Pharmacology/Pathophysiology Question

Question

A new mother is admitted to the intensive care unit and started on low-molecular-weight heparin and warfarin. She is told that she will be discharged in a day or two and will remain on the heparin for 5 days and the warfarin for at least 3 months.  

1. What are the actions of heparin and warfarin? 
2. Why is heparin administered for 5 days during the initiation of warfarin treatment? 
3. Anticoagulation with heparin and warfarin is not a definitive treatment for clot removal in pulmonary embolism, but a form of secondary prevention. Explain.   

Answer 1

Ok lets start by breaking this question down. Ironically this is very reminiscent of a real patient that I had while in clinical practice as a hospital pharmacist.

What has likely happened? My guess is that the young lady in question has suffered a DVT (deep vein thrombosis). Inactivity causes blood clots to form in the veins usually in the legs. She has been put on a low molecular weight heparin (eg: Lovenox)

1. What are the actions of heparin and warfarin?

Strategy: To answer this question we have to review the mechanism of action for both of these drugs and it wouldn't hurt to review the blood clotting cascade. A good schematic can be found at this link:

https://www.google.com/url?sa=i&url=https%3A%2F%2Fjeb.biologists.org%2Fcontent%2F220%2F3%2F455%2FF1&psig=AOvVaw2W80BrL9pWOpBDIhqsbghp&ust=1613514896456000&source=images&cd=vfe&ved=0CAIQjRxqFwoTCIDj88P57O4CFQAAAAAdAAAAABAT

Lovenox binds to and potentiates antithrombin III, a serine protease inhibitor, to form a complex that irreversibly inactivates factor Xa.

This is going to prevent clots from getting bigger. It has a shorter half life (usually dosed twice a day)

Now that she has had a clot we need to prevent clots, but it isn't very practical to give her Lovenox for months on end. So we use heparin. So this leads to our second question:

2 Why is heparin administered for 5 days during the initiation of warfarin treatment? 

To answer this we ask: what is the mechanism of action of warfarin? Warfarin prevents new clots from forming by inhibiting factors II, VII, IX, and X. But it takes a while for this to happen. You measure what is called the INR to keep track of anticoagulation. A person not on anticoagulation normally has an INR of 1 (absent liver issues, but that's a whole other topic for discussion). To make a long story short when you measure the INR you aren't seeing the effect of todays dose. You are seeing the effect about 3 doses ago. So it takes a while to kick in. This is part of the reason that a low molecular weight heparin is used to "bridge" the warfarin dose.

The other reason that a low molecular weight heparin is used to bridge the warfarin is because warfarin also inhibits protein C and S. These are the body's natural anticoagulants. So during the first few days of warfarin therapy the odds of a clot goes up instead of down. By the time INR is between 2-3 the anticoagulant action overpowers the "pro-coagulant" action

And this leads to our final question:

Anticoagulation with heparin and warfarin is not a definitive treatment for clot removal in pulmonary embolism, but a form of secondary prevention. Explain.  

Read what I said earlier very carefully. I said that warfarin keeps a clot from getting bigger, and warfarin prevents new clots from forming. Neither of these options can do anything to an already existing blood clot. To take care of that you usually need tPA.

Let me know if this helps.