How to evaluate ‘dipstick hematuria’: What to do before you refer
ABSTRACTAlthough major health organizations do not support screening for hematuria by dipstick testing, millions of patients without symptoms are tested yearly. Since urinary dipstick tests for hematuria have a high false-positive rate, patients with positive dipstick results require microscopic urinalysis before the diagnosis of hematuria can be made. Primary care physicians can help protect patients from the anxiety, costs, and risks of an unnecessary urologic workup by adhering to the principles of early hematuria management.
KEY POINTS
- Dipstick tests by themselves do not confirm that hematuria is present; thus, “dipstick hematuria” is a potential misnomer. Patients without symptoms who have a positive dipstick test and negative microscopic urinalysis are better described as having dipstick pseudohematuria, a clinically insignificant finding.
- Significant hematuria is defined as three or more red blood cells per high-power field in a properly collected and centrifuged urine specimen; this is the definition that should dictate which patients require further urologic evaluation.
- Since the evaluation for hematuria usually includes cystoscopy and imaging studies, it is crucial to confirm that hematuria is truly present before initiating an invasive and costly evaluation.
CLINICAL RELEVANCE OF HEMATURIA
Approximately 25% of cases of macroscopic hematuria are due to urologic cancers,14,15 and another 34% are due to other significant urologic diseases14—thus, the recommendation that patients with macroscopic hematuria be evaluated by a urologist. In contrast, in microhematuria, the rates of cancer are much lower, ranging between 1% and 10% in large studies.2,5
The urine dipstick test has been found to be 65% to 99% specific for the presence of blood cells, free hemoglobin, or myoglobin.2,5 If the true specificity is closer to the lower figure and all patients with a positive dipstick test were referred to a urologist, this would mean the urologic workup would be unnecessary in up to 35% of them, because the dipstick result would be falsely positive.
But that is not all. Most causes of hemoglobinuria or myoglobinuria are of limited clinical significance, except for rare conditions that are usually clinically obvious, such as severe burn injury. Further, remember that from 9% to 18% of patients without symptoms have red blood cells in the urine.2,5 In theory, if everyone in the United States had a dipstick test, this would be positive in patients with hematuria as well as in those with hemoglobinuria, myoglobinuria, and other false-positives; if everyone with a positive dipstick result were then referred to a urologist, a substantial portion of the population would receive an unnecessary urologic referral.
Urologic referral and evaluation in these patients not only wastes money: if they undergo imaging studies, they are exposed to radiation and contrast media, with their associated risks, and if they undergo cystoscopy, they face its attendant discomfort and risk of infection.
WHICH PATIENTS WITH HEMATURIA TO REFER TO A UROLOGIST
Gross hematuria
Red or tea-colored urine usually indicates gross hematuria. When there is any doubt—such as in the case of a color-blind patient—the presence of red blood cells can be confirmed or ruled out by a microscopic urinalysis.
Nearly all patients with an episode of gross hematuria should be referred to a urologist. The sole exception to this rule can be made when a woman younger than 40 years experiences gross hematuria in the classic setting of a culture-proven, symptomatic urinary tract infection (UTI) and her infection, symptoms, and hematuria all resolve completely with appropriate antibiotics.2,5 However, bleeding from cancer is classically intermittent. Therefore, one should not skip the urine culture and just prescribe antibiotics empirically: the patient might actually have cancer, but the supposed UTI may appear to resolve with antibiotic therapy. For the same reason, resolution of hematuria in any other setting does not obviate the need for referral.
Another scenario usually associated with a benign cause is bleeding after extreme physical activity—also known as “runner’s hematuria” or “march hematuria” (so named because it sometimes occurs in soldiers after a particularly grueling training march). Importantly, even in this situation, one should still be suspicious and probably refer the patient to a urologist: just because the patient has just run a marathon, it does not mean that he or she does not have cancer.
Depending on the character, timing, location, and many other characteristics of the patient’s bleeding, a variety of studies may or may not be necessary. For example, blood-spotting of the underpants might signify urethral bleeding, and imaging and cytologic studies might not be indicated. In view of the variability in presentation and workup, we recommend that the proper workup for these patients be determined by a urologist.
Symptomatic microhematuria
Patients with true microhematuria (three or more RBCs/HPF) accompanied by bothersome or worrisome symptoms should be referred to a urologist. In a study in Scotland, Sultana et al16 found that cancer was present in 6 (5%) of 126 patients with microhematuria without symptoms compared with 13 (10.5%) of 124 patients with microhematuria and irritative voiding symptoms; the difference, however, was not statistically significant.
Microscopic urinalysis should be part of the evaluation for flank pain or certain urinary symptoms such as frequency, urgency, retention, or dysuria; results of this test at the time of symptoms can later help the urologist distinguish the cause of the symptoms or hematuria. In addition, in combination with dipstick analysis, microscopic analysis can help distinguish patients with UTI or medical renal disease. If the evaluation suggests that the hematuria and symptoms are due to a UTI, then the findings on a repeat microscopic analysis, performed after the infection has cleared, should be normal. If hematuria, defined as three or more RBCs/HPF, persists in two of three subsequent urinalyses, then the guidelines mandate diagnostic evaluation even if the urinalysis subsequently becomes negative.
Asymptomatic hematuria
In symptom-free patients with dipstick hematuria found on a screening examination, it is crucial to confirm and document true microhematuria. Per the AUA guidelines, microhematuria worthy of urologic workup is the presence of three or more RBCs/HPF on at least two out of three microscopic urinalyses.2,5 Patients with dipstick pseudohematuria do not meet this criterion and will not benefit from a costly and invasive evaluation. Conversely, patients with higher levels of microhematuria, who have any risk factors for cancer, or who are anxious about the test results might benefit from urologic consultation before a second urinalysis to confirm the first, positive finding.
Many patients younger than age 40 with asymptomatic microhematuria but no other risk factors for urinary tract cancer can be followed conservatively. Khadra et al14 reported that only 1 of 143 patients younger than 40 years with microhematuria had cancer. Similarly, Jones et al17 found, in a prospective study, that no man younger than 40 years with microscopic hematuria had cancer.
Of note: gross or microscopic blood in the urine, even in the setting of anticoagulation, is a marker of urinary tract pathology such as cancer, stones, or infection. Just as patients on anticoagulation therapy who develop gastrointestinal bleeding need a gastrointestinal evaluation, those with hematuria require a urologic evaluation.2,5
