What Is Hemorrhagic Cystitis?

Hemorrhagic cystitis is a bladder condition that causes pain and hematuria (blood in the urine). It can develop as a complication of cancer treatment, including chemotherapy and radiation, or it can result from bladder infections. Prompt treatment, such as medication and bladder irrigation, can help manage pain and prevent lasting bladder damage.

Diagram of human kidneys and bladder
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Symptoms of Hemorrhagic Cystitis

The bleeding, pain, and other symptoms of hemorrhagic cystitis are similar to those of a serious urinary tract infection (UTI). One aspect that sets hemorrhagic cystitis apart from most 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 a combination of the severity of bleeding and abdominal pain.

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 is usually caused by chemotherapy and radiation. Hemorrhagic cystitis caused by bladder infections tends to be acute and may resolve more easily.

Chemotherapy

The chemotherapy medications most often associated with hemorrhagic cystitis are alkylating agents.

  • Cyclophosphamide is used primarily to treat leukemia or lymphoma or autoimmune disorders, such as severe forms of lupus.
  • Ifex (ifosfamide) is used to treat sarcomas, leukemia, and lymphoma.

When the body breaks down either of these drugs, acrolein, a byproduct, is produced, Acrolein is filtered out of the blood by the kidneys and becomes highly concentrated in the urine that's stored inside the bladder. This irritates the lining of the bladder, leading to inflammation, pain, and 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 usually develops within one or two days of 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
  • Doxorubicin, an intravenous (IV, in a vein) injection
  • Bleomycin, an injection that's used in cancer treatment
  • Thiotepa (Tepadina), an IV 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 treatment of uterine, cervical, bladder, or prostate cancers.

Hematuria may develop during treatment or it may develop months or years later due to ischemia (insufficient blood supply) in the mucosal lining of the bladder that causes ulceration and bleeding. The damage may also lead to the growth of new vessels in damaged areas—the vessels can be fragile and may 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

Having an impaired immune system puts you at a higher risk of developing hemorrhagic cystitis from infections, particularly if you are recovering from an organ transplant or bone marrow or stem cell transplant. When the immune system is compromised, which is a common effect of chemical immunosuppression after a transplant, 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 include:

  • 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:

  • Impaired immune system makes 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 healthcare provider right away. It will be important to get a definitive diagnosis.

Your healthcare provider will first take a medical history. This includes details about any cancer treatment or a transplant procedure you've had, as well as a list of all medications you're taking.

  • You will be asked to provide a urine sample, which can identify a urinary tract infection (UTI). Your blood will be tested for problems like anemia.
  • Your healthcare provider 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 identify any blood clots.
  • Your healthcare provider may also want to perform a cystoscopy, which involves insertion of a small tube with a camera through your urethra to more closely examine the lining of your bladder. Cystoscopy can also be used to obtain a biopsy sample or for treating areas of bleeding with a laser (fulguration).

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 narrowing or blockage of the urinary tract.

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

  • Careful observation
  • Hydration, which may include intravenous fluids
  • 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: A piece of the small intestine is used to create a cutaneous ureterostomy, which is a newly formed urethra that extends through a stoma (hole in the abdomen)
  • Vesical artery embolization: Closing 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 at high risk for developing hemorrhagic cystitis, your healthcare team will likely take measures to try to prevent this complication.

Prevention often is focused on decreasing the amount of time the lining of your bladder is exposed to acrolein or other irritants.

Your healthcare providers may:

  • Administer MESNA (2-Mercaptoethanesulfonate sodium), a medication that helps protect your bladder from the effects of acrolein. This medication is given IV, either separately or along with your chemotherapy medication.
  • Give you lots of IV fluids to help the chemotherapeutic medications and their byproducts pass through your bladder more quickly
  • Schedule 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 chemotherapeutic medications and their byproducts from your bladder
  • Insert a urinary catheter so the chemotherapeutic and their byproducts are continuously removed from your bladder before they have 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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