Q. I have a question about the coagulation lab tests. I saw that an increased PT would result from Coumadin and Heparin. Do these both work to activate ATIII and therefore effect the extrinsic pathway? I then saw that PTT can be increased as a result of heparin as well, so I am confused as to where heparin works and what effect is has on the coagulation cascade.

A. Great question! Although both Coumadin (warfarin) and heparin inhibit the coagulation cascade (and thus the formation of fibrin), they have different mechanisms of action.

Coumadin works by inhibiting the vitamin K dependent coagulation factors. Several factors in the cascade (II, VII, IX and X) need to be carboxylated in order to bind calcium (which is intimately involved in the cascade). The thing that performs the carboxylation is vitamin K; it goes from a reduced state to an oxidized state during carboxylation, and it is recycled back to its reduced state by an enzyme called vitamin K epoxide reductase. Coumadin inhibits this enzyme – so vitamin K can’t carboxylate the coagulation factors, which then are unable to bind calcium, and are rendered ineffective. Whew.

Heparin works in a totally different fashion. It works by binding to antithrombin III (ATIII), which as you will recall is a natural anticoagulant that acts on a bunch of different factors on both sides of the cascade, but seems to have more of an effect on the intrinsic arm than it does on the extrinsic arm of coagulation. Heparin binds to ATIII, causing a conformational change that activates ATIII and potentiates its action.

Back to the tests. Since both Coumadin and heparin affect factors on both sides of the coagulation pathway, giving either Coumadin or heparin should cause the prolongation of both the PT/INR and the PTT. However, the PT/INR is a better test for monitoring patients on Coumadin, and the PTT is a better test for monitoring patients on heparin, for the following reasons.

Coumadin affects all the vitamin K dependent coagulation factors. However, these factors have different half-lives. It turns out that of all the factors (II, VII, IX and X), factor VII has the shortest half-life. So if you give a patient Coumadin, the first factor to show a decrease in activity will be factor VII (the others will drop off too, but not until later on). When you give someone Coumadin, it’s important to go slow and only give as much as is necessary. So it’s best to monitor therapy by taking a look at the extrinsic pathway (using the PT/INR), since that’s the pathway that will be affected first. You wouldn’t want to wait until the PTT becomes prolonged before adjusting the patient’s dose, because by that time, the patient could be over-anticoagulated.

Heparin acts on a whole bunch of factors on both sides of the cascade – but it seems to have more profound effects of the factors of the intrinsic arm than those in the extrinsic arm. So if you were picking between ordering a PT/INR and a PTT, the PTT would be the more sensitive test to order.

 

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20 Responses to How do heparin and Coumadin affect the coagulation cascade?

  1. Eva says:

    Brilliant, thanks! I’ve been wondering about this for a while.

  2. Kristine says:

    Great! Glad to help.

  3. Stephen Garramone, M.D. says:

    OUTSTANDING!

  4. Julie says:

    Regards to this topic, why is it necessary to put a patient on Heparin before starting them on Coumadin??

  5. Kristine says:

    Great question! See this post, Question 4 (especially the last paragraph).

  6. jyoti baral says:

    very well explained….

  7. sheetal musmade says:

    Nice explaination . It realy helped me.

  8. Michael Z. Johny says:

    Great! Thanks so much for your simple but brilliant explanation …

  9. Heba says:

    wonderful post!!! answered my question in an easy way to rememberand also a wonderful site. thanks for making it easier

  10. Islam says:

    wonderful…thank you very much it helped me too much ask allah to help you in worldly life and afterlife

  11. mehdi says:

    so many many thanks. i did not find this question of mine in any other site but you. if you mind please put the reference too. thanks a lot

  12. Ledo says:

    Thanks!
    That is quite helpful.

  13. Veritas1 says:

    Very clear explanation. Thank you

  14. Connor says:

    Textbook quality explanation. Thank you.

  15. rachel says:

    Ahh. Thank you very much!!!

  16. Lizzy says:

    Extremely helpful. Thank you!!

  17. Katherine says:

    Very helpful! Thanks!

  18. Chief says:

    Amazing explanation. No other website teaches this interesting and important medical lesson. Not even uptodate or medscape. Thank you

  19. Carol says:

    Thanks…. Well explained

  20. Frank MD says:

    Succinctly explained.
    Excellent!
    Thank you so much!!

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