Haemostasis and Blood Clotting

 

Haemostasis and Blood Clotting

Introduction

Haemostasis is the physiological process that prevents excessive bleeding when a blood vessel is injured. It involves a complex interaction between blood vessels, platelets, and clotting factors. The process ensures that blood remains fluid within the vessels while rapidly forming a clot at sites of vascular injury.

Phases of Haemostasis

Haemostasis occurs in three main stages:

1. Vascular Spasm (Vasoconstriction)

When a blood vessel is injured, it undergoes immediate constriction to reduce blood flow. This response is triggered by neural reflexes and the release of vasoactive substances such as endothelin from endothelial cells. The spasm lasts for a short duration but is critical for limiting blood loss.

2. Platelet Plug Formation (Primary Haemostasis)

Platelets adhere to the exposed collagen fibers at the injury site via von Willebrand factor (vWF). Activated platelets release substances such as thromboxane A2, ADP, and serotonin, which further recruit and activate more platelets. The aggregated platelets form a temporary "platelet plug" that covers the damaged vessel wall.

3. Blood Coagulation (Secondary Haemostasis)

This phase involves the conversion of soluble fibrinogen into an insoluble fibrin clot through a cascade of enzymatic reactions. Clot formation stabilizes the platelet plug and effectively seals the vessel.

Mechanism of Blood Clotting (Coagulation Cascade)

Blood clotting, or coagulation, is a complex process involving a cascade of enzymatic reactions that convert soluble plasma proteins into an insoluble fibrin clot. This process occurs in multiple steps, ensuring precise control and regulation. The coagulation cascade consists of three major pathways: Intrinsic Pathway, Extrinsic Pathway, and Common Pathway.

1. Intrinsic Pathway (Contact Activation Pathway)

This pathway is activated when blood comes into contact with a negatively charged surface, such as exposed collagen within damaged blood vessels. It involves a series of clotting factors that sequentially activate one another. The process is slower but provides a more sustained response.

Steps in the Intrinsic Pathway

1. Activation of Factor XII (Hageman Factor) – Contact with collagen activates Factor XII.
2. Factor XIIa activates Factor XI – Factor XI is converted to its active form (Factor XIa).
3. Factor XIa activates Factor IX – In the presence of calcium ions (Ca²⁺), Factor XIa converts Factor IX to its active form (Factor IXa).
4. Factor IXa, along with Factor VIIIa, activates Factor X – This step is assisted by calcium ions and a phospholipid surface.
5. The pathway then merges into the common pathway at the activation of Factor X.

 

2. Extrinsic Pathway (Tissue Factor Pathway)

This pathway is initiated by external trauma that damages blood vessels and releases Tissue Factor (TF) (also called Factor III) from damaged endothelial cells. It is a rapid process and is the primary mechanism for initiating clot formation.

Steps in the Extrinsic Pathway

1. Tissue Factor (TF) binds to Factor VII – This complex activates Factor VII to Factor VIIa.
2. TF-Factor VIIa complex activates Factor X – This step is dependent on calcium ions.
3. The pathway converges into the common pathway at Factor X activation.

3. Common Pathway

Once Factor X is activated (by either the intrinsic or extrinsic pathway), it initiates the final stages of coagulation, leading to clot formation.

Steps in the Common Pathway

1. Activation of Prothrombin (Factor II) to Thrombin

Factor Xa, in combination with Factor Va, converts prothrombin (inactive) into thrombin (active). This reaction requires calcium ions and a phospholipid surface provided by platelets.

2. Conversion of Fibrinogen to Fibrin

Thrombin cleaves fibrinogen (Factor I) into fibrin monomers. These monomers spontaneously polymerize to form a soft fibrin clot.

3. Stabilization of the Fibrin Clot

Factor XIII (Fibrin-Stabilizing Factor) is activated by thrombin. Activated Factor XIII strengthens and cross-links the fibrin mesh, forming a stable clot that seals the wound.

Regulation of Blood Clotting

Since coagulation must be tightly regulated to prevent excessive clot formation, several mechanisms control the process:

Antithrombin III – Inhibits thrombin and other clotting factors to prevent excessive clot formation.

Protein C and Protein S – Inactivate Factors Va and VIIIa, downregulating the clotting process.

Tissue Plasminogen Activator (tPA) – Converts plasminogen into plasmin, which degrades fibrin and dissolves the clot (fibrinolysis).

Fibrinolysis: Dissolution of the Clot

After wound healing, the clot must be removed to restore normal blood flow. This process is called fibrinolysis and occurs as follows:

1. Plasminogen is converted to Plasmin – Tissue Plasminogen Activator (tPA) activates plasminogen into plasmin.
2. Plasmin breaks down Fibrin – The fibrin network is degraded into smaller fragments (fibrin degradation products).
3. Restoration of Blood Flow – As the clot dissolves, normal circulation resumes.

Clinical Significance

Haemophilia – A genetic disorder where clotting factors (VIII or IX) are deficient, leading to excessive bleeding.

Thrombosis – Formation of unwanted clots inside blood vessels, which can lead to heart attacks or strokes.

Vitamin K Deficiency – Vitamin K is necessary for the synthesis of clotting factors (II, VII, IX, and X). A deficiency impairs clotting.

References

1. Guyton, A. C., & Hall, J. E. (2020). Textbook of Medical Physiology. Elsevier.
2. Tortora, G. J., & Derrickson, B. (2018). Principles of Anatomy and Physiology. Wiley.
3. Alberts, B., Johnson, A., Lewis, J., et al. (2014). Molecular Biology of the Cell. Garland Science.
4. Ross, M. H., & Pawlina, W. (2018). Histology: A Text and Atlas. Lippincott Williams & Wilkins.