What is the appropriate diagnostic and treatment approach for a patient with hematuria (presence of blood in urine) and leukocytes (white blood cells) in urine, considering factors such as age, sex, and existing medical conditions?

Blood and Leukocytes in Urine: Diagnostic and Treatment Approach

The presence of both blood and leukocytes in urine requires immediate confirmation with microscopic urinalysis (≥3 RBCs/HPF) and urine culture to differentiate between urinary tract infection and more serious urologic or glomerular pathology—never treat empirically without this confirmation, as hematuria carries up to a 40% malignancy risk in high-risk populations. 1, 2

Initial Confirmation and Risk Stratification

Confirm true hematuria first:

• Dipstick positivity has only 65-99% specificity and requires microscopic confirmation showing ≥3 RBCs per high-power field on at least two of three properly collected clean-catch midstream specimens 1, 3
• Exclude pseudohematuria from menstruation, vigorous exercise, or medications that color urine 1, 3
• The combination of leukocytes and blood suggests either urinary tract infection or inflammatory urologic/glomerular disease 4, 5

Obtain urine culture before any antibiotics:

• White blood cells in urine have 62.7% sensitivity and 100% specificity for culture-proven UTI 6
• If UTI is confirmed by culture, treat appropriately and repeat urinalysis 6 weeks after treatment completion to confirm hematuria resolution 3
• Critical pitfall: If hematuria persists after documented UTI treatment, this effectively rules out simple infection and mandates full urologic evaluation—do not prescribe additional antibiotics 1

Risk-Based Evaluation Algorithm

High-risk features requiring immediate complete urologic workup (cystoscopy + CT urography): 1, 2, 3

• Any episode of gross hematuria (30-40% malignancy risk)
• Age ≥60 years (males) or ≥60 years (females)
• Smoking history >30 pack-years

• 25 RBCs/HPF on microscopy

• History of prior gross hematuria
• Occupational exposure to benzenes or aromatic amines
• Irritative voiding symptoms without infection

Intermediate-risk features (shared decision-making for cystoscopy/imaging): 1, 3

• Males age 40-59 years or females age 50-59 years
• Smoking history 10-30 pack-years
• 11-25 RBCs/HPF

Low-risk features (may defer imaging, but close follow-up mandatory): 1, 3

• Females <50 years or males <40 years
• Never smoker or <10 pack-years
• 3-10 RBCs/HPF
• No additional risk factors

Distinguishing Glomerular from Urologic Sources

Examine urinary sediment for glomerular indicators: 1, 2, 3

• Tea-colored or cola-colored urine (not bright red) suggests glomerular origin
• Dysmorphic RBCs >80% indicates glomerular bleeding
• Red blood cell casts are pathognomonic for glomerular disease
• Significant proteinuria (>500 mg/24 hours or protein-to-creatinine ratio >0.2 g/g)

If glomerular features present: 1, 3

• Measure serum creatinine, BUN, complete metabolic panel
• Check complement levels (C3, C4) for post-infectious glomerulonephritis or lupus
• Consider ANA and ANCA if vasculitis suspected
• Refer to nephrology immediately while still completing urologic evaluation—glomerular disease does not exclude concurrent malignancy 1, 3

Complete Urologic Evaluation for Non-Glomerular Hematuria

Upper tract imaging: 1, 2, 3

• Multiphasic CT urography is the preferred modality for detecting renal cell carcinoma, transitional cell carcinoma, and urolithiasis
• Must include unenhanced, nephrographic, and excretory phases
• If CT contraindicated (renal insufficiency, contrast allergy), use MR urography or renal ultrasound with retrograde pyelography

Lower tract evaluation: 1, 2

• Flexible cystoscopy is mandatory for all high-risk patients and most intermediate-risk patients
• Flexible cystoscopy causes less pain and has equivalent or superior diagnostic accuracy compared to rigid cystoscopy
• Voided urine cytology should be obtained in high-risk patients to detect high-grade urothelial carcinomas

Laboratory evaluation: 1, 3

• Serum creatinine to assess renal function
• Complete urinalysis with microscopy
• Urine culture if not already obtained

Critical Pitfalls to Avoid

Never attribute hematuria to anticoagulation or antiplatelet therapy: 1, 2, 3

• These medications may unmask underlying pathology but do not cause hematuria
• Evaluation should proceed identically regardless of anticoagulation status
• Malignancy risk is similar in anticoagulated and non-anticoagulated patients

Never ignore gross hematuria, even if self-limited: 1, 2

• 30-40% association with malignancy mandates urgent urologic referral
• Hematuria can precede bladder cancer diagnosis by many years

Do not treat asymptomatic bacteriuria with pyuria: 1

• Asymptomatic bacteriuria should not be treated in the general adult population
• Treatment leads to early recurrence with more resistant bacterial strains and increases risk of Clostridioides difficile infection
• Hematuria requires evaluation for urologic causes, not antibiotic treatment

Follow-Up Protocol for Negative Initial Evaluation

If complete workup is negative but hematuria persists: 1, 3

• Repeat urinalysis at 6,12,24, and 36 months
• Monitor blood pressure at each visit
• Consider repeat complete evaluation within 3-5 years for persistent hematuria in high-risk patients
• After two consecutive negative annual urinalyses, no further testing for asymptomatic microhematuria is necessary

Immediate re-evaluation warranted if: 1, 3

• Gross hematuria develops
• Significant increase in degree of microscopic hematuria
• New urologic symptoms appear (flank pain, dysuria, irritative voiding)
• Development of hypertension, proteinuria, or evidence of glomerular bleeding

Age-Specific Considerations

Pediatric patients: 7, 1

• Children with isolated microscopic hematuria without proteinuria or dysmorphic RBCs do not require imaging
• Renal ultrasound is appropriate first-line imaging for gross hematuria to exclude nephrolithiasis and anatomic abnormalities
• CT is not appropriate in initial evaluation of isolated nonpainful, nontraumatic hematuria in children
• Glomerulonephritis and congenital anomalies are most common causes in children

Elderly patients (>60 years): 1, 2

• Automatically classified as high-risk requiring cystoscopy and CT urography
• Malignancy prevalence can be as high as 21% in older men with asymptomatic microscopic hematuria
• Long-term surveillance is essential as hematuria can precede cancer diagnosis by years