clotting. Without thrombin, clot cannot form.

Stage 3: Fibrinogen Converts to Fibrin Clot - Final Clot Formation

Fibrinogen (Factor I) is a soluble protein present in plasma in large amount, about 300 mg/dl. Thrombin converts soluble Fibrinogen into insoluble Fibrin threads. Fibrin is sticky and forms long threads like mesh or net. This mesh traps Red Blood Cells, White Blood Cells and platelets. The trapped blood cells make clot red and solid. Initially fibrin threads are weak, but Factor XIII (Fibrin Stabilizing Factor) cross-links them and makes clot very strong and stable.

After Clot Formation - Clot Retraction and Fibrinolysis

After stable clot is formed, platelets inside clot contract. They contain contractile proteins actin and myosin like muscles. Contraction pulls wound edges together and squeezes serum out of clot. This is called Clot Retraction. It helps in wound healing.

Later, when wound is completely healed, clot is no longer needed. Then plasmin enzyme dissolves fibrin threads. This process of dissolving clot is called Fibrinolysis. Plasmin is formed from plasminogen. After fibrinolysis, blood vessel becomes open again and blood flow is normal.

Disorders of Blood Coagulation

1. Hemophilia A: This is X-linked recessive genetic disease, more common in males. Due to deficiency of Factor VIII. Patient bleeds for long time even after minor injury like tooth extraction. Treatment is Factor VIII injection.

2. Hemophilia B or Christmas Disease:

 Due to deficiency of Factor IX.

3. Vitamin K Deficiency:

 Vitamin K is needed for Factors II, VII, IX, X. Newborn babies have low Vitamin K, so they are given Vitamin K injection at birth to prevent hemorrhagic disease of newborn.

4. Thrombosis: When unwanted clot forms inside blood vessel, it blocks blood flow. If clot blocks coronary artery, it causes heart attack. If blocks brain artery, causes stroke.

5. Anticoagulants: Heparin and warfarin are medicines that prevent clotting. Heparin is given in hospital, warfarin is tablet.

Conclusion

Blood coagulation is a cascade mechanism where one factor activates next factor, amplifying signal. Remember 3 stages: 1) Formation of Prothrombin Activator via Extrinsic (Factor III, VII) and Intrinsic (Factor XII, XI, IX, VIII) pathways, 2) Prothrombin to Thrombin, 3) Fibrinogen to Fibrin clot. For exam, always draw flow chart and mention Vitamin K dependent factors and calcium role.

FAQs for Students

Q1: What are the 3 stages of blood coagulation?

Ans: Stage 1 Formation of Prothrombin Activator, Stage 2 Prothrombin converts to Thrombin, Stage 3 Fibrinogen converts to Fibrin Clot.

Q2: Which factors need Vitamin K?

Ans: Factor II Prothrombin, Factor VII, Factor IX and Factor X need Vitamin K for synthesis in liver. Vitamin K deficiency causes bleeding.

Q3: What is the difference between Extrinsic and Intrinsic Pathway?

Ans: Extrinsic pathway is fast, 15 seconds, triggered by Tissue Factor Factor III from outside blood. Intrinsic pathway is slow, 1 to 6 minutes, triggered by collagen inside blood activating Factor XII.

Q4: What is Hemophilia A and B?

Ans: Hemophilia A is due to deficiency of Factor VIII. Hemophilia B or Christmas Disease is due to deficiency of Factor IX. Both are X-linked recessive and more common in males.

Also Read: Blood Transfusion - Types and Compatibility Chart

Also Read: What is Rhogam Injection? - Prevention of Erythroblastosis Fetalis

Also Read: ABO Blood Group System - Complete Guide

Written by Momina Shehzadi, BS Zoology Graduate from Pakistan.