mymedschool.orgM08.04.003 Coagulation: General Concepts

Coagulation (hemostasis) is a tightly regulated balance between clot formation (to prevent bleeding) and fibrinolysis (to dissolve unnecessary clots). It involves vascular endothelium, platelets, and the coagulation cascade.

⚖️ Clotting = balance between thrombus formation and fibrinolysis.

I. Phases of Hemostasis

Stage	Main Components	Key Events
1. Vascular Phase	Endothelium, Endothelin-1	Vasoconstriction reduces blood flow.
2. Platelet Phase	Platelets, von Willebrand Factor (vWF)	Platelet adhesion → activation → aggregation.
3. Coagulation Phase	Coagulation factors (intrinsic & extrinsic pathways)	Fibrin mesh formation stabilizes the platelet plug.
4. Clot Retraction & Repair	Platelet actin, myosin, fibroblasts	Clot contracts and tissue repair begins.
5. Fibrinolysis	Plasmin, tPA	Breakdown of fibrin and restoration of normal flow.

II. Platelet Function and Disorders

Platelet Formation

Platelets are fragments of megakaryocytes in bone marrow.
Normal count: 150,000–400,000/mm³.

Steps in Platelet Plug Formation

Step	Process	Key Molecules
1. Adhesion	vWF binds to exposed collagen → platelets attach via GPIb	vWF, Collagen
2. Activation	Shape change & degranulation → release of ADP and TXA₂	ADP, Thromboxane A₂
3. Aggregation	Platelets link via fibrinogen and GPIIb/IIIa	Fibrinogen, GPIIb/IIIa

💊 Aspirin irreversibly inhibits cyclooxygenase, blocking TXA₂ and impairing platelet aggregation.

Platelet Granules

Alpha Granules	Dense Bodies
Fibrinogen, Fibronectin, Factor V, vWF, PDGF	ADP, Ca²⁺, Histamine, Serotonin, Epinephrine

Inherited Platelet Disorders

Disorder	Defect	Mechanism	Clinical Features
Bernard–Soulier Syndrome	GPIb–IX–V complex	↓ Platelet adhesion	Mucocutaneous bleeding in childhood
Glanzmann Thrombasthenia	GPIIb–IIIa complex	↓ Platelet aggregation	Prolonged bleeding time
von Willebrand Disease	vWF deficiency or dysfunction	↓ Platelet adhesion	Easy bruising, mucosal bleeding

III. Coagulation Cascade

Pathway	Trigger	Monitored By	Key Steps
Intrinsic Pathway	Contact with collagen (XII → XIIa)	aPTT (Heparin)	XII → XI → IX → VIII → X
Extrinsic Pathway	Tissue factor release	PT (Warfarin)	VII → X
Common Pathway	Convergence of intrinsic & extrinsic	—	X → V → II (Prothrombin → Thrombin) → I (Fibrinogen → Fibrin)

🧬 Calcium and phospholipid surfaces are essential cofactors in many steps.

Clinical Correlation

Drug	Mechanism	Monitoring Test
Warfarin	Inhibits vitamin K–K-dependent factor synthesis (II, VII, IX, X)	PT (Extrinsic)
Heparin	Activates antithrombin III → inhibits thrombin and Xa	aPTT (Intrinsic)

Key Points to Remember

Hemostasis balances clot formation and breakdown.
Platelet adhesion → activation → aggregation form the primary plug.
The coagulation cascade stabilizes the plug with fibrin.
vWF connects platelets to collagen and carries factor VIII.
Intrinsic = Heparin (PTT); Extrinsic = Warfarin (PT).

Learning Objective

By the end of this lesson, the student should be able to explain the phases of hemostasis, describe platelet function and key disorders, and distinguish intrinsic from extrinsic coagulation pathways, correlating them with clinical testing and drug therapy.