HIT (Heparin-Induced Thrombocytopenia)

[futuredoctor10]

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Heparin-induced thrombocytopenia can be caused by both "regular" heparin (unfractionated) or LMWH. However, there is an increased risk for HIT with use of unfractionated heparin. Correct?

Questions:

1) Why does heparin elevate the aPTT levels, yet LMWH does not prolong aPTT? [I feel like we learned the mechanism in MS2 but I don't remember]

2) For diagnosis of HIT, I assume the fall in platelet count will be at least 5 days after heparin is given in the question stem? I ask since let's say the platelet count dropped in the first day or two, this could be the normal fall in platelets that is sometimes seen (non-immune) which returns to normal thereafter.

Thanks!

 

[cbcb00]

1) Why does heparin elevate the aPTT levels, yet LMWH does not prolong aPTT? [I feel like we learned the mechanism in MS2 but I don't remember]

2) For diagnosis of HIT, I assume the fall in platelet count will be at least 5 days after heparin is given in the question stem? I ask since let's say the platelet count dropped in the first day or two, this could be the normal fall in platelets that is sometimes seen (non-immune) which returns to normal thereafter.

Thanks!

1) PTT levels inc when factors 12,11,9,8 (and to a certain extent, the common pathway) are dec/inactivated. Heparin works on antithrombin, which inactivates factors 2,7,9,10,11,12... hence why it affects the PTT. On the other hand, LMWH's like Lovenox (and drugs like Arixtra) work on factor 10 directly, and not factors 12/11/9/8... aka they don't change the PTT.

2)
a) You'll get significantly lower platelets (we're talking about <100k here)
b) time frame (4-5 days after heparin for immune-mediated, vs <4 days in non-immune mediated thrombocytopenia)
c) any mention of clotting

 

[arden]

Heparin-induced thrombocytopenia can be caused by both "regular" heparin (unfractionated) or LMWH. However, there is an increased risk for HIT with use of unfractionated heparin. Correct?

Questions:

1) Why does heparin elevate the aPTT levels, yet LMWH does not prolong aPTT? [I feel like we learned the mechanism in MS2 but I don't remember]

2) For diagnosis of HIT, I assume the fall in platelet count will be at least 5 days after heparin is given in the question stem? I ask since let's say the platelet count dropped in the first day or two, this could be the normal fall in platelets that is sometimes seen (non-immune) which returns to normal thereafter.

Thanks!

Unfractionated heparin works on both ATIII and Factor II, whereas LMWH only affects ATIII. This should answer your aPTT question.
As to the platelet count fall, you have to differentiate between HIT I and HIT II, the first one being a mild reaction with a moderate fall in platelet count on day 1 or 2 of administration (non-allergic) and the second one is the really bad kind with dramatic platelet fall on day 5 or so of 1st administration. Since this one is an immune-mediated reaction, it will show up much sooner on subsequent administration.

Hope this helps.

Oh, and in case of HIT I you don't really have to discontinue heparin use, platelets will be normal again after a few days.

 

[futuredoctor10]

Makes sense, thanks to you both. I learned about HIT type I clinically, but without calling it that: so I never realized it was actually a subtype of HIT. Thanks for the clarifications! That's why UWorld always calls it HIT type II in all of their questions, even though they never discuss the HIT type I !

I can imagine the test writers making a tricky question about HIT I, with a slight fall in platelets on day 2 after heparin was started...

 

[kaleerkalut]

1) PTT levels inc when factors 12,11,9,8 (and to a certain extent, the common pathway) are dec/inactivated. Heparin works on antithrombin, which inactivates factors 2,7,9,10,11,12... hence why it affects the PTT. On the other hand, LMWH's like Lovenox (and drugs like Arixtra) work on factor 10 directly, and not factors 12/11/9/8... aka they don't change the PTT.

2)
a) You'll get significantly lower platelets (we're talking about <100k here)
b) time frame (4-5 days after heparin for immune-mediated, vs <4 days in non-immune mediated thrombocytopenia)
c) any mention of clotting

What are you guys talking about? It's been a little while since being on Wards but I'm fairly certain you still have a prolonged aPTT with Lovenox? Factor X is the meeting point of the common pathway so anything that inhibits Xa is going to prolong aPTT (as well as PT actually). Can someone confirm or deny (with sources preferably)?

 

[arden]

What are you guys talking about? It's been a little while since being on Wards but I'm fairly certain you still have a prolonged aPTT with Lovenox? Factor X is the meeting point of the common pathway so anything that inhibits Xa is going to prolong aPTT (as well as PT actually). Can someone confirm or deny (with sources preferably)?

My bad, I wansn't very specific. LMWH does change aPTT somewhat but not significantly enough to infer any meaningful information. Thus, anti-Factor Xa should be used to monitor therapy if needed.

Here's the link to Mayo Textbook of Internal Medicine:
http://books.google.de/books?id=YJt...e&q=why aptt not changed in lmwh mayo&f=false

 

[cbcb00]

What are you guys talking about? It's been a little while since being on Wards but I'm fairly certain you still have a prolonged aPTT with Lovenox? Factor X is the meeting point of the common pathway so anything that inhibits Xa is going to prolong aPTT (as well as PT actually). Can someone confirm or deny (with sources preferably)?

I think Arden answered your question perfectly. If LMWH changed PTT significantly, the monitoring would be through that (as in the case of hep), and not factor X. I didn't mean to say that there are no changes at all in the PTT.... That's why I mentioned in the post that PTT will still be affected by inhibition of the common pathway, to a certain extent 🙂

 

[kaleerkalut]

I think Arden answered your question perfectly. If LMWH changed PTT significantly, the monitoring would be through that (as in the case of hep), and not factor X. I didn't mean to say that there are no changes at all in the PTT.... That's why I mentioned in the post that PTT will still be affected by inhibition of the common pathway, to a certain extent 🙂

But your post above does state that PTT is not affected by Lovenox. That was the point of confusion. Either way, I think this has been solved. Thanks to everyone for contributing.