Microscopic hematuria (MH) is a common incidental finding present in up to 1 in 5 women.¹ MH may indicate presence of underlying pathology such as urothelial cancer, urolithiasis, or infection; however, only 30% of patients presenting with MH are found to have an identifiable cause.¹,² Many existing guideline recommendations for evaluation of MH reflect male urologic malignancy risk despite known gender disparities in urologic cancer.³ In the female patient demographic, unconstrained investigation of patients with MH may lead to individual and public health implications associated with adverse clinical and economic effects.⁴,⁵ Despite this, bladder cancer remains to account for 125,000 cancer diagnoses in women worldwide annually; therefore, a risk-stratified approach to evaluation and management of MH is essential.⁶

Terminology and definitions used for MH can vary; the terms “microscopic hematuria,” “microhematuria,” “nonvisible hematuria,” and “dipstick hematuria” are all commonly and interchangeably used. The definition of MH varies according to guidelines; however, majority require microscopic evaluation for diagnosis with a threshold ranging from 2 to 25 red blood cells per high-power field (RBCs/HPF).⁷,⁸,⁹ An appropriately collected urine sample for interpretation requires a freshly voided, clean-catch, midstream specimen.⁷,⁹ Dipstick hematuria is a common incidental finding because it is a universally used screening tool for a variety of indications. It is important to note, however, that urine dipstick analysis can be prone to false positives due to myoglobinuria, dehydration, and menstrual blood among other factors.¹⁰ It is for this reason that most guidelines suggest that dipstick hematuria be further investigated with formal urine microscopy for diagnosis of MH to be confirmed.⁷ A single finding of MH on urine microscopy is sufficient to warrant further investigation due to the known transient nature of MH present in even malignant conditions.

Causes of MH can be classified according to anatomical site of origin (kidney, ureter, bladder, urethra) or etiology (malignant, obstructive, infectious/inflammatory, nephrogenic, transient) (Table 39.1). Transient and benign causes for MH, such as urinary tract infection, trauma, viral illness, vigorous exercise, and recent urologic instrumentation, should be considered prior to commencing initial evaluation for underlying pathology.¹¹ Additionally, female-specific conditions such as urogenital tract atrophy, pelvic organ prolapse, and menstruation can lead to urinary contamination resulting in false-positive findings of MH.⁹,¹²,¹³ In these patients, a clean-catch specimen may be obtained using in-and-out catheterization to avoid introital contamination.

Hematuria is an established clinical indicator for bladder cancer, a disease that results in 200,000 deaths worldwide annually and attributable to 3% of new cancer diagnoses.¹⁴ Although the incidence of bladder cancer is higher in men than in women (3.1:1 ratio), women disproportionally present with more advanced disease and have a high mortality rate compared to their male counterparts.¹⁵,¹⁶ Studies looking at women evaluated within dedicated urogynecology clinics for MH, with and without symptoms, identified a 0.4% to 1.7% incidence rate of urologic malignancy.¹⁷,¹⁸,¹⁹,²⁰ Despite the low prevalence of bladder cancer in women with MH, risk-stratified referral for investigation is widely recommended.²¹ Women are more likely to experience delay in time to evaluation and time to diagnosis of bladder cancer.¹⁵,²² Although the precise reasons for this remain unknown, this delay may be attributed to repeated testing, initial management of presumed infection, and hesitancy to overinvestigate.²³ Furthermore, some studies report nonadherence to guideline recommendations for cystoscopy and upper tract imaging in up to 20% of female patients.²⁰

Initial evaluation for MH should incorporate careful history and physical examination. Presence of lower urinary tract symptoms, such as urinary frequency, dysuria, and urgency may reflect urinary tract infection. Obstructive pathology may be indicated with hesitancy, incomplete emptying, and reduced urinary flow. Flank or abdominal pain favors potential urolithiasis, trauma, or pyelonephritis. History of risk factors for urologic malignancy should be carefully considered, with smoking history and increased age as the greatest risk factors (Table 39.2). Use of anticoagulation or antiplatelet agents does not exclude a patient from requiring further evaluation.

Physical examination should include abdominal and urogenital examination as well as blood pressure assessment. Speculum examination can be used to rule out vaginal, cervical, and uterine sources of MH. Laboratory investigations include serum creatinine, urea and glomerular filtration rate, and urinalysis to assess for potential renal parenchymal disease. Evaluation of urinary cytology has a high sensitivity in patients with high-grade urothelial cancer and may be used as an adjunct to cystoscopy and radiologic evaluation. Negative cytology, however, does not exclude the possibility of malignancy due to low sensitivity in detection of lowgrade tumors.²⁵ Furthermore, cytologic evaluation can be impaired in the presence of urinary tract infection and urolithiasis. Full diagnostic workup for MH should include radiologic and cystoscopic assessment of both the upper and lower urinary tract, respectively, with referral to urologic services.