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Warfarin is said to change prothrombin time (PT) but not activated partial thromboplastin time (aPTT) (for practical purposes at least anyways, not really sure). But looking at the mechanism of action of warfarin, I don't see why that is.

Warfarin works by inhibiting vitamin K, or more specifically, vitamin K-mediated post-transnational modifications of certain clotting factors (X, IX, VII and II) which are important for the activity of said clotting factors. Warfarin affects factors in both the extrinsic and intrinsic pathway (and maybe a bit silly and irrelevant, but the same number of factors in each too; 3 by 3!). So, why is it that PT is affected by warfarin but aPTT isn't? I looked a lot and couldn't really find any satisfactory answer (there weren't many answers to begin with either). What I've found and have gotten from my professor are the following points:

  1. Warfarin's effect is more pronounced on PT because factor VII (the first factor in the extrinsic pathway) has the shortest half-life and is therefore the quickest to get depleted. But in that case, warfarin usually takes a few days to be considered effective enough to stop administering patients heparin with it; wouldn't all the affected factors be depleted enough by that time to also affect aPTT?
  2. Warfarin affects factor VII, which is the initiating factor (tissue factor aside) for the extrinsic pathway, which is why it affects PT more? Honestly I don't know how these tests work exactly so I'm not sure if this would matter. This was what my professor answered with when a student asked (or at least it's what I recall).
  • This doesn't answer your questions, but is an interesting complement to what you asked: medicalsciences.stackexchange.com/questions/23407/… – D.Tan May 28 at 16:28
  • Oh yeah I actually saw that too and bookmarked it. It was one of the “questions that might be similar to yours” thingy when I was typing this question. – Dahen May 28 at 16:31
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According to UpToDate:

At levels of therapeutic anticoagulation, VKAs (vitamin K antagonists) typically cause only mild prolongation (or do not prolong) the activated partial thromboplastin time (aPTT), and they do not prolong the anti-factor Xa activity level, a test typically used to measure the effect of heparin or direct oral factor Xa inhibitors

I was not able to find a mechanism for why VKAs might not prolong aPTT, but there is evidence to suggest that it can prolong aPTT, especially at higher doses and has an additive effect when administered with heparin.

As your question alluded to, factor VII has the shortest half-life (4-6 hours), which makes the PT/INR coagulation tests most sensitive for testing warfarin's anticoagulation effect. Higher levels of warfarin might prolong aPTT, but is not as reliable for monitoring warfarin's effect.

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  • I figured it might be a matter of PT just being a more sensitive test for warfarin than aPTT and not warfarin having no effect on aPTT at all. Issue is my professors take the latter to be true which added to the confusion. – Dahen May 28 at 16:59

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