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Old 05-05-2015
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Default How is thrombin time preserved in direct factor Xa inhibitors?

How can the "xabans" not effect the thrombin time?
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Old 05-05-2015
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Quote:
Originally Posted by zeeviq View Post
How can the "xabans" not effect the thrombin time?
Well, some do and some don't. No all xabans act at the same spot. The keys are:

1) Understand the coagulation cascade
2) Understand how the tests (TT, PT, PTT) are performed
3) Know where the drug in question acts


For #1, there is a chart in basically every review book out there.

For #2 - we get the TT by taking a plasma sample, adding a ton of thrombin (aka factor IIa), and measuring how long it takes to clot.

For #3, lets first look at rivaroxaban (Xarelto). This is a direct inhibitor of factor Xa, a factor that is actually upstream of thrombin itself. In fact, Xa and Va come together to actually make thrombin! In this case, if I add thrombin to a test tube of plasma, i'm already past the point in the cycle where the drug acts, so the blood will clot no matter how much rivaroxaban the patient had been taking.

Now lets consider dabigatran. This is a direct thrombin inhibitor. If I add thrombin to a test tube of this plasma, the blood will not clot unless I add so much that I overwhelm the inhibitor. With this drug, the thrombin time is definitely prolonged.

I think the key you were missing was that not all xabans act at the same point, so it can be a little confusing when trying to remember all their mechanisms. In general: a thrombin inhibitor will give you a prolonged TT; if the drug acts anywhere upstream of that, you'll get little or no effect on the TT.
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Quote:
Originally Posted by Young Doc View Post
Well, some do and some don't. No all xabans act at the same spot. The keys are:

1) Understand the coagulation cascade
2) Understand how the tests (TT, PT, PTT) are performed
3) Know where the drug in question acts


For #1, there is a chart in basically every review book out there.

For #2 - we get the TT by taking a plasma sample, adding a ton of thrombin (aka factor IIa), and measuring how long it takes to clot.

For #3, lets first look at rivaroxaban (Xarelto). This is a direct inhibitor of factor Xa, a factor that is actually upstream of thrombin itself. In fact, Xa and Va come together to actually make thrombin! In this case, if I add thrombin to a test tube of plasma, i'm already past the point in the cycle where the drug acts, so the blood will clot no matter how much rivaroxaban the patient had been taking.

Now lets consider dabigatran. This is a direct thrombin inhibitor. If I add thrombin to a test tube of this plasma, the blood will not clot unless I add so much that I overwhelm the inhibitor. With this drug, the thrombin time is definitely prolonged.

I think the key you were missing was that not all xabans act at the same point, so it can be a little confusing when trying to remember all their mechanisms. In general: a thrombin inhibitor will give you a prolonged TT; if the drug acts anywhere upstream of that, you'll get little or no effect on the TT.
Thanks young doc ,
I was actually going through a U World question that caught my attention . Question Id 2133 .They had mentioned that factor Xa inhibitors increase PT and PTT but have no effect on TT.My conclusion was also as above , as you had mentioned , that since thrombin time is calculated from the point of adding in external thrombin to the formation of clot so it bypasses the inhibited step.

1) Do heparin and warfarin also have no effect on TT as we are always adding thrombin in the lab .Thrombin time will only be altered if fibrinogen levels are altered .
2) all xabans are factor Xa inhibitors so how can the TT be variable for them ?
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Quote:
Originally Posted by zeeviq View Post
Thanks young doc ,
I was actually going through a U World question that caught my attention . Question Id 2133 .They had mentioned that factor Xa inhibitors increase PT and PTT but have no effect on TT.My conclusion was also as above , as you had mentioned , that since thrombin time is calculated from the point of adding in external thrombin to the formation of clot so it bypasses the inhibited step.

1) Do heparin and warfarin also have no effect on TT as we are always adding thrombin in the lab .Thrombin time will only be altered if fibrinogen levels are altered .
2) all xabans are factor Xa inhibitors so how can the TT be variable for them ?
1) Correct, though maybe with a testable caveat. Remember that heparin acts through anti-thrombin III, so theoretically this would increase the TT. However, in the lab they control for this by using a thrombin-like substance that isn't affected by ATIII/heparin.

2) You are correct, I mistyped above. What I meant was that people often confuse many of the newer anticoagulants and I commonly see people lumping dabigatran in with the Xa inhibitors by accident because the names sound similar. I thought this might have been another possible source of confusion.
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Good discussion there. So LMW heparin would also have no effect on TT ? Right? Since it only affects factor Xa
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Quote:
Originally Posted by Hassan8 View Post
Good discussion there. So LMW heparin would also have no effect on TT ? Right? Since it only affects factor Xa
That is correct.
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Right dude
From karnataka?
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