What Is Hemorrhagic Cystitis?

Hemorrhagic cystitis is a condition caused by damage to the blood vessels in the mucosal lining of the bladder. It causes acute or chronic urinary tract symptoms such as pain, inflammation, and hematuria (blood in the urine). The condition commonly is a complication of cancer treatment—chemotherapy drugs, radiation, or both.

Hemorrhagic cystitis also can result from viral or bacterial infections, especially among people who are immunocompromised—adding an additional risk of hemorrhagic cystitis for those undergoing chemotherapy. Prompt treatments, such as medications and bladder irrigation methods, can help to manage pain and prevent lasting damage to the bladder.

Diagram of human kidneys and bladder
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Symptoms of Hemorrhagic Cystitis

The bleeding, pain, and other symptoms of hemorrhagic cystitis are not unlike those of a serious urinary tract infection (UTI). One aspect that sets hemorrhagic cystitis apart from garden-variety UTIs is that the severity of the condition is graded based on the amount of bleeding.

Hemorrhagic Cystitis Grading
Grade 1 Microscopic bleeding
Grade 2 Visible bleeding
Grade 3 Visible bleeding with small clots
Grade 4 Visible bleeding with large clots that block the urinary tract and require removal

It also may be rated as mild, moderate, or severe based on both bleeding and another key symptom—abdominal pain.

Other symptoms of hemorrhagic cystitis include:

  • Dysuria (pain or burning when passing urine)
  • Feeling unable to empty the bladder
  • Loss of bladder control (incontinence)
  • Urinary frequency or an urgent need to empty the bladder
  • Getting up multiple times a night to urinate
  • Fatigue due to anemia
  • Vague pain in the lower abdomen above the pubic area of the pelvic bone

Causes and Risk Factors

Chronic severe hemorrhagic cystitis typically is caused by chemotherapy and radiation. Viral or bacterial infections can also cause hemorrhagic cystitis, but these cases tend to be acute and may resolve more easily than those caused by cancer treatments.

Chemotherapy

The chemotherapy medications most often associated with hemorrhagic cystitis are the alkylating agents cyclophosphamide injection and Ifex (ifosfamide injection)—used primarily to treat blood and marrow cancers such as leukemia or lymphoma. Cyclophosphamide is sometimes used to treat autoimmune disorders, such as severe forms of lupus, and can also cause hemorrhagic cystitis in these patients.

When the body breaks down either of these drugs, a byproduct called acrolein is produced, which is filtered out of the blood by the kidneys and becomes highly concentrated in the urine stored inside the bladder. This irritates the lining of the bladder, leading to the discomfort of cystitis as well as ulcers that can cause serious bleeding.

The incidence of hemorrhagic cystitis associated with chemotherapy varies widely across studies, ranging from less than 10% to 35%. It can develop weeks or months after treatment. Research has found that it occurs in about 20% of people undergoing bone marrow transplantation and receiving high-dose cyclophosphamide. Ifosfamide has been associated with a higher incidence of hemorrhagic cystitis in some studies, possibly because higher doses tend to be used.

Treatment for bladder cancer that includes both cyclophosphamide and bacillus Calmette-Guérin can also cause hemorrhagic cystitis.

Other chemotherapy agents associated with hemorrhagic cystitis include:

  • Temozolomide (Temodar), which comes in a capsule taken by mouth
  • Busulfan (Myleran), which comes as a tablet taken by mouth
  • Bleomycin, an antibiotic injection that's only used in cancer treatment
  • Doxorubicin, an intravenous injection
  • Thiotepa (Tepadina), an intravenous injection or an injection directly into the bladder by tube or catheter

Radiation Therapy

Radiation therapy also is linked with hemorrhagic cystitis in cancer patients, especially those receiving pelvic radiation, such as for uterine, cervical, bladder, or prostate cancers.

Hematuria may develop during treatment or many months or years later due to damage to the bladder that leads to ischemia (insufficient blood supply) in the mucosal lining, causing ulceration and bleeding. There may also be growth of new vessels in damaged areas that are fragile and leak easily.

Infection

Any number of infections have been linked to hemorrhagic cystitis, from common viral infections to parasitic diseases.

Viruses associated with hemorrhagic cystitis include:

Among the bacterial organisms known to cause hemorrhagic cystitis are:

  • Escherichia coli (E. coli)
  • Staphylococcus saprophyticus (S. saprophyticus)
  • Proteus mirabilis (P. mirabilis)
  • Klebsiella

While rare, hemorrhagic cystitis may develop as a result of parasitic diseases such as schistosomiasis, a disease caused by parasitic worms, or Echinococcosis, caused by a parasitic tapeworm, or fungal infections, such as from Candida albicans or Cryptococcus neoformans.

Other Causes

People with lowered immune systems are at higher risk of hemorrhagic cystitis from infections, particularly those who are recovering from an organ transplant or bone marrow or stem cell transplant. When the immune system is compromised, including chemical immunosuppression after transplants, infections can thrive or get reactivated, leading to cystitis.

In some cases, occupational or environmental exposure to certain pesticides or chemicals used in manufacturing can contribute to hemorrhagic cystitis. These includes:

  • Aniline dyes
  • Toluidine
  • Chlorodimeform
  • Ether

Risk Factors 

There are a few reasons adults or children with leukemia or lymphoma might be more prone to getting hemorrhagic cystitis:

  • Lowered immune system making you more susceptible to frequent urinary tract infections or viruses
  • Frequent use of antibiotics
  • Low platelet counts (thrombocytopenia)
  • Male gender
  • Being older than 5

Diagnosis

If you develop symptoms of hemorrhagic cystitis, see your doctor right away. It will be important to get a definitive diagnosis of the condition as well as pin down what has caused it in order to effectively treat it.

To do so, your doctor will first take a medical history. They will be especially interested in knowing if you have a history of cancer treatment or a transplant procedure, as well as about any and all medications you're taking.

You will be asked to provide a urine sample, which can rule out a urinary tract infection (UTI). Your blood will be tested as well for anemia.

Your doctor also may order imaging tests such as ultrasonography, computed tomography (CT scan), or magnetic resonance imaging (MRI) to examine your bladder and upper urinary tract. These tests can help determine the severity of inflammation and measure the size and number of clots.

Your physician may also want to perform a cystoscopy, which involves inserting a small tube with a camera through the urethra to more closely examine the lining of the bladder. Cystoscopy can also be used for laser (fulguration) of bleeding sites or to biopsy suspicious areas.

Treatment 

Once diagnosed, it's vital for hemorrhagic cystitis to be treated promptly. The condition can lead to severe blood loss and permanent bladder damage. Open ulcers in the bladder can provide a portal for bacteria to pass into your bloodstream and could put you at risk for urosepsis, a severe and life-threatening blood infection that originates in the urinary tract. It may also lead to permanent scarring of the lining of the bladder, which could cause a narrowing or blockage of the urinary tract.

Treatment will depend on the cause and the severity of bleeding:

  • Hydration, which may include intravenous fluids, and careful observation
  • Pain medication
  • Medication to relax bladder muscles
  • Platelet transfusions to help control bleeding
  • Blood transfusions if the bleeding has caused anemia
  • Antibiotic, antiviral, or antifungal therapy if the cause of the cystitis is infectious in nature
  • Irrigation of the bladder with a saline solution via catheter to prevent or remove clots
  • Medications to control bleeding
  • Intravesical therapy in which medications are put into the bladder decrease or stop bleeding and pain
  • Hyperbaric oxygen therapy, or breathing 100% oxygen in a pressurized room or through a tube, to try to promote tissue healing after radiation

In chronic cases that don't respond to other treatments, known as refractory hemorrhagic cystitis, surgery may be recommended. This may include any of the following:

  • Open cystotomy (surgical incision into the bladder) and temporary packing of the bladder with gauze and topical medications to staunch bleeding
  • Permanent urinary diversion (such as by ileal conduit, or using a piece of the small intestine to create a new tube, or cutaneous ureterostomy, a procedure that detaches ureters from the bladder) through a hole in the abdomen called a stoma
  • Vesical artery embolization, using surgical methods to block some of the arteries involved in the bleeding
  • Cystectomy, removal of the bladder

Although there are successful case studies, major surgical procedures for hemorrhagic cystitis are considered a last resort because they have a high risk of complications and cause permanent anatomical changes.

Prevention 

If you are being treated with chemotherapy, especially if you've been identified as being high risk for developing this complication, your healthcare team will likely take measures to try to prevent hemorrhagic cystitis. Most work by decreasing the amount of time the lining of your bladder is exposed to acrolein or other irritants. Your doctors may:

  • Administer a medication called MESNA (2-Mercaptoethanesulfonate sodium), which helps protect your bladder from the effects of acrolein. This medication is given intravenously, either separately or along with your chemotherapy medication.
  • Give lots of intravenous fluids to help the chemo pass through your bladder more quickly
  • Try to give your chemotherapy early in the day so you have an opportunity to clear it from your bladder before resting for the night
  • Encourage you to try to urinate at least every hour
  • Administer diuretics, which help keep urine flowing to clear the chemo from your bladder
  • Insert a urinary catheter so the chemo is continuously removed from your bladder before it has the opportunity to cause ulceration

A Word From Verywell

Hemorrhagic cystitis can be serious and painful. Fortunately, there are ways to help prevent this condition from occurring and many ways to treat it if it does occur. Speak to your healthcare provider if you have any concerns about upcoming cancer treatments or at the first sign of any urinary symptoms.

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