Q. How come the PT and PTT are not increased in TTP and HUS? You have clots all over, so why don’t the coag tests go up like they do in DIC?
A. Great question! Bear with me…lots of acronyms coming up.
In disseminated intravascular coagulation (DIC), the coagulation system is activated (for many different possible reasons). The patient makes clots (consisting of platelets sealed up with fibrin) all over the place – and the prothrombin time (PT) and partial thromboplastin time (PTT) go up because the patient is using up all his/her coagulation factors! The platelet count goes down too, due to consumption.
In thrombotic thrombocytopenic purpura (TTP) and hemolytic-uremic syndrome (HUS), you’re right – there are clots all over. However, these clots aren’t really the same kind of clots that you see in DIC. In TTP and HUS, the problem is that platelets get caught in long von Willebrand factor multimers, and you get platelet clumping. The “clots” are really platelet clumps – not traditional clots (coated with fibrin). So the PT and PTT don’t go up much if at all. Â A fine point, perhaps, but a potentially important one when you have a patient that has a microangiopathic hemolytic anemia (MAHA) and you’re trying to figure out what to do. Most patients with TTP should get plasma exchange – and fast! So if you have a patient with MAHA, thrombocytopenia, and normal (or barely elevated) PT/PTT Â – start thinking TTP/HUS.
You’ve got a really outstanding webpage, Sword lily I actually detected it via yahoo and google.
This is something I keep studying and having to re-learn every time I encounter it. Thanks so much for the direct and accessible explanation! Your site has been so helpful– I wish I’d known about it day 1 of med school 🙂
Awesome explanation, thanks!
thanx… its really helpful…. grt explanation….
Perhaps unlikely, but is it possible that there would be a factor VIII deficiency if there is dysfunctional vWF leading to an elevated PTT?
Yes – absolutely! If von Willebrand factor is decreased, factor VIII (which is normally carried by vWF) may also decrease (which would elevate the PTT).
In dic all coagulation factors r consumed that’s y dic is also known as consumption coagulopathy – raised PT PTT.. & in Itp the clots are made up of platelets -NORMAL PT PTT..
Exactly! (You meant TTP, I’m assuming, not ITP – in which there is a decrease in platelets and no coag abnormalities.)
thanks for such a nice explanation
thanks for the explanation:)
since the platelets are activated though, why does it not trigger the coagulation cascade? (i understand that platelet aggregation can activate thrombin which activates a lot of the other factors within the cascade.)
does that mean that in TTP, there’s no vessel damage (hence factor VIIa+TF is not present)? thank you:)
Hi Qin –
Sorry it took me so long to get back to you! I didn’t see your comment – it got buried somehow on my comment list.
Whew that’s a good question. I don’t have a good answer for that. I haven’t seen that particular point discussed. It may have to do with the fact that the platelet aggregates are really bound to von Willebrand factor (not to the subendothelium) and thus the typical events in the coagulation cascade do not occur. It’s like the von Willebrand factor fragments are sticky strings just hanging out into the bloodstream, and platelets get stuck to them. It’s not really the same process as a vessel wall getting damaged, and platelets first adhesing, then releasing their granules, then aggregating. I’m not even sure the extent to which the platelets release their granules in TTP!
So I don’t have a great answer for you – only a theory that since the platelets are binding to vWF multimers (and not to the subendothelium), the typical activation of coagulation does not occur.
I hope that helps a bit!
Kristine
Hi I came to this site with the same question as Qin but I think my roommate just answered it for me.
I think this is because In TTP you have activation of primary hemolysis. In TTP secondary to decreased ADAMTS13 which allows excessively large vWF you have platelet adhesion and aggregation. However because there is no inherent endothelial damage the tissue thromboplastin and subendothelial collagen are not exposed to the phospholipid surface of the platelets and thus secondary hemostatsis and coagulation activation is not achieved.
However I still dont understand why in HUS you dont have a large activation of the coagulation cascade because I think this disorder is defined by endothelial damage.
Hi Tayor –
Yes – I totally agree, both with your reasoning on TTP and also your question on HUS. It is true that in the thrombotic microangiopathies the main problem is not activation of the coagulation cascade (the INR and PTT are not prolonged!). However, in the case of HUS, you’re right – the toxins in E. coli (which is what most cases are caused by) initiate endothelial damage. Soooo….I haven’t seen a good explanation rectifying these two concepts. I will keep looking though – it bugs me.
Awesome answer…thank u
just wanted to thank you for writing a blog targeted to medical student level. a lot of other resources are either too high or too low, and every time i find myself googling the random questions i think of while studying, i usually am directed here. you have an awesome way of explaining things. Thank you!
Thanks so much, Tina!! So glad you’re finding something useful 🙂