Physiology chapters
Platelets, haemostasis and clotting
How bleeding is stopped in four steps (vessel spasm, platelet plug, clot and later clot breakdown), the features of platelets, the intrinsic, extrinsic and common clotting pathways, natural anticoagulants, and the tests and disorders exams use.
- Haemostasis has four steps: vascular spasm, platelet plug, blood clot (coagulation), then fibrous organisation or dissolution.
- Platelets adhere via von Willebrand factor, activate (release ADP, thromboxane A2) and aggregate; normal count 150,000–400,000/µL, lifespan 8–12 days.
- The extrinsic pathway starts with tissue factor + factor VII (tested by PT); the intrinsic pathway with factor XII (tested by APTT); both meet at factor X to make thrombin and fibrin.
On this page
Overview
Haemostasis means stopping bleeding. When a vessel is cut, four things happen in order:
- Vascular spasm (the vessel constricts).
- Platelet plug formation.
- Blood clot formation (coagulation).
- Growth of fibrous tissue into the clot, or dissolving of the clot (fibrinolysis).
The body also keeps clotting in check, so that clots form only where needed.
Step 1: vascular spasm
The damaged vessel wall contracts immediately. This is caused by local reflexes, nerve signals and chemicals from platelets (especially thromboxane A2 and serotonin). It reduces blood loss for minutes to hours.
Platelets
- Small fragments (about 1–4 µm) of large marrow cells called megakaryocytes.
- No nucleus, but they contain actin and myosin, mitochondria, enzymes, and granules.
- Normal count: about 150,000–400,000 per µL.
- Lifespan: about 8–12 days; removed mainly by macrophages in the spleen.
- Production is controlled by thrombopoietin from the liver.
Step 2: the platelet plug
- Adhesion: platelets stick to exposed collagen in the damaged wall, through von Willebrand factor (binding the platelet receptor glycoprotein Ib).
- Activation: platelets swell, put out projections, and release ADP, thromboxane A2, serotonin and other factors.
- Aggregation: ADP and thromboxane A2 activate nearby platelets, which stick to each other via glycoprotein IIb/IIIa and fibrinogen bridges. A loose plug forms within seconds.
The intact endothelium releases prostacyclin and nitric oxide, which stop platelets sticking to healthy vessel walls.
Aspirin irreversibly blocks cyclo-oxygenase in platelets, so they make less thromboxane A2. Because platelets have no nucleus, they cannot make new enzyme, so the effect lasts for the platelet's life (about a week).
Step 3: coagulation
The clot is a mesh of fibrin threads that traps blood cells and platelets.
Clotting factors
| Number | Name |
|---|---|
| I | Fibrinogen |
| II | Prothrombin |
| III | Tissue factor (tissue thromboplastin) |
| IV | Calcium |
| V | Proaccelerin (labile factor) |
| VII | Proconvertin (stable factor) |
| VIII | Antihaemophilic factor |
| IX | Christmas factor |
| X | Stuart-Prower factor |
| XI | Plasma thromboplastin antecedent |
| XII | Hageman factor |
| XIII | Fibrin-stabilising factor |
There is no factor VI. Most factors are made in the liver.
The extrinsic pathway
Starts when blood meets tissue factor from damaged tissue outside the vessel. Tissue factor combines with factor VII and calcium to activate factor X. It is fast (seconds).
The intrinsic pathway
Starts when factor XII contacts exposed collagen or a foreign surface (such as glass). It activates XI → IX; IX with VIII, calcium and platelet phospholipid activates factor X. It is slower (minutes).
The common pathway
Activated factor X (with factor V, calcium and phospholipid) forms prothrombin activator, which converts:
Prothrombin (II) → thrombin, then thrombin converts fibrinogen (I) → fibrin.
Factor XIII cross-links the fibrin to make the clot strong. Thrombin also activates more factors (V, VIII, XI, XIII) and platelets: positive feedback.
Thrombin is the key enzyme: it turns fibrinogen into fibrin and drives the cascade forward.
Calcium is needed in almost every step. Blood is kept unclotted in test tubes by removing calcium (citrate, EDTA, oxalate).
Vitamin K
Factors II, VII, IX and X (and the natural anticoagulants protein C and S) need vitamin K for their final activation in the liver. Warfarin blocks vitamin K.
A widely used memory aid for the vitamin K-dependent factors: "1972": factors 10, 9, 7, 2.
Natural anticoagulants
- Smooth endothelium and its glycocalyx.
- Thrombomodulin on endothelium binds thrombin and activates protein C, which (with protein S) inactivates factors V and VIII.
- Antithrombin III: inactivates thrombin and factor X; heparin greatly increases its effect.
- Tissue factor pathway inhibitor.
Step 4: fibrinolysis
Within days, the clot is dissolved by plasmin, made from plasminogen. Plasminogen is activated by tissue plasminogen activator (tPA) from damaged endothelium (and by urokinase). Plasmin breaks fibrin into fibrin degradation products, including D-dimer.
Drugs such as alteplase (a tPA) and streptokinase are used to dissolve clots in stroke or heart attack.
Tests of haemostasis
| Test | Measures | Prolonged in |
|---|---|---|
| Platelet count | Number of platelets | Thrombocytopenia |
| Bleeding time (older test) | Platelet plug formation | Platelet disorders, von Willebrand disease, aspirin |
| Prothrombin time (PT) / INR | Extrinsic and common pathways (VII, X, V, II, fibrinogen) | Warfarin, vitamin K deficiency, liver disease |
| APTT | Intrinsic and common pathways (XII, XI, IX, VIII, X, V, II) | Heparin, haemophilia A and B |
Warfarin is monitored by PT/INR; unfractionated heparin by APTT.
Clinical relevance
Haemophilia
How it happens: X-linked recessive deficiency of factor VIII (haemophilia A) or factor IX (haemophilia B, Christmas disease); affects mainly males.
What you see: bleeding into joints and muscles, long APTT, normal PT and normal platelet count.
Von Willebrand disease
How it happens: deficiency of von Willebrand factor, the commonest inherited bleeding disorder. VWF also carries factor VIII, so factor VIII may be low.
What you see: mucosal bleeding (nose, gums, heavy periods); long bleeding time.
Vitamin K deficiency
How it happens: newborns (hence vitamin K at birth), malabsorption, obstructive jaundice, antibiotics, warfarin.
What you see: bleeding with a long PT.
Thrombocytopenia
How it happens: low platelet production or increased destruction (for example immune thrombocytopenia, dengue).
What you see: petechiae and bruising; serious bleeding risk when counts fall very low.
Expect: the four steps of haemostasis, platelet count and lifespan, the roles of von Willebrand factor, ADP and thromboxane A2, aspirin's action, the intrinsic, extrinsic and common pathways, vitamin K-dependent factors, which test reflects which pathway, natural anticoagulants, fibrinolysis, and the lab picture of haemophilia.
Quick revision
- Steps: vascular spasm, platelet plug, clot, fibrinolysis.
- Platelets: 150,000–400,000/µL; 8–12 days; from megakaryocytes.
- Adhesion: vWF; aggregation: GPIIb/IIIa, ADP, thromboxane A2.
- Extrinsic: tissue factor + VII (PT). Intrinsic: XII, XI, IX, VIII (APTT). Common: X, V, II, I.
- Vitamin K: II, VII, IX, X, protein C and S.
- Plasmin dissolves fibrin; tPA activates plasminogen.
- Haemophilia: long APTT, normal PT.
Written by The House Job from standard physiology references (Guyton and Hall Textbook of Medical Physiology; BRS Physiology).
FAQ
What are the steps of haemostasis?
Vascular spasm, formation of a platelet plug, blood coagulation, and finally fibrous organisation or dissolving of the clot.
Which clotting factors depend on vitamin K?
Factors II, VII, IX and X, and the anticoagulant proteins C and S.
Which test monitors warfarin?
The prothrombin time, reported as the INR.
What is the defect in haemophilia A?
A deficiency of clotting factor VIII.