Prothrombin time versus APTT
The prothrombin time (PT) tests the extrinsic pathway, triggered by damaged vessel cells, and the activated partial thromboplastin time (APTT) tests the intrinsic pathway, triggered by exposed collagen.
Remember
A prolonged PT with a normal APTT points to the extrinsic pathway, as seen early in warfarin treatment when factor VII falls, while a prolonged APTT with a normal PT localises the problem to the intrinsic pathway.
Clotting ends in fibrin, threads of protein that cross-link to form a mesh. The mesh catches platelets and holds the blood clot together. The clotting cascade is the chain reaction of clotting factors (blood proteins) that produces fibrin, and it has two branches, or pathways, that lead to the same result.
The extrinsic pathway is triggered by thromboplastin (also called tissue factor), released from damaged endothelial cells, the cells lining the vessel wall. The word extrinsic means from outside, because the trigger comes from damaged tissue outside the blood itself. Its function is measured by the prothrombin time, which times how long a sample of plasma takes to clot once thromboplastin is added.
The intrinsic pathway is triggered by collagen exposed when a blood vessel is damaged. It is measured by the activated partial thromboplastin time.
The PT can also be reported as the international normalised ratio (INR), which compares the PT with a normal value. An INR of 1 is normal, and a higher INR means slower clotting, as in a patient taking warfarin. Warfarin is a vitamin K antagonist: it lowers the vitamin K-dependent clotting factors II, VII, IX and X. Factor VII, on the extrinsic pathway, has the shortest half-life of these (the time taken for half of it to be cleared), so it falls first and the PT lengthens early.
A prolonged PT with a normal APTT points to the extrinsic pathway, and a prolonged APTT with a normal PT points to the intrinsic pathway. If both are prolonged, think of the shared common pathway, where the two branches join and fibrinogen is turned into fibrin, or of several factors. A normal bleeding time, an older test of platelet aggregation (platelets clumping into a plug), argues against a platelet problem.
Key facts
- Prothrombin time (PT)
- follows the extrinsic pathway and is prolonged by warfarin.
- Activated partial thromboplastin time (APTT)
- follows the intrinsic pathway, triggered by exposed collagen, and can stay normal on warfarin.
- International normalised ratio (INR)
- the PT expressed as a ratio to a normal value, used to monitor warfarin.
- Early change on warfarin
- factor VII falls fastest, so the PT lengthens early.
- Isolated long APTT
- a prolonged APTT with a normal PT localises the problem to the intrinsic pathway.
- Prolonged PT with a normal APTT
- suggests factor VII deficiency, with common settings being early warfarin treatment, early vitamin K deficiency and early liver disease.
- Both times prolonged
- think of the shared common pathway or several factors.
Exam traps
- The APTT follows the intrinsic pathway and can stay normal even when the INR is high, so it is not the test used to monitor warfarin, which acts first on factor VII of the extrinsic pathway.
- A deficiency of factor VIII or factor IX prolongs the APTT while the PT stays normal, so it does not explain a prolonged PT with a normal APTT, which places the defect on the extrinsic side.
- The final common pathway, where fibrinogen is converted to fibrin, is shared by both branches, so a defect there is expected to prolong both the PT and the APTT and does not fit a prolonged APTT with a normal PT.
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