There is a fine line between maintaining blood fluidity and excessive haemorrhage. Haemostasis is a physiological response of the body to damage or injury to vascular structures. When preparing for exams like NEET PG, INI-CET, and USMLE, medical aspirants should learn about haemostasis, as it forms an important part of the syllabus. 

This guide presents a coherent and palatable description of haemostasis, including its phases, regulation, clinical importance, and typical disorders.

What is Haemostasis?

Haemostasis is a well-regulated physiological process by which blood is maintained in a liquid state inside the vessels, yet arrests bleeding at the site of vascular injury by forming a haemostatic clot.

It involves a coordinated series of events that facilitates:

• Coagulation of damaged blood vessels,
• Avoiding blood loss in excess,
• Keeping the fluidity of blood in undamaged vessels
  

Despite its protective functions, haemostasis may fail to regulate itself, and the resulting dysregulation may manifest as thrombosis (excessive clotting) or haemorrhage (excessive bleeding). Therefore, medical professionals need to be aware of both physiology and pathology.

What are the Stages and Their Mechanisms in Haemostasis?

Usually, blood vessels are lined by a smooth, non-thrombogenic endothelium. Haemostasis is a precisely orchestrated process that involves platelets, clotting (coagulation) factors, the endothelium of blood vessels, and the fibrinolytic system. 

The general sequence of events of haemostasis at a site of vascular injury is as follows:

1. Arteriolar Vasoconstriction

It occurs immediately after vascular injury and significantly reduces the blood flow to the injured site. This is mediated by reflex neurogenic mechanisms and enhanced by the local secretion of factors such as endothelin (a potent endothelium-derived vasoconstrictor). This vasoconstriction is transient, and bleeding may resume if platelet and coagulation factor activation is not sustained.

2. Primary Haemostatic Plug

Platelets play an essential role in haemostasis. Primary haemostasis refers to the formation of a platelet plug at the site of injury. It occurs immediately, within seconds of injury, and is responsible for the cessation of bleeding from microvasculature. 

Primary haemostasis involves three key steps, which are:

• Platelet Adhesion and Shape Change

i) The initial step is the adhesion of platelets to subendothelial structures at the site of injury. 

ii) The link between the receptor sites (GpIb-IX, which is an integrin) on the surface of the platelet with exposed subendothelial collagen is brought out by an adhesion glycoprotein called von Willebrand factor. 

iii) Following adhesion, platelets change their shape from round to spherical smooth discs to spiky “sea urchins” with protrusions, thereby markedly increasing the surface area. 

iv) This change is accompanied by glycoprotein IIb/IIIa, which increases its affinity for fibrinogen.

v) Translocation of negatively charged phospholipids to the surface of platelets. These negatively charged phospholipids on the surface bind calcium and serve as nucleation sites for the formation of coagulation factor complexes.

• Platelet Secretion, Activation, and Recruitment

Soon after platelets undergo a shape change, they release the contents of their granules, collectively known as platelet activation. Several factors, including the coagulation factor thrombin and ADP, trigger platelet activation.

i) Thrombin activates platelets by switching on a special type of G-protein-coupled receptor [protease-activated receptor (PAR)].

ii) Platelet activation and the release of ADP lead to additional rounds of platelet activation, a phenomenon known as recruitment. This process contains pro-aggregatory substances, such as ADP, serotonin (5-hydroxytryptamine), fibrinogen, and von Willebrand factor (vWF), that recruit additional platelets. 

iv) Calcium is also released and is required for coagulation.

• Platelet Aggregation

The secreted products of platelets recruit additional platelets and cause platelet aggregation through the receptor sites (Gp IIb-IIIa). This process is mediated by fibrinogen, which acts as an intercellular bridge between adjacent platelets. 

Inherited deficiency of Gpllb-Illa produces a bleeding disorder called Glanzmann thrombasthenia. Activated platelets also produce the prostaglandin called thromboxane A (TxA), which induces strong aggregation of platelets.

These clumps of platelets so formed quickly (within 3 to 7 minutes) stop bleeding from the site of injury and are known as primary haemostatic plugs. The process of primary haemostatic plug formation is referred to as primary haemostasis.

3. Secondary Haemostatic Plug

It is characterised by the deposition of fibrin at the site of vascular injury. This process typically takes between 3 and 10 minutes.

• Exposure of tissue factor at the site of injury. Tissue factor is a membrane-bound procoagulant glycoprotein. It is usually expressed by subendothelial cells in the vessel wall, namely smooth muscle cells and fibroblasts. Tissue factor binds and activates factor VII. 
• This, in turn, activates a cascade of reactions that generate thrombin. 
• Thrombin is a potent activator of platelets and causes additional platelet aggregation (of the primary haemostatic plug) at the site of injury. The initial platelet aggregation is reversible. 

However, concurrent activation of thrombin stabilises the platelet plug by causing further activation and aggregation, which in turn promotes irreversible contraction of platelets. Platelet contraction is dependent on the cytoskeleton of platelets:

• Thrombin cleaves circulating fibrinogen into insoluble fibrin, thereby forming a fibrin meshwork at the site of vascular injury. The platelets contract to create an irreversibly fused mass. 
• The fibrin formed from fibrinogen cements the platelets and produces a definitive secondary haemostatic plug. 
• Red blood cells and leukocytes also become trapped in the fibrin meshwork and are found in haemostatic plugs. 

The process of conversion of the initial temporary primary haemostatic (platelet) plug into a permanent secondary haemostatic plug is known as secondary haemostasis. It consolidates the initial platelet plug.

The solid permanent plug so formed prevents any further haemorrhage, and the haemostatic plugs/clots thus formed are confined to the site of injury by the fibrinolytic system. Subsequently, vascular repair is accomplished by thrombolysis and recanalisation of the occluded site.

Pathway	Trigger	Key Lab Test
Intrinsic	Contact with negatively charged surfaces	aPTT
Extrinsic	Tissue factor from injured cells	PT/INR
Common	Factor X activation leads to thrombin and fibrin	PT & aPTT

4. Clot Stabilisation and Resorption

Polymerised fibrin and platelet aggregates contract and form a solid, permanent plug. This prevents further haemorrhage. Simultaneously, counter-regulatory mechanisms are activated [e.g., tissue plasminogen activator (t-PA) released from endothelial cells], which limit clotting at the site of injury and eventually lead to resorption and tissue repair.

Failure of the haemostatic system to restore an injured vessel causes bleeding; inability to maintain the fluidity of blood results in thrombosis. 

What is the Clinical Importance of Haemostasis?

A well-regulated haemostasis system prevents both bleeding and unwanted clot formation. Let’s explore its clinical implications:

1. Bleeding Disorders (Hypocoagulable States)
2. Disorders of Primary Haemostasis

Vessel Wall Abnormalities:

• Congenital, e.g., Ehlers-Danlos syndrome
• Acquired, e.g., Henoch-Schönlein purpura

Platelet Abnormalities:

i) Quantitative: Thrombocytopenia (e.g., ITP, drug-induced, congenital)

ii) Qualitative: Platelet function disorders:

• Inherited, e.g., Glanzmann thrombasthenia, Wiskott-Aldrich syndrome, Bernard-Soulier syndrome
• Acquired, e.g., uremia, drugs
  

Caused by defects in haemostasis components:

Disorder	Defect	Clinical Features
Haemophilia A/B	Factor VIII / IX deficiency	Hemarthrosis, deep bleeding
von Willebrand disease	vWF deficiency	Mucosal bleeding, prolonged bleeding
Thrombocytopenia	Low platelets	Petechiae, purpura, gum bleeding
Liver disease	Impaired clotting factor synthesis	Generalised bleeding tendencies

Key Test: Bleeding time, PT, aPTT, platelet count

2. Disorders of the Coagulation System (Disorders of Secondary Haemostasis)

• Congenital: Haemophilia A, B; von Willebrand disease; other coagulation factor deficiencies (XI, VII, II, V, X)
• Acquired: Vitamin K deficiency, liver disease, disseminated intravascular coagulation

2. Thrombotic Disorders

1. Inherited:

• Deficiency of Antithrombotic Factors: Antithrombin III deficiency, protein C deficiency, protein S deficiency
• Increased Prothrombotic Factors: Activated protein C (APC) resistance (Factor V mutation/factor V Leiden), Prothrombin (G20210A mutation)

2. Acquired: Fibrinolytic system defects

Clinical Signs:

• DVT (leg swelling, pain)
• Pulmonary embolism (chest pain, dyspnea)
• Stroke (ischaemia in the brain)

FAQs About Haemostasis

1. What’s the difference between primary and secondary haemostasis?

Primary haemostasis is the formation of a platelet plug at the place of injury. Secondary haemostasis is the reinforcement of the plug by the clotting cascade, which forms a fibrin clot.

2. Which vitamin is crucial for haemostasis?

Vitamin K is essential in the synthesis of clotting factors II, VII, IX, and X. Lack of it poses a greater risk.

3. How do anticoagulants affect haemostasis?

They inhibit various points in the coagulation cascade:

• Heparin: Enhances antithrombin III (blocks thrombin and Xa).
• Warfarin: Inhibits vitamin K recycling.
• DOACs: Directly inhibit thrombin (dabigatran) or factor Xa (rivaroxaban).

4. What triggers pathological haemostasis?

Conditions, such as trauma, sepsis, cancer, or autoimmune disease, that result in too much or too little haemostasis may result in bleeding or thrombosis.

Conclusion

Haemostasis is the fundamental mechanism by which the body maintains internal stability by preventing blood loss and ensuring regular circulation. It involves an orchestrated sequence of activities, including vasoconstriction, platelet plug formation, coagulation, and fibrinolysis. It is essential to have a deeper understanding of these stages when trying to comprehend bleeding and clotting disorders, both clinically and during examinations.

For aspirants preparing for NEET PG, platforms like DocTutorials provide structured guidance, clinical insights, and high-yield content tailored to help them master essential topics. Whether you are reviewing mechanisms or working on challenging multiple-choice questions, understanding the concept of haemostasis will pay off both on the exam and in practice in the field.Check out our NEET PG study materials today!