Incidence of Visible Hematuria Among Antithrombotic Agents: A Systematic Review of Over 175,000 Patients

Abstract

Objective: To determine the probability of visible hematuria with antithrombotic agents and to evaluate association of urologic etiology in antithrombotic-related hematuria.

Methods: Preferred Reporting Items in Systematic Reviews and Meta-Analyses guidelines were followed to conduct a systematic review using search engines PUBMED and SCOPUS with the terms "(hematuria) OR (haematuria) OR urinary bleeding)) AND ((anticoagulants) OR anticoagulation) OR noac) OR novel anticoagulants) OR antiplatelet) OR dabigatran) OR rivaroxaban) OR apixaban) OR warfarin) OR aspirin) OR heparin) OR dipyridamole)." Raw data were used to perform a pooled analysis. Chi-square and logistic regression analysis were used for statistical analyses.

Results: Twenty-two studies describing 175,114 patients met inclusion criteria. Odds ratio of hematuria with warfarin to rivoraxaban was 33 and warfarin to dabigatran was 16. The odds ratio of hematuria for oral anticoagulant (26.7%) to prophylactic parenteral anticoagulant (1.1%) agents was 9.6. Antiplatelet agents are 76 times less likely to cause hematuria compared to anticoagulants. Odds of hematuria with aspirin were 6.7 times the odds with clopidogrel and 3.5 times the odds with ticagrelor. Dabigatran was 198 times more likely to cause major hematuria compared to warfarin, whereas clopidogrel is 1.2 times more likely to cause major hematuria compared to aspirin. Urologic pathology was identified in 44% (234/532) of cases, malignancy in 24%.

Conclusion: Warfarin use poses the greatest risk for hematuria but is unlikely to cause major hematuria, whereas novel antithrombotic agents are more commonly associated with major hematuria. This review further characterizes the risk profile of antithrombotic agents and associated hematuria to equip clinicians with knowledge to choose an appropriate antithrombotic agent in patients with high-risk hematuria.