Making a blood clot involves three steps:
1. blood vessel constriction
2. platelet plug formation, and
3. fibrin formation (also called coagulation).

There are lab tests that evaluate steps 2 and 3 (nobody talks much about poor step 1). Let’s look at the main tests that are used to evaluate step 3.

If you think back to the basics of the coagulation cascade, you might recall that there are two arms – an extrinsic arm and an intrinsic arm – which come together in the final common pathway, which ends up turning fibrinogen into fibrin. When somebody is bleeding, and you think it’s due to a coagulation problem (as opposed to a platelet problem), it’s helpful to know what part of the cascade is screwed up. That helps you figure out what’s wrong with the patient (is it hemophilia? or liver disease? or coumadin overdose?).

There are two main tests for evaluating the cascade: one for the extrinsic arm (the INR) and one for the intrinsic arm (the PTT). There are other tests too – but those will have to be for another post.

1. The INR

In the olden days, this test was called the prothrombin time (or PT), and it was extremely variable from lab to lab. Now, the lab applies a mathematical correction to the PT to make the results more consistent. The new name for the nice standardized PT is the INR, or “international normalized ratio.”

Whatever. What you do in this test is add thromboplastin (which acts like tissue factor, the thing that kicks off the coagulation cascade in vivo) to patient plasma, and wait to see how long it takes for fibrin to form. This test (for reasons we’ll have to discuss in another post, since we’ve limited this one to 400 words) measures the extrinsic pathway, which is that arm of the coagulation cascade that involves tissue factor, factor VII, and the final common pathway (X, V, II, and fibrinogen).

2. The PTT

The PTT, or partial thromboplastin time, is performed by adding just some phospholipid to the patient’s plasma and waiting to see how long it takes to form fibrin. It’s called the “partial thromboplastin” time because initially, it was found that by adding a part of thromboplastin to a test tube, you could activate fibrin formation. It turns out that the part of thromboplastin people were adding was just phospholipid, and that thromboplastin consists of both phospholipid and tissue factor. This test measures the intrinsic pathway, which is that arm of the cascade involving factors XI, IX, VIII and the final common pathway.

Whew. Okay, that was 431 words. Close enough.

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15 Responses to Coagulation tests in 400 words or less

  1. Stacey says:

    I am always in the continuing education cycle. Your site breaks things down to a no-nonsense to the point refreshingly blunt manner. Here’s to simplicity and getting to the point. (Can you tell I a coming up on a deadline : ) Thanks!

  2. Jenny says:

    Hey Professor Krafts! Just a question that I don’t understand though – in Von Willebrand Disease, aren’t the problem is just the vWF? Why actually APTT is prolonged but PT is normal? This is confusing..

  3. Kristine says:

    Good question! It turns out that von Willebrand factor is the carrier molecule for factor VIII. So if you have severe vWD, you can see a decrease in factor VIII (and a prolonged PTT). Nothing on the extrinsic side is affected though – so the PT/INR is normal. Here’s a post that talks a little about this: http://www.pathologystudent.com/?p=2305

  4. rajagopal t.v says:

    prof krafts i’ve a question
    in both intrinsic and extrinsic pathway tests we add thromboplastin? then how does it differ in measuring two different pathways?

  5. Kristine says:

    Hi Rajagopal –
    Good question! In the PT (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. So thromboplastin kicks off the extrinsic pathway (because it acts like tissue factor), and if you just add phospholipids, you’ll form fibrin, but without tissue factor around to activate the extrinsic pathway, you’ll make fibrin via the intrinsic pathway.

  6. rajagopal t.v says:

    thank u prof ur awesome in explaining things!!!thank u !!

  7. […] makes sense – because the two tests actually measure totally different things. We all know what the PTT measures: the intrinsic pathway (and final common pathway) of the coagulation cascade. That means factors […]

  8. Fadel says:

    Just to remember ,why it is called intrinsic and extrinsic pathways?

  9. Kristine says:

    The intrinsic pathway is named that way because everything you need to get it to run is already intrinsic to the blood (all the factors, phospholipids, calcium). The extrinsic pathway won’t get going unless you add something extrinsic to the blood (that something is tissue factor, which only becomes visible when you need to start making fibrin).

  10. frank forte says:

    really great . 400 words or less is just the right amount to tell if yu understand it .
    I have been in heme onc for 45= years and get a kick out of your Bites

  11. Mohamed Osman says:

    Hi Dr.i want to ensure of (Bleeding time) just for platelet function, count and blood vessels also. Is this right?

  12. Brian says:

    Thanks for the great explanation. A thought occurred to me, though. Perhaps I’m missing something simple, but when testing the INR, how do you know the intrinsic pathway isn’t also initiated since you have still added all of the necessary substances to start the PTT? In other words, how do you know you’re only testing the extrinsic pathway and not the intrinsic as well? Thanks in advance.

  13. Kristine says:

    Great question! I’ve never seen an explanation of this – but I think it’s because the extrinsic pathway is much quicker. It only takes about 12 seconds for the extrinsic pathway to make fibrin when you add thromboplastin (or tissue factor + phospholipid). But it takes about 30 seconds for the intrinsic pathway to make fibrin when you add phospholipid. So even though you’re adding phospholipid in the PT/INR, the test is terminated before the extrinsic pathway has a chance to kick in.

  14. Brian says:

    Ah, I suppose that does sense, especially in light of their respective reference ranges. Thanks for the explanation!

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