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Minnesota 2020 Journal: My Brush with Anticoagulant Greatness

May 14, 2010 By John R. Van Hecke, Executive Director & Fellow
I owe my health to a diligent early-20th century veterinarian, a Wisconsin biochemist, and the publicly-funded university research community.

Recently, I underwent a routine yet relatively complex surgical procedure. I was released within twenty-four hours, gratefully returning home for some real rest. Things were going swimmingly until day three when my left arm began swelling.

Returning to my clinic, they quickly determined that I had developed a post-operative blood clot, causing my arm's Stay Puft Marshmallow Man appearance. The solution involved anticoagulants, which facilitate circulation and prevent further clotting. I'm also at greater risk for hemorrhaging to death but one problem at a time.

Coumadin is probably the best-known commercial anticoagulant. It's generically called warfarin. For most of us taking Coumadin, the most memorable part, aside from routine blood tests, is the admonition regarding eating dark, leafy green vegetables. The story's short version means I can continue eating broccoli provided that I consume the same amount daily. Otherwise, I start screwing with my Coumadin levels.

Broccoli is a rich source of Vitamin K, a warfarin effectiveness inhibitor. Vitamin K is the antidote to excess warfarin exposure so I have to pay attention to my diet in order to receive warfarin's optimal benefits.

Nearly one hundred years ago, northern Midwestern states and adjacent Canadian province farmers began experiencing a rash of unexplained cattle hemorrhaging deaths. One report cited 21 of 22 cows dying after dehorning and 12 of 25 bull calves dying after castration. All inexplicably bled to death.

Growing up on my family's farm, my parents had a cow-calf herd along with hogs, corn and soybeans. Every winter, we routinely vaccinated the cattle, dehorned them where necessary and turned bull calves into steers. And, I do mean we.

My sister, brother and I had specific age-related responsibilities. Generally, I cut and drove the animals into the stanchion, the head/neck trap mechanism that holds a cow in place. My sister, three years younger, always got to pour a ladle of delousing solution along the cow's spine. She worked closer to our veterinarian, Dr Ray Grefe, which she interpreted as making her job more important than mine but that was thirty-odd years ago and there's no real point dredging up small sibling rivalries.

Whether dehorning or castration, we disinfected and treated the wounds before releasing the cattle back into the feedlot. There was typically some minor bleeding. My father closely monitored his animal's health and I don't recall any serious problems but I can understand the horror that northern farmers must have felt discovering dead calves the next morning.

As the hemorrhaging death crisis mounted, area veterinarians began to take note. Finally, in 1921, a Canadian veterinary pathologist, Dr. Frank Schofield, identified moldy sweet clover silage as the problem's source. Sweet clover, a dark leafy source of Vitamin K, was, through the mold, being transformed into a potent anticoagulant. His observation initiated a chain of research, almost exclusively conducted at state university research labs that culminated at with Karl Link's 1940 work at the University of Wisconsin, isolating the specific anticoagulant agent in spoiled hay.

Several years earlier, Wisconsin farmer Ed Carson hauled a dead cow, a collection of the animal's blood and 100 pounds of sweet clover hay down to Madison, giving Link the research material required to explore the hemorrhaging phenomenon. That finding led to additional work by Link's students extracting and synthesizing warfarin on a large scale. Warfarin is named for their research grant's funder, the Wisconsin Alumni Research Foundation. Besides Wisconsin, clinical trials were also conducted at Rochester's Mayo Clinic.

Warfarin's initial commercial application, still popular today, is rat and mouse pesticides, something I contemplate every time I pop a Coumadin pill. Therapeutic human anticoagulant application came ten years later, almost by chance.

Dr. Karl Link spent years puzzling through anticoagulant's biochemistry. Without his publicly-funded research, not mention that of thousands of other scientists, we might not have Coumadin as a ready, highly effective anti-blood clotting therapy and I'd be in a world of hurt.

The line from a Midwestern farmer's cattle herd to my bottle of Coumadin pills is remarkably direct. The constant, running through the entire narrative, involves public research resources necessary to improve people's lives. As anti-government conservatives rail against government intrusion, I hope they remember that the pill they're swallowing, allowing them to continue ranting, wouldn't exist if conservative public policy had carried the day a century ago.

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