Bleeds on Anticoagulants for A-Fib Can Unveil Occult Cancers

Bleeding in elderly patients with atrial fibrillation who are on oral anticoagulants (OACs) can be a harbinger of as-yet-undetected cancer, observational data on nearly 9,000 patients show.

These latest results, from a Spanish registry, follow those from other studies suggesting that bleeding thought to relate to antithrombotic therapy may in fact be an early warning sign, particularly when it’s seen in urine.

“OACs could be considered as a ‘bleeding stress test,’ which therefore could potentially unveil an occult cancer and improve the chance of early detection,” Sergio Raposeiras Roubín, MD, PhD (Hospital Universitario Álvaro Cunqueiro, Pontevedra, Spain), and colleagues write in their paper, which was published online recently by the Journal of the American Heart Association.

“However, bleeding is not an uncommon complication for patients with AF receiving OACs,” they point out. “In this sense, a provocative question is emerging: should a bleeding event prompt a search for occult cancer in patients with AF treated with OAC therapy?”

The answer, Roubín told TCTMD, is yes.

“Physicians when we see bleeding in our patients on anticoagulation, most of us doctors think: ‘This is the anticoagulation. It’s not a problem,’” Roubín said. Importantly, however, their analyses demonstrate that not only major but also minor bleeding can signal cancer, he pointed out, stressing that specifically gastrointestinal, genitourinary (ie, hematuria and vaginal), and bronchopulmonary bleeds merit attention.

Richard C. Becker, MD (University of Cincinnati College of Medicine, OH), who wasn’t involved in the new study, agreed: “Bleeding, while a known side effect of oral anticoagulants must never be taken for granted.”

These results “serve as an important reminder to patients and clinicians alike that bleeding while on an oral anticoagulant may be an important signal or ‘red flag’ for a serious underlying condition, like cancer,” he commented in an email to TCTMD. “Early identification and treatment may have a major effect on outcome.”

Minor Bleeds Also Matter

Roubín et al analyzed data from the retrospective CardioCHUVI-AF registry on 8,753 patients aged 75 or older who were diagnosed with A-fib between 2014 and 2017. Mean age was 82.7 years, and 61.7% were women. Most (69.6%) received vitamin K antagonists and the rest received direct oral anticoagulants.

Over the course of 3-year follow-up, 5.5% received a diagnosis of cancer. One-quarter of the overall cohort experienced bleeding during this time; among the 2,171 people who did so, 198 (9.1%) were later diagnosed with cancer. Fully 41.3% of all new cancer diagnoses were in patients who’d had a bleed. New cancer rates were similar between vitamin K antagonists and direct oral anticoagulants.

The new cancers were largely identified in the first 6 months after bleeding (35.99%), especially when it came to major bleeds (61.5%). Nearly one in five (18.2%) were diagnosed in the first month.

After adjustment, new cancer diagnosis was increased with any versus no bleeding (4.7 vs 1.4 per 100 patient-years; HR 3.2; 95% CI 2.6-3.9). Especially risky bleeds were GI (HR 13.4; 95% CI 9.1-19.8), genitourinary (HR 18.1; 95% CI 12.5-26.2), and bronchopulmonary (HR 15.8; 95% CI 6.0-41.3). By comparison, other sources of bleeding were linked to a doubling of cancer risk (HR 2.3; 95% CI 1.5-3.6).

More-severe bleeding was more tightly tied to cancer risk, but still 60.6% of cancers were seen in patients who’d had minor bleeding, which tripled the risk of diagnosis. Minor bleeds that were gastrointestinal carried a sevenfold increase in cancer diagnosis, while those in of genitourinary and bronchopulmonary origins each carried a 14-fold higher risk.

The researchers also looked at cancer rates among 1,923 A-fib patients not on OACs, of whom 55.7% were on antiplatelets instead. Cumulative cancer incidence didn’t differ between the anticoagulant and no-anticoagulant groups during follow-up. Yet for the patients on anticoagulation, a higher proportion of their cancers were diagnosed after bleeding than in the absence of bleeding (41.3% vs 17.7%; P < 0.001). Without anticoagulant use, bleeding was linked to higher risk of subsequent cancer (adjusted HR 1.8; 95% CI 1.1-2.9).

‘Proactive Screening’

“A quick proactive screening of cancer after bleeding could potentially provide early detection of cancers and could result in earlier treatment, better prognosis, and possibly increased long-term survival,” the investigators say. They acknowledge that the absolute rates of cancer are low and that routine screening isn’t free or without effort. Still, based on the growing body of evidence, “bleeding in patients receiving oral anticoagulants should prompt a careful search for undiagnosed cancer, even when the bleeding is minor.”

Becker said that overall the cardiology community is aware of this idea. Still, cardiologists “must work closely with primary care providers to make sure that appropriate steps are undertaken should bleeding occur. Indeed, one may choose to stop an anticoagulant because of bleeding, but not necessarily pursue potential reasons,” he observed.

Patients, Becker said, should be urged to inform their physicians about bleeding events, even those that seem less severe. Also, he continued, “one should not interpret the observations from the publication that bleeding can be used as a potential substitute for routine screening measures for cancer.”

Going forward, the most salient area for research, said Becker, is more knowledge about the “interface” between bleeding and the various conditions that require OAC therapy. “There are common risk factors and genetic factors that can be leveraged to either prevent or identify cancers earlier,” he suggested.