There are two models used to explain what is thought to happen during haemostasis – the classical model and the cell based model. The classical model is the one we’re all more familar with and is more intuitive, though doesn’t explain the whole picture.

Classical model


Platelets are crucial to clot formation. They are small disc shaped cell fragments without nuclei. They are formed from fragmentation of megakaryocytes in the bone marrow and circulation, with a life span of 5-9 days.

  1. Activation: Exposure to subendothelial connective tissue (contains collagen, tissue factor and von Willebrand factor), exposure to thrombin, release of thromboxane A2 and non-physiological flow conditions or stasis e.g. arterial stenosis, mechanical heart valves.
  2. Shape change: Changes in the cytoskeleton cause the platelet to become stellate in shape.
  3. Thromboxane A2 synthesis: The arachidonic acid pathway is initiated, causing synthesis of thromboxane A2 via cyclooxygenase 1 from arachidonic acid.
  4. Platelet adhesion and aggregation: Platelets clump together using fibrin and von Willebrand factor as connecting agents.This is mediated through the abundant Glycoprotein IIb/IIIa receptor, which is a calcium dependant receptor for fibrin and von Willebrand factor.

The platelet plug must be enmeshed by fibrin to form a stable haemostatic clot.

Coagulation cascade


Two arms (intrinsic and extrinsic) converge into the final common pathway resulting in conversion of fibrinogen to fibrin.


Limitation of coagulation to site of injury crucial to avoid systemic coagulation and clotting complications.

Protein C is the body’s main source of anticoagulant activity. It works predominantly on factor V which helps activate factor X. This is particularly relevant in congenital abnormalities e.g. factor V Leiden – protein C doesn’t work on an abnormal factor V, therefore there is uncontrolled coagulation and systemic clotting problems.

Prostacyclin is from the prostaglandin family and is secreted by vessel walls. It inhibits platelet aggregation by increased cyclic AMP which inhibits vesicle release of substances like thromboxane A2 and therefore prevents activation of the platelet. It also promotes vasodilatation, encouraging favourable flow conditions.

Antithrombin III binds to thrombin creating an inactive complex, and also has some inhibitory effect on factors IX, X, XI and XIII.

Plasminogen activation breaks down fibrin into soluble fibrin degradation products which have no haemostatic effect.

Cell based model

Very complex model used to explain inaccuracies of the classical model. For example life threatening haemorrhage does not occur in the absence of factor XII.

The sum of three processes:

  1. Initiation
  2. Amplification
  3. Propagation

It is thought to occur on the cell surface rather than as a cascade.