Cystitis is a general term describing inflammation of the urinary bladder. Hemorrhagic cystitis (HC) is a severe and specific form of this condition, marked by significant blood loss. The defining symptom is the presence of blood in the urine, known as hematuria, which can range from microscopic traces to visible, heavy bleeding. HC is a serious medical complication most often linked to specific cancer treatments.
Defining Hemorrhagic Cystitis
Hemorrhagic cystitis is characterized by inflammation and damage to the bladder’s inner lining, the urothelium. This damage extends to underlying blood vessels, causing them to rupture and bleed into the bladder cavity. The resulting blood loss is termed gross hematuria when it is visible, causing urine to appear pink, red, or brown. Bleeding severity varies, but profuse cases can lead to the formation of blood clots that obstruct the normal flow of urine. This condition requires specialized medical attention because it presents a risk of anemia or kidney damage if not managed promptly.
Primary Causes and Risk Factors
The primary causes of hemorrhagic cystitis are typically non-infectious, arising mainly as a complication of medical therapies used in cancer treatment. The most common drug-related triggers are the chemotherapy agents cyclophosphamide and ifosfamide, which belong to the oxazaphosphorines class. As the body processes these medications, a toxic metabolite called acrolein is produced and concentrated in the urine. Acrolein is highly irritative and directly damages the urothelium, causing cell death and intense inflammation. This cellular damage exposes the bladder’s blood vessels, leading to the characteristic bleeding.
Radiation therapy directed at the pelvic region for cancers (such as prostate or cervical cancer) is another significant cause. Radiation-induced HC can occur acutely during treatment or, more commonly, months to years later as a late-onset effect. The radiation damages small blood vessels in the bladder wall, resulting in radiation vasculitis that limits blood flow and causes tissue ischemia.
Infectious agents can also trigger hemorrhagic cystitis, particularly in individuals with weakened immune systems, such as transplant recipients. Viral infections are the most frequent culprits, with Adenovirus and the BK Polyomavirus being common examples. These viruses directly infect the bladder lining, causing inflammation and bleeding.
Recognizing the Signs
The most obvious sign of hemorrhagic cystitis is hematuria, which patients may notice as a change in urine color. This visible bleeding can be intermittent or constant, sometimes forming clots that cause significant pain and obstruction. Patients typically experience lower urinary tract symptoms similar to a severe urinary tract infection. These symptoms include dysuria (a painful or burning sensation during urination), a frequent and urgent need to pass urine, and discomfort in the lower abdomen or pelvis.
The clinical presentation can range from a mild case with only microscopic blood to a severe, life-threatening hemorrhage. Severe cases involve large blood clots that can completely block the urethra, making urination impossible, which is a medical emergency requiring immediate intervention. Persistent blood loss can also lead to anemia and severe fatigue.
Treatment and Management Strategies
The management of hemorrhagic cystitis focuses on aggressive supportive care, stopping the bleeding, and treating the underlying cause. Initial acute treatment involves aggressive hydration, often through intravenous fluids, to increase urine output and flush the bladder. Pain management is also a priority to alleviate discomfort caused by inflammation and bladder spasms.
For severe bleeding where blood clots are obstructing the bladder, continuous bladder irrigation is performed. This involves inserting a catheter to flush the bladder continuously with sterile fluid, washing out the clots and debris. If conservative measures fail, medications can be instilled directly into the bladder, such as formalin or alum, to cauterize the bleeding vessels.
Prevention is a primary strategy for patients receiving high-risk chemotherapy agents like cyclophosphamide and ifosfamide. The protective drug Mesna is mandatory in these regimens; it works by neutralizing the toxic metabolite acrolein. Mesna is filtered by the kidneys and excreted into the urine, where it chemically binds to acrolein to form a non-toxic compound that is safely passed from the body.
For radiation-induced hemorrhagic cystitis that does not respond to initial therapies, advanced interventions may be considered. Hyperbaric oxygen therapy (HBOT) is an effective non-invasive option for chronic radiation injury, as it promotes healing. HBOT involves breathing pure oxygen in a pressurized chamber, increasing oxygen concentration in damaged tissues to encourage new blood vessel growth and accelerate tissue repair.