Thin to win

The geriatric consult service was bustling. The warm weather had led our patients into outside activities, like gardening and ATV riding, with resulting falls, fractures, and other gravity-related incidents. We on the service were asked to evaluate Mrs M., a lovely 70-year-old woman, for recurrent falls complicated by a large right thigh hematoma, in the setting of a labile international normalized ratio (INR) of 7 while on warfarin for atrial fibrillation (AF).

It had been on a much colder day, in 1933, when Ed Carlson drove through a blizzard from Deer Park, Wis., to the state capital looking for a cure for his dying cows. He brought a jug of bloody milk and a sample of the spoiled sweet clover that they'd been masticating. It would take another six years for the diagnosis of “sweet clover disease” to lead to the isolation of a substance affecting blood coagulation. With the help of the Wisconsin Alumni Research Foundation (WARF), a new drug was developed and named warfarin.

For Mrs. M., our hope was to make a switch to a direct-acting oral anticoagulant (DOAC), to avoid the wide swings of over- and underanticoagulation she had experienced. However, she had had an aortic dissection the year prior and had received a diagnosis of focal seizure disorder during her postoperative recovery, prompting a cascade of antiepileptic medications, including levetiracetam, which carries an underrecognized but high risk of interaction with DOACs.

Warfarin was first tested on human subjects at Mayo Clinic under the auspices of Hugh Butt, MD, MACP, who was also responsible for some initial studies into vitamin K. The use of warfarin in humans was approved in 1954, and public confidence in it grew in 1955 when President Dwight D. Eisenhower received it after a heart attack. Following several key randomized controlled trials in the 1990s, warfarin's role was cemented for stroke prevention in atrial fibrillation until the 2010 advent of DOACs, praised for their predictable dosing and less frequent need for monitoring and dose adjustment.

Returning to Mrs. M., after some medical detective work, we found that she had no clear indication for antiepileptics and safely discontinued levetiracetam, paving the way to start a DOAC. There was a collective sigh of relief from the medical team and, most important, our patient, who would now be spared INR checks and sub- and supratherapeutic anticoagulation.

This experience taught us something valuable: While our diagnostic tools and risk stratification may have improved over the past 100 years, exposing patients to harmful medicines has never been easier. It's a history lesson that physicians, like cows chewing their sweet clover cud, might find worth ruminating over.