C3.2 Defense against disease

When a blood vessel is damaged, exposed collagen fibres activate circulating platelets, which adhere to the wound site. This is the first cellular event.

Simultaneously, damaged tissue cells release tissue factor (Factor III), which triggers the extrinsic clotting factor cascade. Activated platelets also contribute phospholipid surfaces that support this cascade.

The cascade culminates in the formation of thrombin, the enzyme responsible for the next critical conversion: $\text{Fibrinogen}\stackrel{\text{Thrombin}}{\to }\text{Fibrin}$

Insoluble fibrin threads then polymerise into a mesh that traps erythrocytes and platelets, forming the stable clot. The correct order is therefore: platelet adhesion → tissue factor release → thrombin production → fibrinogen → fibrin → mesh.

This corresponds to sequence 4 → 2 → 3 → 5 → 1.

The question tests knowledge of the correct chronological order of blood clotting steps. Identifying the first and last steps makes elimination straightforward.

Option 2 → 4 → 3 → 5 → 1 begins with tissue factor release before platelet adhesion to collagen. Platelet adhesion to exposed collagen is actually the first cellular response to vascular injury, so this order is incorrect.

This option places fibrin mesh formation (step 1) before fibrinogen conversion (step 5), which is biochemically impossible — fibrin must be formed before it can mesh.

This places thrombin production (3) before tissue factor release (2), but tissue factor is part of the cascade that ultimately generates thrombin, so thrombin cannot precede tissue factor.

4 → 2 → 3 → 5 → 1 is the only sequence where platelet adhesion initiates the process, tissue factor drives the cascade producing thrombin, which then converts fibrinogen to fibrin, completing the mesh.