I had some good questions based on the post on the intrinsic and extrinsic pathways from last week. I really love it when you write in with questions! There are a couple related posts that you might want to take a look at if you need a little refresher: How Coumadin and heparin act on the coagulation cascade, How does Coumadin work? and Coagulation tests in 400 words or less.
Coumadin and the INR
Q. So this is the way I see it: If I use Coumadin starting with a low dose working up, I will “paralyze” the extrinsic system by lowering Factor VII before I “paralyze” the other vitamin K dependent (II, IX, X) factors. This prolongs the INR but leaves the PTT intact.
A. Yes! Exactly. Eventually, the PTT will become prolonged too – but initially, the INR is the first thing to become abnormal (check out How does Coumadin work? for a review of, well, how Coumadin works).
Heparin vs. Coumadin
Q. Is heparin is a “stronger” anticoagulant because it inhibits thrombin at the end of the common pathway (which knocks out the effects of both the intrinsic and extrinsic systems)?
A. It’s not exactly stronger – it just acts at different places in the cascade. Both heparin and Coumadin affect several different factors, and both are very effective – they just have different clinical applications.
Factors tested by the INR
Q. If you give a patient heparin (assuming no Coumadin is given), will the INR will remain normal in the lab because the INR doesn’t test beyond the factor VII contribution in the chain of events?
A. No – the INR tests factor VII as well as all the factors in the final common pathway. Heparin acts by potentiating antithrombin III, which has effects on factors in both the intrinsic and extrinsic as well as final common pathways (including thrombin, as you mention). So if you give a patient heparin, both the INR and the PTT will be abnormal.
Deep venous thrombosis treatment
Q. So for deep venous thrombi, patients are given both heparin and Coumadin (starting with a low dose of Coumadin and working up) while monitoring the INR to watch for the effects of Coumadin- right?
A. Yes! Also, it turns out that in addition to the regular vitamin-K dependent coagulation factors (II, VII, IX and X), the anticoagulant proteins C and S are also vitamin-K dependent, and therefore susceptible to the actions of Coumadin. AND it turns out that the half lives of proteins C and S are actually SHORTER than the half lives of the rest of the vitamin K dependent coagulation factors! Protein C has a half life of somewhere around 7 hours, and the vitamin K dependent factors have roughly a 40 hour half life overall (though factor VII is much shorter). So for a brief period of time, there is actually a PRO-coagulant effect of Coumadin on the patient (because the first things to disappear are proteins C and S).
This usually doesn’t affect patients clinically, because most people have enough protein C and S (and enough of the other anticoagulants, presumably) that a little diminishment in proteins C and S isn’t hazardous. However, in patients with protein C or S deficiency, this phenomenon can be deadly.
Giving heparin protects against this dangerous early pro-coagulant action of Coumadin, because heparin acts immediately (as you mentioned), and therefore provides a nice anticoagulant effect to cover the period of time where Coumadin inhibits proteins C and S.
Very important Couagulaton Profile Assaying info,helpful & lifesaving….::
As a nurse of 20+ years have brushed up against DIC a number of times. I greatly appreciate the questions from the students and the answers from Dr Kraft’s. Most excellent questions and most excellent and concise answers. Thank you.
Thanks, Mark!! It’s great to get a compliment from such an experienced person!
Great article! I’m about to take USMLE step 1, thanks for the help!
Great! Good luck!
As a medical student who is about to take STEP1 it also confused me when books said that heparin affects factor 7a yet there was no mention of it affection PT/INR. It does however not as much to significantly affect PT(which is for the intrinsic/common pathway) therefore aPTT which it does affect significantly is used to assess it.