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Genitourinary Hemorrhagic Complications and Malignancies in Patients Receiving Anticoagulation Therapy.

long-term use (>2 years) of pioglitazone, an oral hypoglycemic agent for diabetes mellitus, increased the risk of bladder cancer among diabetic patients (hazard ratio, 1.4; 95% confidence interval, 1.0–2.0).3 Subsequent pooled multipopulation analysis revealed that the cumulative use of pioglitazone was not associated with the incidence of bladder cancer.4,5 However, the impact of the first result was larger than the beneficial effect of pioglitazone and the use of this drug has decreased worldwide, despite it being reported to reduce the risk of macrovascular events such as nonfatal myocardial infarction, stroke, and all-cause death in patients with type 2 diabetes.6 Therefore, the mitogenic potency and oncogenicity of drugs should be taken into account, especially in patients who are undergoing longterm drug therapy. Fortunately, there has been no evidence that warfarin itself increases the incidence of renal or bladder cancer. Conversely, an anticancer effect of warfarin can be found in some reports, in which the long-term use of warfarin was associated with a lower incidence of prostate cancer.7–9 These findings support the first hypothesis. Age is a strong risk factor for the incidence of cancer. Indeed, the odds ratio for genitourinary cancers in patients H emorrhagic complications are a perpetual problem in any patient receiving anticoagulation therapy, not only in those with atrial fibrillation (AF). Net clinical benefit of anticoagulation therapy can be obtained when the incidence of hemorrhagic events is less than that of thromboembolism.1 Therefore, physicians have always considered the balance of risk (i.e., hemorrhagic complications) and benefit (i.e., prevention of thromboembolism) to achieve positive results of anticoagulation therapy. Although hematuria is a common and important hemorrhagic complication, along with intracranial hemorrhage and gastrointestinal bleeding, there is little information about genitourinary tract bleeding during anticoagulation therapy in preceding studies. In this issue of the Journal, Yu et al2 focus on hematuria and genitourinary complications in patients with AF receiving oral anticoagulation therapy (OAT). The authors clearly demonstrate that the frequency of hematuria and its grade are higher in patients with OAT than in those not on OAT. The prevalence of bladder cancer was higher in patients with OAT, even in the propensity score-matched population, and the risk of bladder cancer was associated with urine red blood cell (RBC) grading. The odds ratio for genitourinary cancers in patients with urine RBC grade 3+ and gross hematuria was significantly higher compared with patients with urine RBC grade 1+ (Figure 1A).2