Blood clotting

Where it happens

Blood clotting begins at the site of a damaged blood vessel, wherever platelets in the blood come into contact with the wound. It happens in the blood plasma, using clotting factors that circulate in the blood ready to act.

The reactions are confined to the damaged area because the trigger is contact between platelets and the rough, torn surface of the vessel wall or the exposed tissue around it. Intact vessels have a smooth inner lining, so platelets flow past without sticking and the plasma proteins stay in their inactive forms.

Clotting therefore happens only where blood meets tissue that it does not normally touch, which is why blood flowing inside a healthy vessel stays liquid while blood leaking from a cut solidifies within minutes.

Inputs and outputs

• Input: platelets, cell fragments produced in the bone marrow, which stick to the wound and release clotting substances.
• Input: prothrombin, an inactive plasma protein made in the liver and circulating in the blood.
• Input: fibrinogen, a soluble plasma protein also made in the liver.
• Input: calcium ions and vitamin K, both needed for the conversion of prothrombin into thrombin.
• Output: thrombin, the active enzyme formed from prothrombin at the wound site.
• Output: insoluble fibrin threads, formed from fibrinogen by the action of thrombin.
• Output: a clot, a mesh of fibrin holding trapped red blood cells and platelets, which dries into a scab.

The steps

1. A blood vessel is damaged and blood begins to leak out; platelets in the escaping blood touch the rough edge of the wound.
2. The platelets become sticky, clump together at the site and release substances that trigger the clotting process. This platelet plug slows the bleeding straight away.
3. The released substances, together with calcium ions, convert the inactive plasma protein prothrombin into the active enzyme thrombin.
4. Thrombin acts as a catalyst on the soluble protein fibrinogen, dissolved in the plasma, converting it into insoluble fibrin.
5. The fibrin molecules join end to end into long threads that stretch across the wound and form a fine mesh.
6. Red blood cells and platelets flowing past are trapped in the mesh, so the clot grows until the opening in the vessel is sealed.
7. The clot contracts and dries at the surface of the skin to form a scab, which stays in place while new tissue grows underneath and repairs the damage.

Why it matters and how it is controlled

Blood clotting stops excessive loss of blood from a wound and, once dried, forms a scab that protects the wound while it heals. The clot also acts as a barrier that helps prevent pathogens from entering the body through the damaged skin.

The process is controlled by keeping its key proteins inactive until they are needed. Prothrombin and fibrinogen travel in the plasma in soluble, inactive forms, and only the substances released by platelets at a wound can start the conversion of prothrombin into thrombin.

Because thrombin is an enzyme, a small amount converts a large quantity of fibrinogen, so the response is fast once triggered. Calcium ions and vitamin K are both required for the reaction, which is why a diet lacking vitamin K slows clotting.

Two consequences follow when control fails. If the clotting factors are missing or faulty, as in the inherited condition haemophilia, wounds bleed for much longer than usual.

If a clot forms inside an undamaged vessel, it can block the flow of blood; a blockage in a coronary artery is one cause of a heart attack. Exam questions use both cases to test whether you understand that clotting must happen quickly at a wound and not at all inside a healthy vessel.

How it is examined

You may be asked to describe the sequence from platelets to fibrin formation, to explain why fibrinogen must be converted to fibrin rather than clotting directly, or to explain why blood clotting is important as a defence mechanism against pathogens.

Structured questions often present the clotting sequence as an incomplete flow chart with boxes for prothrombin, thrombin, fibrinogen and fibrin, and ask you to fill in the missing names or to state which arrow represents an enzyme-catalysed reaction. A second common format gives a short case: a person whose blood takes a long time to clot, or whose diet lacks vitamin K, and asks you to suggest a reason using the steps of the process.

Essay prompts on the defence mechanisms of the body expect blood clotting to be given as the first line of defence, described in order and with the correct names of the plasma proteins, before phagocytosis and antibody production are discussed.

Common misconceptions

Worked exam-style question

Question. Diagram Y shows the sequence of events after a person cuts a finger. Stage 1: platelets gather at the cut.

Stage 2: substance P is converted into enzyme Q. Stage 3: enzyme Q converts protein R into threads S.

(a) Name P, Q, R and S. (b) Explain why R is soluble while S is insoluble, and why this difference is important.

(c) A patient's blood clots much more slowly than usual. Suggest one reason, referring to the sequence in the diagram.

Model answer. (a) P is prothrombin, Q is thrombin, R is fibrinogen and S is fibrin. (b) R, fibrinogen, is a soluble plasma protein, so it stays dissolved and can circulate in the blood without blocking vessels.

Thrombin converts it into insoluble fibrin threads, which form a mesh across the wound and trap red blood cells to make a solid clot. If fibrinogen were insoluble it would clot inside healthy vessels; if fibrin were soluble it could not seal the wound.

(c) The patient may lack vitamin K or calcium ions, both needed to convert prothrombin into thrombin, so less thrombin forms and fibrin is produced slowly. Alternatively, a low platelet count means fewer clotting substances are released at the wound to start the sequence.

Source:SRC-DSKP-EN

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