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    Asymptomatic Hematuria

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    Today’s clinical question/topic, that I will discuss, is how much blood in the urine is too much? What if it’s asymptomatic hematuria?

    The short answer, to the question, is that it varies case by case.

    For an 18-year-old female, who is on her menstrual period, we would expect to see hematuria on a UA dip.

    A 41-year-old female, with a UTI, might be expected to have some hematuria there as well.

    How about for a 31-year-old male that is asymptomatic?

    We will cover the topic of hematuria, that is seen on an in-office dipstick, and the steps which should be taken.

    Blood on Dipstick – Now What?

    The first fork in the tree of decision making comes when blood is seen in the office dipstick. Regardless of the amount (trace, small, moderate, or large), my next step is to send the sample for microscopic evaluation.

    Sometimes, you will have a false positive from your in office dipstick (confirmed by microscopy). If this is the case, then no further workup would be needed.

    False positives can occur in hemoglobinuria, myoglobinuria, the presence of semen, or with pH >9 of the urine. In contrast, false negatives on a dipstick have been seen in patients taking Vitamin C supplements.

    However, if there are >3 RBCs/HPF seen on microscopy, further decisions need to be made.

    In the remainder of this review, I will be discussing patient’s that have asymptomatic microscopic hematuria. Obviously, if worrisome symptoms are presenting with the hematuria, the workup changes.

    Asymptomatic Hematuria is Confirmed

    Asymptomatic hematuria will be something you frequently encounter in primary care. During routine health screenings, it is found 2% to 31% of the time.

    In these patients, workup for an underlying etiology and referral is appropriate, since in 5% of these cases, malignancy is found to be the cause.

    Unfortunately, studies have revealed that these guidelines for evaluation are not regularly followed, which results in unneeded referrals, or worse, failure to find treatable causes from the beginning.

    Etiologies For Asymptomatic Hematuria

    There are many causes for microscopic hematuria:

    • UTI
    • Menstruation
    • Excessive exercise
    • BPH
    • Kidney disease
    • Urinary calculi
    • Urethral stricture
    • Malignancy

    Other than unknown etiologies, the most common cause is typically found to be a UTI at 4% to 22%, followed by BPH at 10% to 13%.

    Urologic malignancies are overall the least common etiology, ranging from <1% to 4% of causes, but these are the cases that must be caught.

    The likelihood of malignancy is increased in males, those over 35 years of age, and those who are currently or have a history of smoking. Other risk factors include analgesic abuse, chemical exposure to benzenes or aromatic amines, or history of chronic catheterization, chronic UTI, exposure to carcinogenic agents or alkylating chemotherapeutic agents, irritative voiding symptoms, and pelvic radiation (Am Fam Physician. 2013 Dec 1;88(11):747-754.).

    Managing Asymptomatic Hematuria

    I typically repeat a UA with microscopy in 4-6 weeks, even if a UTI was diagnosed. I also repeat in the asymptomatic patient if there is >3 RBCs/HPF seen on microscopy .

    If the follow-up UA microscopy is negative, I repeat an additional UA microscopy evaluation, separated by six weeks to assure hematuria isn’t present.

    Some providers might elect to stop if the second UA shows resolution.

    If all three of these evaluations return normal, then no further workup is indicated (this is considered dipstick hematuria). However, if any one of the three tests return positive (>3 RBCs/HPF), then further testing is needed.

    There are some other things to look at on the microscopy that might point you in one direction versus another

    • Dysmorphic RBCs or cellular casts are present
    • Elevated serum creatinine
    • History of hypertension

    If these are present, then renal etiologies should be considered.

    These include IgA nephropathy, Alport syndrome, benign familial hematuria, or other nephropathies.

    If these causes were suspected, additional workup and referral to nephrology would be indicated.

    Imaging Studies

    Even if there is suspicion of a renal disease as above, a concomitant urology workup should begin. After the establishment of microscopic hematuria is made, a CT urogram should be completed.

    A CT urogram involves a noncontrast phase to evaluate for hydronephrosis and calculi, a contrast nephrogenic phase which looks for renal masses, neoplasm, or pyelonephritis, and a contrast excretory phase to assess for urothelial disease.

    In those with renal disease, that cannot have contrast, or in pregnant patients in which radiation needs to be avoided, I would order a renal ultrasound and depending on the results, move to an MRU (magnetic resonance urogram).

    Retrograde pyelography with renal ultrasound or noncontrast CT could be considered as well.

    What to do After Imaging?

    After the completion of the imaging, if an underlying etiology is revealed, referral to urology should be made.

    If an etiology is still not found, referral to urology should still be made for evaluation of the lower urinary tract.

    In all patients with asymptomatic hematuria, a cystoscopy is recommended, which is why urology referral needs to be completed.

    Cystoscopy can find urethral stricture disease, BPH, and bladder masses. In those younger than 35 years of age the likelihood of urologic malignancy is low, and sometimes a cystoscopy will be deferred, but this should be determined by the urologist.

    Before entering physician assistant school, I worked at a histology technician, and a test we would often perform for the urologist in the area was urine cytology. It has been found that this test is less sensitive than a cystoscopy for bladder cancer.

    In fact, the AUA no longer recommends that this test be included in the routine workup of microscopic hematuria.

    Other novel testing includes rapid urine assays for bladder cancer detection.These include the nuclear matrix protein 22 test, bladder tumor antigen stat test, urinary bladder cancer antigen, and fluorescence in situ hybridization.

    These new tests, however, have not been shown to be better than cystoscopic evaluation, or even cytology.

    Idiopathic Hematuria

    Often, in asymptomatic microscopic hematuria cases, the etiology is not found 43% to 68% of the time. In these cases, if the patient is given as needed follow up from urology.

    I will repeat a microscopic urinalysis yearly for two years. If both return normal, without hematuria, the likelihood of future urologic malignancy is <1%.

    However, if either of these microscopic urinalyses returns positive for microscopic hematuria, the above workup should be reconsidered within three to five years of the initial evaluation.

    Regarding the workup for asymptomatic hematuria, there is one caveat. If a patient has asymptomatic hematuria, and they are on anticoagulants, they require referral to urology and nephrology immediately.

    In the location where I practice, I often begin the workup with imaging, due to length of time it takes for them be seen by the specialist, but the referral needs to be placed urgently.

    Conclusion for Asymptomatic Hematuria

    Just like with most lab results, there are clinical decision-making skills that must be made. This is no different with microscopic hematuria.

    I hope this article supplied you with some tools to help make this evaluation more comfortable for you in practice.

    So, back to the initial question, how much blood in the urine is too much? The best answer would be any amount, because no matter how much or how few, follow up with repeat urinalysis is needed.

    Resources
    Am Fam Physician. Assessment of Asymptomatic Hematuria in Adults. 2013 Dec 1;88(11):747-754.
    Am Fam Physician. Bladder Cancer: Diagnosis and Treatment. 2017 Oct 15;96(8):507-514.
    UpToDate. Etiology and Evaluation of Hematuria in Adults. Accessed: November 11, 2017.

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    Clay Walker
    Clay Walker is a board-certified physician assistant practicing in family medicine and urgent care in rural southern Illinois. He is a graduate of Southern Illinois University School of Medicine Physician Assistant Program - class of 2016. Prior to going to PA school, Clay worked as a histology technician in southern Illinois.  From an early age, he has been interested in medicine. Clay was diagnosed as a type 1 diabetic in the first grade. He began learning about his condition and teaching others about T1DM; since then, he began to have a passion to learn medicine and make a difference in the lives of others. In his free time, Clay enjoys watching sports and going to sporting events, specifically the Chicago Cubs and Philadelphia Eagles.