Blood in Urine Carries Consequences for Patients on Antithrombotics

Hematuria is tied to an increase in ED visits and hospital admissions, and may even be a sign of otherwise silent bladder cancer.

Blood in Urine Carries Consequences for Patients on Antithrombotics

Older adults taking antithrombotic medications are at high risk for developing complications related to hematuria, and may wind up visiting the emergency department (ED) or even being hospitalized, according to a new population-based study. They may also need to undergo urologic procedures to investigate or manage their condition more often than those not exposed to these drugs.

“Everybody is worried about life-threatening complications. A bleed in the brain or a bleed in the GI system of course [are] more of a concern, but this is a more prevalent problem and a more common problem that really no one talks about,” senior author Robert Nam, MD, MSc (Sunnybrook Health Sciences Center, Toronto, Canada), told TCTMD.

Nam, lead author Christopher Wallis, MD, PhD (Sunnybrook Health Sciences Center), and colleagues looked at more than 800,000 adults ages 66 years and older who filled at least one prescription for an oral anticoagulant or antiplatelet medication between 2002 and 2014 in Ontario, Canada. Their findings were published online October 3, 2017, ahead of print in JAMA.

Over a median follow-up period of 7.3 years, the rate of hematuria-related complications—including ED visits, hospitalizations, and urologic procedures—was higher for patients in the study group than in those not exposed to antithrombotics (123.95 vs 80.17 events per 1,000 person-years; P < 0.001). Urologic procedures to investigate or manage gross hematuria were the most common among the three events. Complications were generally more common following exposure to anticoagulants compared with antiplatelet agents, with patients reporting the lowest rates after exposure to the oldest medications (ie, aspirin and warfarin). Rivaroxaban (Xarelto; Janssen/Bayer) was associated with the highest rate of complications, regardless of patient age.

Hematuria-Related Events per 1,000 Person-Years by Antithrombotic Agent


ED Visits


Urologic Procedures

No Antithrombotic




Any Antithrombotic
























Other Antiplatelet*




*Clopidogrel, prasugrel, ticagrelor, ticlopidine, and dipyridamole

Patients taking both an antiplatelet and an anticoagulant, regardless of the specific drugs, were at up to a four- and tenfold higher risk for hospitalizations and ED visits, respectively, compared with those unexposed.

Of note, 2.85% of patients presenting with hematuria-related events were subsequently diagnosed with bladder cancer within 6 months. Those receiving antithrombotics had significantly more bladder cancer diagnoses than expected when taking into account the general Ontario population’s risk adjusted for age and sex (standardized incidence ratio 2.38).

Nam said he was surprised to see the volume of hematuria-related problems linked with antithrombotics. “I thought it would be much lower,” he commented. “Certainly [this is] something we can try and work at to prevent, because hospitalizations and emergency [department] visits are never good for the patient. They can lead to kidney failure, infections, discomfort, . . . and can cost the healthcare system a lot of dollars.”

Advocating for better early recognition and counseling by physicians, Nam said hematuria can often be caught before it results in substantial problems. He recommended dose adjustments or temporary breaks from antithrombotics if they are causing hematuria and potentially doing a more thorough investigation to determine the underlying cause of the problem.

Whether it be a cardiologist, surgeon, or primary care physician prescribing the drugs, Nam said all need to be paying more attention to hematuria. Clinicians need “to tell the patient: ‘Look, [antithrombotics] can cause visible blood in the urine. If that happens, don't ignore it. You have to come to the office, and we need to address it,’” he said.

  • Wallis reports receiving support from the Canadian Institutes of Health Research Banting and Best Doctoral Award.
  • Nam reports receiving support from the Ajmera Family Chair in Urologic Oncology.
  • This study was funded by the Ajmera Family Chair in Urologic Oncology and Sunnybrook Foundation. This study used deidentified data from the Institute of Clinical Evaluative Sciences Data Repository, which is managed by the Institute for Clinical Evaluative Sciences with support from its funders and partners: Canada’s Strategy for Patient Oriented Research (SPOR), the Ontario SPOR Support Unit, the Canadian Institutes of Health Research, and the Government of Ontario.