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Late last year, an 83-year-old arrived at University Hospital's emergency room shaken from a fall, but alert and oriented.
He had fallen from standing level, but was taking a new blood thinner, Pradaxa, and initial scans revealed a surprising amount of bleeding in the brain, said Sarah Garber, one of the doctors who treated him. "We were concerned from the start."
He declined quickly, lapsing into a deep coma within six hours. Repeat scans showed blood had nearly filled the left side of the brain and a good portion of the right.
He died soon after, prompting Garber and her colleagues to publish a case report alerting physicians and patients to the risk of uncontrollable bleeding with a new type of blood thinning medication, called direct thrombin inhibitors.
The study, published Tuesday in the Journal of Neurosurgery, adds to a growing chorus of concern about the drug at a time when similar medications are poised for approval by the U.S. Food and Drug Administration [FDA].
Approved in October 2010, dabigatran etexilate, or Pradaxa, has been shown in clinical trials to do a better job than other blood thinners at reducing the risk of stroke in some patients, say the authors. It's easier for doctors to administer than the leading blood thinner warfarin, which can interact with food and other medicines, requiring monthly blood testing to tailor the dose.
But once bleeding starts, it's largely irreversible, because there's "no known agent" to counteract Pradaxa's effects, said Garber, a neurosurgery resident.
Pradaxa is prescribed to prevent strokes and blood clots in people with heart valve disease. But the drug works differently than warfarin, which is easily blocked with an injection of vitamin K.
The only recognized treatment for a Pradaxa-induced bleed is dialysis, which take hours to help patients eliminate the drug through their kidneys, the U. study says. High doses of clotting drugs have been shown to help in mice.
The 83-year-old Salt Lake City man had an enlarged heart valve. In addition to Pradaxa, he was taking medications to control his cholesterol and gastric reflux.
Garber couldn't say with 100 percent certainty that the blood thinner was the cause of his death, but she does not believe the other drugs contributed.
The FDA says pharmacies dispensed Pradaxa to 371,000 patients between October 2010 and August 2011. The agency is evaluating whether reports of serious bleeding events in patients taking Pradaxa are "occurring more commonly than would be expected. In a December advisory, the agency noted bleeding is well-known complication of blood thinners, citing a large clinical trial with 18,000 volunteers in which major bleeding events in patients using Pradaxa or warfarin occurred at similar rates.
An FDA spokeswoman on Tuesday could not immediately say whether any of those deaths involved falls.
The number of bleeding deaths among Pradaxa patients multiplied by five in just a couple of weeks, according to a report from Reuters. The drugmaker, Boehringer Ingelheim, has confirmed 260 reports of fatal bleeding among Pradaxa patients worldwide, up from the 50 deaths the company acknowledged at the start of November. Boehringer Ingelheim agreed to notify European doctors that patients older than 75 and those with renal impairment should undergo kidney checks every year, Reuters said.
In a November statement, the drug company said serious bleeding events can and do occur with all anticoagulants, including Pradaxa. "Importantly, the bleeding events and fatal bleedings reported to date are considerably fewer than expected based on the trial data that support the use of Pradaxa in clinical practice," the company said.
But in January, the nonprofit Institute for Safe Medication Practices said "review of [dabigatran's] adverse effects in high risk patients deserves to be a national priority."
The institute's analysis examined data from the FDA's Adverse Event Reporting System for the first quarter of 2011. "Overall," it said, "932 serious adverse events were linked to this drug, including 120 deaths, 25 cases of permanent disability, and 543 cases requiring hospitalization."
The 505 cases that involved hemorrhages were more than any other monitored drug, it said. Warfarin ranked second, with 176 hemorrhage cases.
The patients who had cases related to hemorrhages had a median age of 80, with a quarter of them age 84 or older, the institute said, "raising a question regarding safe dosing and monitoring in older patients."
The drug is heavily advertised on TV. Boehringer Ingelheim launched its Pradaxa advertising campaign with a television ad during the Kentucky Derby in May, according to Medical Marketing & Media, a New York-based company that represents pharmaceutical companies.
Ads have aired on Good Morning America, Dancing with the Stars and during network news broadcasts. Magazine ads were scheduled for Good Housekeeping and Country Living magazine. "The campaign targets an older audience, mainly 65 and up," the marketing company said on its web site.
For now, warfarin remains a more popular choice, but Pradaxa is a "new medicine that does what it's supposed to do," said Raymond Ward, a doctor in Bountiful and member of Utah Medicaid's Pharmacy and Therapeutics Committee.
But he hasn't switched his patients over.
"I'm not convinced it's superior and think the risks are still shaking out," he said. Pradaxa by the numbers
371,000 • The number of patients who received Pradaxa prescriptions from pharmacies between October 2010 and August 2011, according to the FDA.
18,000 • The number of volunteers in a clinical study that showed major bleeding events in patients using Pradaxa or warfarin occurred at similar rates.
11,440 • The number of Utahns who filled 41,292 prescriptions for warfarin in 2010, according to data from the state's All Payer Database, a repository of commercial insurance claims.