Coagulation question

[Hemichordate]

Does heparin induce inhibition of just factors II and X, or does it inhibit II, VII, IX, X, XI, and XII?

Also, since heparin increases both PT and PTT, why is PTT preferred? Does heparin affect the intrinsic pathway more?

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[coolforschool]

Does heparin induce inhibition of just factors II and X, or does it inhibit II, VII, IX, X, XI, and XII?

Also, since heparin increases both PT and PTT, why is PTT preferred? Does heparin affect the intrinsic pathway more?

Goljan says antithrombin III affects 12, 11, 7, 10, 2 and 1, and he also says that PTT is preferred for heparin management because, like you said, it affects the intrinsic pathway more (12 and 11 vs. 7). I haven't really fact-checked. IMO, it's probably due to convention with warfarin having INR values for PT.

 

[Nukeleic]

When thinking about heparin you have to clarify whether you are talking about unfractionated heparin or LMWH. Unfractionated heparin is able to bind ATIII and inactivate Xa and also thrombin, while LMWH is only the pentamer of heparin and therefore is "too small" to allow ATIII to inactivate thrombin and therefore only inhibits Xa.

From this point you can understand why PTT monitoring is useful for unfractionated heparin, but has no role in monitoring LMWH therapy. The reason is because thrombin has a feedback mechanism to activate factors XI, VIII, V, XIII and I. Factors XI is part of the intrinsic and thus prolongs PTT.

At least this is how I think about it, correct me if I am wrong.

 

[MLT2MT2DO]

When thinking about heparin you have to clarify whether you are talking about unfractionated heparin or LMWH. Unfractionated heparin is able to bind ATIII and inactivate Xa and also thrombin, while LMWH is only the pentamer of heparin and therefore is "too small" to allow ATIII to inactivate thrombin and therefore only inhibits Xa.

From this point you can understand why PTT monitoring is useful for unfractionated heparin, but has no role in monitoring LMWH therapy. The reason is because thrombin has a feedback mechanism to activate factors XI, VIII, V, XIII and I. Factors XI is part of the intrinsic and thus prolongs PTT.

At least this is how I think about it, correct me if I am wrong.

That makes so much more sense, so AT3 doesn't actually directly affect 1,5,8,11 and 13 but do so through factor 2?

 

[jsp132]

AT3 inhibits the formation of thrombin but binding and inactivating (Factor 2) prothrombin, Factor 9 and factor 10,

and Heparin binds to AT3 and causes an allosteric change that ENHANCES the inhibition of thrombin formation

the positive feedback loop happens as thrombin is made it activates more Factor 5, 8 and 11

while factor 11 amplifies the production of activated factor 9

so yes seems like thats why it affects mainly the intrinsic pathway more 8,9, 11, and 12

 

[Hemichordate]

Where do you get inactivation of factor VIII?

In my FA, I have "Antithrombin inactivates factors II, VII, IX, X, XI, XII."

I know heparin inactivates thrombin (II) and X, since they mention that in the pharmacology section, but does heparin also knock out VII, IX, XI, and XII? Is the effect just not as big on those coagulation factors?

 

[ketosisevangelist]

There is a special place in hell for Hematologists.