What are the causes of hemorrhagic cystitis?

Causes of Hemorrhagic Cystitis

Hemorrhagic cystitis is primarily caused by radiation therapy, chemotherapeutic agents (particularly cyclophosphamide), viral infections, and bacterial infections, with radiation and cyclophosphamide being the most common etiologies. 1, 2, 3

Major Etiologies

1. Treatment-Related Causes

• Chemotherapy:

  • Oxaphosphorines: Cyclophosphamide and ifosfamide are the most frequent chemical causes 3
  • Mechanism: Metabolites (particularly acrolein) cause direct damage to bladder epithelium 4
  • Risk increases with higher doses and longer duration of treatment
  • Can occur with both short-term and long-term use 4

• Radiation Therapy:

  • Common complication of pelvic radiation for gynecological malignancies 1
  • Mechanism: Vascular endothelial cell damage leading to edema, cell death, and fibrosis 1
  • Can develop with latency period of 1-25 years after treatment 1
  • Incidence: 5-9% of patients receiving pelvic radiation 1

2. Infectious Causes

• Viral:

  • BK virus, adenovirus, CMV (particularly in immunocompromised hosts)
  • More common in transplant recipients and immunosuppressed patients 2

• Bacterial:

  • Urinary tract infections with bacterial colonization
  • Can cause inflammation and bleeding of bladder mucosa 1
  • Requires urine culture for confirmation 1

3. Other Causes

• Trauma:

  • Bladder instrumentation or catheterization
  • Recent urologic procedures 1

• Systemic Diseases:

  • Autoimmune conditions
  • Coagulopathies or bleeding disorders 3

• Idiopathic:

  • No identifiable cause despite thorough evaluation 3

Risk Factors

For Radiation-Induced Hemorrhagic Cystitis:

• History of abdominal surgery
• Pelvic inflammatory disease
• Hypertension
• Diabetes mellitus
• Smoking
• Older age
• Obesity/overweight 1

For Chemotherapy-Induced Hemorrhagic Cystitis:

• High doses of cyclophosphamide
• Inadequate hydration during treatment
• Pre-existing bladder conditions
• Urinary tract obstructions 4

Clinical Presentation and Diagnosis

Presentation ranges from microscopic hematuria to gross hematuria with clots and urinary retention. Associated symptoms may include:

• Dysuria
• Urinary frequency
• Nocturia
• Hesitancy
• Suprapubic pain 1

Diagnostic workup should include:

• Urinalysis with microscopy (≥3 RBCs per HPF confirms hematuria) 1
• Urine culture to rule out infection
• Imaging studies (ultrasound, CT urography, or MRI) to evaluate upper and lower urinary tract 1
• Cystoscopy to directly visualize bladder mucosa 1

Prevention and Management

Prevention:

• For cyclophosphamide therapy:

  • Aggressive hydration with forced diuresis
  • Frequent bladder emptying
  • Mesna administration to prevent bladder toxicity 4

• For radiation therapy:

  • IMRT techniques to reduce bladder exposure
  • Maintaining bladder dose D2cm³ ≤80 Gy EQD2 1

Treatment:

• Conservative management for mild cases
• Hydration and clot evacuation for moderate cases
• For severe cases:
  • Endoscopic fulguration
  • Bladder irrigation with various substances
  • Hyperbaric oxygen therapy 1, 5
  • Arterial embolization for refractory cases
  • Surgery (including cystectomy) as last resort 3

Hemorrhagic cystitis represents a significant clinical challenge with substantial morbidity and potential mortality. Early recognition of risk factors and prompt implementation of preventive measures are essential to reduce its incidence and severity.