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

Major causes of hematuria in relation to the age at which they usually occur (horizontal axis), transience or persistence (vertical axis), and frequency (blue implies more frequent).

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

Microhematuria

• Confirm positive dipstick with microscopy (> 3 RBCs/HPF)
• Single positive microscopy sufficient to prompt evaluation [cite AUA guideline]
• 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 (2020) 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