H. Gene Hern Jr., Abigail R. Pease, and Nicholas Gavin
Nontraumatic hematuria is surprisingly common, with an estimated prevalence in the general population ranging from 3% to 4% (1). Hematuria may be even more common in older adults; studies using home screening urinalyses in men older than 50 years reported rates of 10% to 20% (2,3). The causes of hematuria, whether it is a chief complaint or an incidental finding, range from sources as benign as vigorous exercise to potentially serious underlying disorders such as infection, renal failure, or malignancy. The challenge for the emergency physician is to differentiate between the serious and nonserious etiologies and determine the appropriate evaluation, treatment, and disposition.
CLINICAL PRESENTATION
Hematuria is generally classified into two categories: gross hematuria and microscopic hematuria. Gross hematuria refers to visibly bloody urine and often presents as a chief complaint. Microscopic hematuria is blood in the urine visible only under the microscope and is often discovered incidentally on urinalysis.
Gross hematuria can be quite distressing to patients. However, in most cases (trauma being the notable exception), there is little correlation between the amount of blood and the seriousness of the cause. Also, the color of the urine does not correlate well with the amount of blood loss; as little as 1 mL of blood in 1 L of urine is enough to discolor the urine. Substances other than blood may discolor the urine red or brown. This condition is called pseudohematuria and may be caused by a variety of conditions such as porphyria, rhabdomyolysis, ingestion of beets or berries, or medications such as phenazopyridine or rifampin (see Table 117.1). Microscopic examination of the centrifuged urine for red blood cells (RBCs) is useful in distinguishing true hematuria from pseudohematuria. The rare discolored specimen that is heme-negative on dipstick and has no RBCs on microscopy indicates a nonheme source. A discolored specimen that is heme-positive on dipstick but without RBCs on microscopy indicates the presence of hemoglobin or myoglobin in the urine.
TABLE 117.1
Causes of Hematuria
Microscopic hematuria is defined by an abnormally high number of RBCs present in the urine on microscopy. The American Urological Association defines asymptomatic microscopic hematuria as three or more RBCs per high-powered field (HPF) on a properly collected urine specimen (4). Although microscopy is the gold standard for diagnosis, the urine dipstick frequently replaces the time-intensive microscopic examination. Urine dipsticks accurately detect hemoglobin in very small quantities, with reported sensitivities from 91% to 100%; the specificity ranges from 65% to 99% (5,6). The high sensitivity results in more false-positive results but fewer false-negative results. A negative urine dipstick thus reliably excludes abnormal hematuria (7). A positive urine dipstick should be confirmed by microscopy to exclude hemoglobinuria or myoglobinuria.
DIFFERENTIAL DIAGNOSIS
The most common causes of nontraumatic hematuria include urinary tract infections, nephrolithiasis, glomerulonephritis, benign prostatic hypertrophy (BPH), and urologic malignancies (Table 117.1). The history and physical examination provide important clues to the underlying diagnosis.
Associated symptoms such as dysuria, urgency, and urinary frequency indicate cystitis as a likely cause. With flank pain, fever, and other systemic symptoms, pyelonephritis should be considered. Unilateral flank pain that radiates to the groin or testicle may indicate nephrolithiasis. Of note, about 15% of patients with renal calculi do not have hematuria, making it an unreliable predictor (8,9). Symptoms of BPH such as dribbling, hesitancy, and poor stream may also suggest the cause of hematuria; new vessels in the proliferating tissue may be fragile and prone to disruption. Some controversy exists as to whether there is a higher incidence of hematuria in patients with BPH than in controls (10,11). Regardless, the presence of BPH should not deter the clinician from further evaluating hematuria, because older men have a higher incidence of cancers of the genitourinary (GU) tract.
A history of a recent sore throat or skin infection should prompt consideration of poststreptococcal glomerulonephritis. Immunoglobulin A (IgA) nephropathy, often also associated with a previous upper respiratory tract infection or pharyngitis, may present with gross hematuria as well. Concomitant hypertension and proteinuria also indicate potential glomerulonephritis. Glomerulonephritis can range in severity from mild asymptomatic hematuria to full-blown nephritic syndrome and renal failure. It is important to note that passage of clots typically excludes the presence of glomerular disease alone and should prompt further urologic evaluation for lower GU etiologies.
In asymptomatic patients, it is important to consider and assess risk factors for urologic malignancy. A number of screening studies in adults with asymptomatic hematuria show a significant risk of urinary tract malignancies, reporting rates of 3% to 5% in women and 7% to 13% in men (3,12,13). Known risk factors for malignancy include age, tobacco use, occupational exposures (e.g., aniline dyes or benzenes), pelvic irradiation, and cyclophosphamide use (5,14).
A family history of sickle cell disease, hemophilia, polycystic kidney disease, or hereditary nephritis can suggest a possible explanation of hematuria. Recent use of medications known to cause nephritis (e.g., penicillins, sulfonamides, cimetidine, and allopurinol) or anticoagulants also may be helpful in suggesting an etiology. It is important to note that hematuria in patients on anticoagulants may originate from a potentially serious lesion and should not be attributed to the anticoagulated state itself. Screening studies show similar rates of hematuria in patients on anticoagulants and in control patients, with rates of urologic cancer the same in both groups (15). A history of travel or residency in Africa or the Middle East should prompt consideration of Schistosoma haematobium, one of the most common causes of hematuria worldwide.
Hematuria in women that occurs during menstruation may be caused by contamination of the urine specimen during collection or by endometriosis of the urinary tract. If contamination by vaginal or perineal bleeding is suspected, obtaining a catheterized specimen after the area has been thoroughly cleaned is recommended. Urethral catheterization itself can produce small amounts of blood in the urine. Studies comparing pre- and postcatheterization urinalyses suggest that more than three to four RBCs/HPF cannot be attributed to catheterization alone (16,17).
Finally, vigorous exercise occasionally produces hematuria (18). Whether from direct contact sports (football, boxing) or other aerobic exercise (biking, long-distance running), exercise-induced hematuria is usually short-lived and benign.
ED EVALUATION
Evaluation of hematuria begins with a urinalysis to confirm the diagnosis of true hematuria. The urinalysis is of further value in determining whether hematuria is glomerular or nonglomerular in origin. On urine microscopy, the presence of RBC casts or a multitude of dysmorphic RBCs is indicative of a glomerular source. Urinary-protein excretion >500 mg/d (on a specimen without gross blood) also indicates probable glomerular involvement. Although these signs are helpful if present, their absence does not rule out glomerular disease.
Coagulation studies should be considered in patients taking anticoagulants. A complete blood count is appropriate for the rare patient with sustained heavy bleeding or evidence of hemodynamic compromise. Electrolytes, blood urea nitrogen (BUN), and creatinine (Cr) should be ordered in patients with suspected glomerulonephritis or symptoms of renal failure. Computed tomography (CT) without contrast should be ordered to evaluate for suspected nephrolithiasis (19). CT also provides information about other potentially lethal causes of hematuria such as abdominal aortic aneurysm (20) and neoplasms of the kidney, ureter, or bladder. When CT is relatively or absolutely contraindicated, particularly in pregnant patients, ultrasound of the kidneys and bladder is the ideal first-line test to assess for nephrolithiasis.
KEY TESTING
• Urinalysis
• Blood urea nitrogen (BUN) and creatinine (if renal parenchymal disease suspected)
• Complete blood count (if significant bleeding or hemodynamic compromise are present)
• Urine culture (if symptoms of infection are present)
• CT scan of abdomen and pelvis without intravenous contrast (in patients with pain and no history of nephrolithiasis)
ED MANAGEMENT
The clinically stable patient with nontraumatic hematuria rarely requires urgent or emergent ED management (see Fig. 117.1). The rare patient with hemodynamic compromise caused by hematuria should be resuscitated with intravenous (IV) crystalloids and blood transfusion as necessary. As always, patients with significant pain and discomfort should receive appropriate analgesics.
FIGURE 117.1 Approach to nontraumatic hematuria.
Further management of hematuria is directed at the cause. Urinary tract infections should be treated with appropriate antibiotics (see Chapter 123). Nephrolithiasis should be treated with analgesics (see Chapter 126). The risk of complications associated with glomerulonephritis (e.g., volume overload, pulmonary edema, electrolyte imbalance, and oliguria) is significant, and thus consultation with a nephrologist is recommended.
With brisk bleeding, often in the postoperative setting, the formation of intravesicular clots can lead to bladder outlet obstruction. This obstruction is managed by placing a triple-lumen urinary catheter to relieve obstruction and then irrigating the bladder with normal saline until the effluent is pink or clear and free of clots.
CRITICAL INTERVENTIONS
• Volume resuscitation of any hemodynamic instability caused by severe hematuria
• Relieving obstruction and irrigating clots with a catheter as needed
DISPOSITION
Most patients with nontraumatic hematuria are managed as outpatients, regardless of cause. Patients with intractable nausea and vomiting, bladder outlet obstruction, renal failure, hemodynamic instability, or signs and symptoms of sepsis should be admitted.
Stable patients with a clear glomerular source of bleeding do not require further ED workup for a urologic source and may be referred to a nephrologist for further evaluation. Asymptomatic nonglomerular hematuria requires outpatient referral to a primary care physician, urologist, or nephrologist but not admission or emergent consultation. Patients older than 35 years, those with gross hematuria, or those with risk factors for malignancy require urgent referral to a urologist for cystoscopy and imaging of the upper urinary tract, typically CT urography. This age cut-off is lower than in past recommendations and is based on the 2012 AUA guidelines (4). Patients younger than 35 years with asymptomatic microscopic hematuria can simply have a repeat urinalysis in 1 to 2 weeks to determine whether hematuria is persistent.
Common Pitfalls
• Failing to provide adequate follow-up for asymptomatic patients with hematuria, especially those who are older than 35 years or who have a high risk of malignancy.
• Eliminating the possibility of ureteral stone based on a negative urinalysis.
REFERENCES
1. Schoolwerth AC. Hematuria and proteinuria: Their causes and consequences. Hosp Pract (Off Ed). 1987;22(10A):45–62.
2. Messing EM, Young TB, Hunt VB, et al. The significance of asymptomatic microhematuria in men 50 or more years old: Findings of a home screening study using urinary dipsticks. J Urol.1987;137(5):919–922.
3. Messing EM, Young TB, Hunt VB, et al. Home screening for hematuria: Results of a multiclinic study. J Urol. 1992;148(2 Pt 1):289–292.
4. Davis R, Jones JS, Barocas DA, et al. Diagnosis, evaluation and follow-up of asymptomatic microhematuria (AMH) in adults: AUA guideline. J Urol. 2012;188(6 suppl):2473–2481.
5. Sutton JM. Evaluation of hematuria in adults. JAMA. 1990;263(18):2475–2480.
6. Woolhandler S, Pels RJ, Bor DH, et al. Dipstick urinalysis screening of asymptomatic adults for urinary tract disorders: I. hematuria and proteinuria. JAMA. 1989;262(9):1214–1219.
7. Schroder FH. Microscopic haematuria. BMJ. 1994;309(6947):70–72.
8. Luchs JS, Katz DS, Lane MJ, et al. Utility of hematuria testing in patients with suspected renal colic: Correlation with unenhanced helical CT results. Urology. 2002;59(6):839–842.
9. Press SM, Smith AD. Incidence of negative hematuria in patients with acute urinary lithiasis presenting to the emergency room with flank pain. Urology. 1995;45(5):753–757.
10. Ezz el Din K, Koch WF, de Wildt MJ, et al. The predictive value of microscopic haematuria in patients with lower urinary tract symptoms and benign prostatic hyperplasia. Eur Urol. 1996;30(4):409–413.
11. Mohr DN, Offord KP, Melton LJ 3rd. Isolated asymptomatic microhematuria: A cross-sectional analysis of test-positive and test-negative patients. J Gen Intern Med. 1987;2(5):318–324.
12. Jones R, Latinovic R, Charlton J, et al. Alarm symptoms in early diagnosis of cancer in primary care: Cohort study using General Practice Research Database. BMJ. 2007;334(7602):1040.
13. Mariani AJ, Mariani MC, Macchioni C, et al. The significance of adult hematuria: 1,000 hematuria evaluations including a risk-benefit and cost-effectiveness analysis. J Urol. 1989;141(2):350–355.
14. Murta-Nascimento C, Schmitz-Drager BJ, Zeegers MP, et al. Epidemiology of urinary bladder cancer: From tumor development to patient’s death. World J Urol. 2007;25(3):285–295.
15. Culclasure TF, Bray VJ, Hasbargen JA. The significance of hematuria in the anticoagulated patient. Arch Intern Med. 1994;154(6):649–652.
16. Hockberger RS, Schwartz B, Connor J. Hematuria induced by urethral catheterization. Ann Emerg Med. 1987;16(5):550–552.
17. Sklar DP, Diven B, Jones J. Incidence and magnitude of catheter-induced hematuria. Am J Emerg Med. 1986;4(1):14–16.
18. Abarbanel J, Benet AE, Lask D, et al. Sports hematuria. J Urol. 1990;143(5):887–890.
19. White JR. Evidence report for imaging in the management of ureteral calculous disease. http://www.auanet.org/content/media/imaging_evidence_report.pdf. Accessed April 22, 2013.
20. Pomper SR, Fiorillo MA, Anderson CW, et al. Hematuria associated with ruptured abdominal aortic aneurysms. Int Surg. 1995;80(3):261–263.