Coagulation questions seem to come up all the time! Here’s a good one from one of our readers.

Q. In both the PT and PTT we add thromboplastin, right? So how come the PT measures the extrinsic pathway and the PTT measures the intrinsic pathway?

A. This is a great question because it really gets at the underlying concepts of the PT (INR) and PTT. When I was a medical student, I never really thought about why the INR only measured the extrinsic pathway and the PTT measured only the intrinsic pathway. I just memorized the substance added to the test tube in each test, and the pathway the test measured. Later on, though, I realized I didn’t have a clue as to why the tests measured the pathways they did.

Before we get into the reasoning behind the tests, a quick correction is in order. We don’t add thromboplastin in both the INR and PTT. In the INR, you add thromboplastin, and in the PTT you add phospholipids (not thromboplastin). It turns out thromboplastin is a substance that contains both phospholipids AND a tissue-factor-like substance. That’s why they call the assay the “partial thromboplastin time” – because you only need to add part of the thromboplastin reagent (the phospholipid part) to get this test to run.

To understand why the PT measures just the extrinsic pathway and the PTT measures just the intrinsic pathway, you need to know what activates these pathways in the body. The extrinsic pathway is activated by tissue factor. The intrinsic pathway can be activated by a bunch of things, the most important of which is thrombin.

Why the INR measures the extrinsic pathway

To get blood in a test tube to form fibrin along the extrinsic pathway, you need to add some tissue-factor-like substance. Also, since you removed the platelets and calcium before running the test, you need to add those things back into the test tube (the coagulation system needs a phospholipid surface, normally provided by platelets, and calcium to run). Thromboplastin is a substance that contains both phospholipids and a tissue-factor-like substance. Add thromboplastin and some calcium, and the blood in the test tube will form fibrin via the extrinsic pathway.

Why the PTT measures intrinsic pathway

To get blood in a test tube to form fibrin along the intrinsic pathway, you don’t need to add any tissue-factor-like substance (if you do, the extrinsic pathway will be activated!). All you need to do is add back what you took out of the blood (phospholipids and calcium), as well as something like silica or kaolin to activate the intrinsic pathway (normally, thrombin does this job in vivo), and you’ll form fibrin along the intrinsic pathway. This is actually why the intrinsic pathway was named the way it was: everything you need to get the pathway to run is “intrinsic” to the blood. The extrinsic pathway requires something “extrinsic” to the blood (tissue factor) for it to run.

Bottom line

The INR activates the extrinsic pathway because in this test you add thromboplastin (which contains both a tissue-factor-like substance and phospholipids) to the test tube. The PTT activates the intrinsic pathway because in this test you add just phospholipids to the test tube – and without tissue factor around, fibrin is formed along the intrinsic pathway.