A 58-Year-Old Man With Episodes of Painless Hematuria

Ronald Rubin, MD—Series Editor

Volume 57 - Issue 1 - January 2017

A 58-year-old man presents for evaluation of hematuria. He had been in his usual state of health until approximately 2 weeks ago, when he experienced an episode of hematuria in the middle of the day. 

There had been no associated flank, penile, or other discomfort either with the episode or in the time periods before or after the episode. Since then, he has had 2 more hematuria episodes. However, a week has passed without hematuria, and he is in the office at his wife’s prompting.

He is otherwise healthy, without hypertension or diabetes. He works as an auto dealership executive. He has been an active smoker for 35 years, with a 25-year history of having smoked a pack or more per day, and in the last 10 years, a half pack per day. He has experienced atrial fibrillation and takes dabigatran daily.

The physical examination is quite nonrevealing. Findings of head, eyes, ears, nose, and throat examination are normal. His chest is clear to auscultation and percussion. His heart has a regular rhythm with frequent premature atrial contractions. His abdomen is normal, without palpable mass or tenderness anteriorly or in the flanks. There is no enlargement of the inguinal lymph nodes. His prostate is slightly enlarged but is smooth and without nodules.

All routine laboratory test results are normal. Three urinalysis samples were taken at intervals; while the results of 2 were totally negative, a third revealed microscopic hematuria.

 

Answer: C, patients with gross hematuria should be referred for urologic evaluation, even if the hematuria is self-limited.

Gross hematuria is a striking and important symptom that has a clear association with dangerous causative diagnoses and thus triggers a classical diagnostic protocol in most patients’ cases. The first separating point in evaluation is the absence of pain with hematuria. The presence of hematuria with pain, most often flank or groin pain (“renal colic”), usually means kidney stones and initially will proceed down that diagnostic and therapeutic pathway.

Gross hematuria in the absence of pain is associated with far more ominous underlying causes, with a pretest probability of between 10% and 25% for serious genitourinary tract disease and an odds ratio for urologic cancer of 7.2,1-3 including cancer of the bladder or kidney. In the case presented here, the patient had several important risk factors for urinary tract cancer. In addition to the demographics of being a man over the age of 50, he is a rather heavy smoker, which is a major risk factor. Other risk associations with hematuria that are less common yet important include are exposure to chemical dyes and abuse of analgesic medications. However, the finding of gross hematuria itself trumps them all.

The typical and accepted evaluation in cases of painless hematuria involves referral for urologic evaluation, including cystoscopy to directly visualize the bladder and contrast-enhanced computed tomography (CT) urography of the upper tract if there are no contraindications to that test. If a mass is detected, appropriate biopsy methods are then used to confirm or exclude a tissue diagnosis of malignancy. The current specificity and sensitivity of less-direct methods of diagnosis, such as urine cytology and urinary molecular markers for bladder cancer, are not yet adequate to suggest their use to definitively confirm or exclude a specific diagnosis of malignancy in patients with hematuria.1,4 And cystoscopy with biopsy will be required in any event for staging and subsequent care planning. Thus, Answer D is not an accurate statement.

The patient in our case had a flurry of episodes of gross hematuria, which subsequently abated; that situation often results in delay or even aborting of urologic evaluation.5 Intermittent hematuria that later is proven to be the result of underlying neoplasm occurs frequently enough and the odds of finding malignancy are sufficiently high in gross hematuria situations such that evaluation should promptly proceed. Thus Answer C is the most correct statement.

Regarding the appropriateness of using urinalysis in asymptomatic patients to screen for microscopic hematuria (a very different setting and patient group than gross hematuria), the preponderance of evidence is that the risk for underlying genitourinary tract cancer is too low (positive predictive value, 0.2%-0.5%) and is not significantly different from cancer incidence figures in nonscreened populations to justify its use.1-3 Screening of healthy, asymptomatic patients for genitourinary tract cancer using urinalysis to detect microscopic hematuria is not currently recommended by any major health organization,1 and Answer A is not a correct statement.

Finally, the presented patient was on anticoagulation therapy (dabigatran). Many clinicians essentially accept that appropriately anticoagulated patients can be expected to have episodes of bleeding related to their anticoagulant regimen. This is simply not the case. In the absence of over-anticoagulation (eg, patients on warfarin with an international normalized ratio of 2 to 5; patients on standard regimens of novel oral anticoagulants without creatinine elevations), abnormal bleeding is not to be expected and should be evaluated in the usual manner, with subsequent demonstration of pathology being as many as 80% of cases.6 Thus, Answer B is also an incorrect statement.

Patient Follow-Up

The patient was referred for urologic evaluation. Cystoscopy revealed a papillary tumor of the bladder, which biopsy results showed to be a well-differentiated transitional cell carcinoma. CT scans revealed no pathology in the upper urinary tract. The patient underwent a partial cystectomy for curative intent and was disease-free at 1 year of follow-up.

Ronald Rubin, MD, is a professor of medicine at the Lewis Katz School of Medicine at Temple University and is chief of clinical hematology in the Department of Medicine at Temple University Hospital in Philadelphia, Pennsylvania.

References:

  1. Nielsen M, Qaseem A; High Value Care Task Force of the American College of Physicians. Hematuria as a marker of occult urinary tract cancer: advice for high-value care from the American College of Physicians. Ann Intern Med. 2016;164(7):488-497.
  2. Loo RK, Lieberman SF, Slezak JM, et al. Stratifying risk of urinary tract malignant tumors in patients with asymptomatic microscopic hematuria. Mayo Clin Proc. 2013;88(2):129-138.
  3. Jung H, Gleason JM, Loo RK, Patel HS, Slezak JM, Jacobsen SJ. Association of hematuria on microscopic urinalysis and risk of urinary tract cancer. J Urol. 2011;185(5):1698-1703.
  4. Davis R, Jones JS, Barocas DA, et al; American Urologic Association. Diagnosis, evaluation and follow-up of asymptomatic microhematuria (AMH) in adults. AUA guideline. J Urol. 2012;188(6 suppl):2473-2481.
  5. Friedlander DF, Resnick MJ, You C, et al. Variation in the intensity of hematuria evaluation: a target for primary care quality improvement. Am J Med. 2014;​127(7):633-640.e11.
  6. Hurlen M, Eikvar L, Seljeflot I, Arnesen H. Occult bleeding in three different antithrombotic regimes after myocardial infarction: a WARIS-II subgroup analysis. Thromb Res. 2006;118(4):433-438.