Introduction:
Blood clotting, or coagulation, is the natural process that prevents excessive bleeding when a blood vessel is injured. Normally, blood flows freely inside vessels, but when exposed to air or damage occurs, it thickens to form a gel-like clot. This clot acts like a plug, sealing the wound and stopping further loss of blood.
The gel portion, known as the blood clot, is made of protein threads called fibrin, which trap blood cells. The clear liquid left behind is the serum, which is plasma without clotting proteins.
Clotting is a highly controlled series of chemical reactions involving various clotting factors, calcium ions (Ca²⁺), enzymes from the liver, and molecules released by platelets or damaged tissues.
The Three Stages of Blood Clotting:
Clot formation happens in three major steps:
- Formation of Prothrombinase – via the extrinsic or intrinsic pathways.
- Conversion of Prothrombin to Thrombin – catalyzed by prothrombinase.
- Formation of Fibrin Threads – thrombin converts soluble fibrinogen into insoluble fibrin, forming the final clot.
1. The Extrinsic Pathway:
This is the faster pathway, occurring within seconds after severe injury.
- It starts when tissue factor (TF), also called thromboplastin, leaks from damaged tissues into the bloodstream.
- In the presence of calcium ions, TF activates Factor X.
- Activated Factor X combines with Factor V and calcium to form prothrombinase — the enzyme that triggers clot formation.
2. The Intrinsic Pathway:
This pathway is slower but more detailed. It is triggered when blood comes into contact with damaged endothelium or collagen fibers.
- Platelets release phospholipids that start a chain of enzyme activations.
- Factor XII gets activated, which leads to the activation of Factor X.
- Like in the extrinsic pathway, Factor X and Factor V combine to form prothrombinase.
Both pathways finally merge into the common pathway.
3. The Common Pathway:
This is where both intrinsic and extrinsic pathways meet:
- Prothrombinase converts prothrombin (from the liver) into thrombin.
- Thrombin then converts fibrinogen (soluble) into fibrin (insoluble).
- Factor XIII strengthens these fibrin threads into a stable, durable clot.
Positive Feedback Loops:
- Thrombin accelerates its own production by activating Factor V.
- It also activates platelets, reinforcing the clotting process.
Clot Retraction and Repair:
Once formed, the clot shrinks — a process known as clot retraction.
- Platelets pull on the fibrin threads, drawing the damaged vessel edges closer together.
- This helps reduce bleeding and allows tissue repair.
- Fibroblasts and endothelial cells later rebuild the vessel wall permanently.
Role of Vitamin K in Clotting:
Vitamin K is essential for producing several clotting factors in the liver.
- It is fat-soluble and mainly produced by gut bacteria.
- Deficiency may cause uncontrolled bleeding due to poor clot formation.
- People with bile flow disorders or poor fat absorption are at higher risk.
Homeostatic Control of Clotting:
The body continuously prevents unwanted clot formation through a balance system:
- Fibrinolytic System: dissolves small or old clots after healing (fibrinolysis).
- Plasminogen, trapped in the clot, is activated to plasmin, which digests fibrin and other clotting proteins.
- Thrombin and tissue plasminogen activator (t-PA) are key to this process.
- Prostacyclin (from vessel walls) prevents excessive platelet sticking.
Natural anticoagulants like antithrombin, heparin, and activated protein C (APC) further prevent abnormal clotting.
Intravascular Clotting (Thrombosis):
Sometimes, clots form inside blood vessels without injury — this is called thrombosis.
- Causes: Atherosclerosis, slow blood flow, or vessel trauma.
- The formed clot is a thrombus; if it dislodges, it becomes an embolus.
- When an embolus blocks a vital artery (like in the lungs), it causes embolism, which can be life-threatening.
Summary of Clotting Factors:
| Factor Number | Name | Source / Function |
|---|---|---|
| I | Fibrinogen | Converted to fibrin by thrombin |
| II | Prothrombin | Precursor of thrombin |
| III | Tissue Factor (TF) | Triggers extrinsic pathway |
| IV | Calcium ions (Ca²⁺) | Essential cofactor |
| V | Proaccelerin | Combines with X to form prothrombinase |
| VIII | Antihemophilic Factor | Deficiency causes hemophilia A |
| IX | Christmas Factor | Part of intrinsic pathway |
| X | Stuart Factor | Common pathway enzyme |
| XIII | Fibrin Stabilizing Factor | Strengthens fibrin mesh |
Detailed Notes:
For pdf style full-color notes, open the complete study material below: