Microhematuria: ≥ 3 RBC/HPF; not visible to naked eye

Gross hematuria: blood in urine visible to naked eye

Etiologies

• Glomerular - IgA nephropathy (most common; benign), thin glomerular basement membrane disease, Alport's
• Upper tract - stones, pyelo, RCC, TCC, obstruction
• Lower tract - UTI, BPH, strenuous exercise, TCC, instrumentation
• Spurious - e.g. menses, inflammation from balanitis

Risk factors for malignancy (TCC, RCC) with hematuria:

• old age, male, tobacco, chemical exposure, pelvic radiation, irritative voiding sx, prior urologic disease
• Malignancy found in 4% of microscopic hematuria, 23% of gross hematuria on initial evaluation

Urine contains urokinase (promotes clot lysis) - can cause persistent urinary bleeding

• Evaluate for etiology of hematuria (above)
• Medications causing red urine: pyridium, macrobid, bactrim, rifampin, ibuprofen, phenytoin, methyldopa/levodopa, chloroquine, phenacetin, quinine

Microhematuria

• Confirm with microscopy (> 3 RBCs/HPF), not dipstick alone (single positive microscopy sufficient to prompt evaluation)
  • Freshly voided, clean catch, midstream specimen
  • Dipstick: 95% sensitive, 75% specific (false positives: myoglobin, betadine; false negatives: vitamin C)
  • Red cell casts, proteinuria suggest glomerular bleeding - refer to nephrologist (but continue urologic workup)
• If benign etiology is identified and treated (UTI, stone, etc.) repeat UA to document resolution of hematuria

New AUA guidelines (2025) stratify workup based on risk for urothelial cancer

• Previously cysto + CT IVP in all patients (unless < 35 and asymptomatic, then no cysto)
  • Finds malignancy in 4%, no etiology in 43% on initial evaluation
  • < 3% develop malignancy after negative initial evaluation

• *Additional UCC risk factors:
  • Irritative LUTS
  • Pelvic radiation
  • Hx cyclophoshamide/ifosfamide chemo
  • FHx of UCC or Lynch syndrome
  • Occupational exposure to benzene, aromatics
  • Chronic indwelling foreign body in urinary tract
• No urine cytology on initial evaluation
  • Consider if recurrent microhematuria + irritative LUTS/risk factors
• If negative workup and another negative UA within 12 months, can stop monitoring

Gross hematuria

• If in setting of trauma or culture-documented UTI, treat and then follow up UA
• Otherwise, CT IVP and cystoscopy
  • Finds malignancy in 23%, no etiology in 8% on initial evaluation
  • 18% develop malignancy after negative initial evaluation
• Negative workup: yearly UA/micro; stop if negative x 2. Repeat work-up if persists > 3-5 yrs

Hemorrhagic cystitis (intractable bleeding from bladder)

• Hemorrhagic cystitis: a challenge to the urologist (review)
• Etiologies
  • Infection (bacterial; BK virus, adenovirus)
  • Chemotherapy (cyclophosphamide, ifosfamide). Acrolein metabolite causes bladder sloughing; Mesna binds acrolein and can be protective
  • Radiation
  • Malignancy, trauma, post-surgical (e.g. TURP)
  • Prostatic (BPH, prostate ca) - add finasteride for hematuria from BPH (decreases prostate hypervascularity)
• First tier
  • Treat underlying causes; stop anticoagulants
    • If post-surgical, can place Foley on traction to help balloon tamponade the bleed
  • 22Fr 6 eye - irrigate all clots, consider 3-way catheter for CBI, encourage hydration/diuresis
    • Hydrogen peroxide can help resolve clot burden. 1:5 mixture of 3% hydrogen peroxide:normal saline. Instill for 3-5 min, then irrigate.
• Second tier
  • Alum 1% - 50 g alum in 5 L bag; irrigate at 200-300 cc/hr. 66-100% success rate.
    • Astringent - causes protein precipitation and clotting.
    • Not painful, does not require anesthesia
    • Can be given if VUR present.
    • Absorbed systemically and excreted renally - avoid if renal failure; toxicity includes mental status changes
  • Amicar (aminocaproic acid) - 200 mg/L in NS, irrigate x 24 hrs after hematuria resolves. Must evacuate all clots first otherwise clots will harden
    • Inhibits plasminogen activators (e.g. urokinase) to stop fibrinolysis/hemorrhage
    • Contraindicated for thrombosis risk, DIC, upper tract bleeding
    • Not systemically absorbed from intravesical use, but systemic toxicity includes rhabdomyolysis
  • Silver nitrate (similar action/side effects to formalin) - 0.5-1% solution instilled for 10-20 min
    • Causes chemical coagulation
    • Painful
    • Can precipitate and cause upper tract obstruction - contraindicated if extravasation/reflux (get pre-tx cysto)
• Third tier
  • Hyperbaric oxygen
    • Promotes neovascularization and wound healing
    • Indicated for prior radiation or cyclophosphamide exposure
    • Contraindicated if hx cisplatin/doxorubicin, pneumothorax, viral infxn
  • Formalin - Highly effective but toxic and requires anesthesia. Instill ~ 300cc of 1-2% for 10-15 min. Catheter on light traction to prevent urethral exposure
    • Causes cellular protein precipication and capillary occlusion
    • Painful - requires general/spinal anesthesia
    • Can cause bladder fibrosis, ureteral stricturing - contraindicated if extravasation/reflux (get pre-tx cysto)
• If unstable or intractable - angioembolization of anterior branch of internal iliac artery
• Last resort - cystectomy and urinary diversion