First, a quick review of how a blood clot is formed
Here’s how you make a clot:Â
- Constrict the affected blood vessel
- Form a platelet plug
- Form fibrin (using the coagulation cascade) to seal up the platelet plugÂ
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?).
The two main coagulation lab tests
There are two main tests for evaluating the cascade: one for the extrinsic arm (the PT/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 PT/INR
The prothrombin time (PT) is performed by adding thromboplastin to the patient’s plasma, and seeing how long it takes to make fibrin (as soon as you see the first strands of fibrin form, the test is over, and you measure the result in seconds.
Thromboplastin contains a tissue-factor-like substance, and therefore it just measures the extrinsic pathway. The annoying thing about thromboplastin is that its strength varies considerably from manufacturer to manufacturer. So the PT done at one hospital (using manufacturer A’s thromboplastin) will be significantly different than the PT done at another hospital (using manufacturer B’s thromboplastin). Dumb.
To deal with this annoying issue, someone figured out how to make some mathematical calculations that take into account each manufacturer’s thromboplastin strength. Now, you just do your PT assay, add on those mathematical calculations, and you wind up with something called the International Normalized Ratio (INR). This means that you can do the PT with anybody’s thromboplastin, and you’ll wind up with a result (the INR) that removes that variability. Super important.Â
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. You have to add in a little “contact factor” like kaolin to activate XI to XIa – but other than that, that’s it!
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.
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!
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..
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: https://www.pathologystudent.com/?p=2305
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?
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.
thank u prof ur awesome in explaining things!!!thank u !!
Just to remember ,why it is called intrinsic and extrinsic pathways?
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).
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
Hi Dr.i want to ensure of (Bleeding time) just for platelet function, count and blood vessels also. Is this right?
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.
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.
Ah, I suppose that does sense, especially in light of their respective reference ranges. Thanks for the explanation!
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