This past fall, I had a pulmonary embolism. This was my second, unprovoked episode -- the first occurred in 2011. Usually after the first event, you leave the hospital with a prescription for an anticoagulant (blood thinning) medication and you'll take it for anywhere between 3 and 12 months. After the second episode, your doctor will likely suggest you stay on anticoagulants indefinitely (or until gene therapy becomes avalable). There are a few anticoagulant options out there now -- Coumadin, Eliquis, Xarelto, and Pradaxa to name a few. So, how did I choose Warfarin?
Coumadin, generically known as Warfarin, is the oldest of these anticoagulants. Having been around since the 50's we've had a lot of time to look at the long term effects and safety of the drug. We also have a reversal agent. Meaning, if you were to have an accident, a cut or bleeding episode, a doctor could administer vitamin K or plasma to reverse the effects of the blood thinner, stopping the bleeding. For the newer generation of anticoagulants, such as Eliquis, there are no reversal agents -- but I've been told they'll be available within the next year. In the meantime, don't wreck your bike.
The wealth of data we have from more than 60 years of Warfarin administration combined with the availability of reversal agents led me to choose Warfarin over the newer anticoagulants on the market. I used it for 6 months following my first PE and had no issues. So, when it came to choosing an anticoagulant last fall, I again chose Warfarin.
Blood clotting is a very complicated, but fascinating, physiological process (check it out here). The details are far beyond my elementary understanding of it and the scope of this blog post. But, I do understand that vitamin K is a necessary cofactor for blood clotting. Warfarin works by inhibiting the enzyme vitamin K epoxide reductase. This enzyme is responsible for reducing vitamin K back to it's active form. Without it, any vitamin K is oxidized and becomes inactive. So, Warfarin essentially works by creating a vitamin K deficiency. This affects many of the vitamin K dependent clotting factors and extends clotting time. On top of Warfarin administration, patients are often instructed to limit dietary vitamin K intake like I was.
This is all well and good -- it works well as an anticoagulant. But, what else is vitamin K needed for?
A few weeks ago, I had a dull ache in my low back after running a workout. In a race not long after that, the dull ache turned into an excruciating knife-stabbing pain near my sacroiliac joint. Three weeks later when I was still hobbling around, an MRI showed I had fractured my sacrum during that race.
It wasn't until I started worrying about a stress fracture that I looked into Warfarin's interaction with vitamin K and bone health. There are no warnings related to bone health and Warfarin use. Your doctor or pharmacist probably won't tell you there is any interaction between the two. And there is no mention of decreased bone turnover and bone mineral density or increased risk of fracture in the list of "possible side effects."
But take a look for yourself:
Long-term warfarin therapy and biomarkers for osteoporosis and atherosclerosis.
Bone density in children with single ventricle physiology.
Warfarin Use and Baseline Bone Mineral Density in the Population-Based Canadian Multicentre Osteoporosis Study
Vitamin K-dependent carboxylation of osteocalcin affects the efficacy of teriparatide (PTH(1-34)) for skeletal repair.
Effect of long-term oral anticoagulant therapy on bone mineral density and bone turnover markers: a prospective 12 month study
Oral anticoagulant drugs and the risk of osteoporosis: new anticoagulants better than old?
Bone health and osteoporosis: the role of vitamin K and potential antagonism by anticoagulants.
Of course, I recognize that in my anecdotal observations, n=1. I'm not saying Warfarin is the reason I developed a sacral stress fracture. I was training very hard. But, there is a great deal of research demonstrating an interaction between Warfarin and bone formation. It is time practitioners and pharmacists recognize the possible side effects Warfarin has on bone turnover acutely and what that means for long term bone mineral density. Further, researchers should recognize the need for more data on Warfarin's effects on bone health in young athletes, especially those vulnerable to fractures.