eMedicine Specialties > Pediatrics: Surgery > Urology

Hemorrhagic Cystitis

Marcos Perez-Brayfield, MD, Consulting Staff, HIMA-San Pablo, San Juan, Puerto Rico
Andrew J Kirsch, MD, FAAP, FACS, Clinical Professor of Urology, Emory University School of Medicine, Children's Healthcare of Atlanta; President, Georgia Urology, PA

Updated: Sep 18, 2009

Introduction

Background

Hemorrhagic cystitis (HC) is a common condition observed in pediatric oncology patients and is a cause of great morbidity and potential mortality in this already compromised group of patients. Hemorrhagic cystitis is defined by lower urinary tract symptoms that include hematuria and irritative voiding symptoms. It results from damage to the bladder transitional epithelium and blood vessels by toxins, viruses, radiation, drugs, or disease.

The pediatric oncology patient may be exposed to all of these factors. Patients who undergo bone marrow transplantation frequently have hemorrhagic cystitis because most are exposed to cyclophosphamide, total-body irradiation, or both. Patients with malignancies and those undergoing chemotherapy are often immunocompromised and are at high risk of acquiring bacterial and viral infections that can cause hemorrhagic cystitis.

Pathophysiology

Hemorrhagic cystitis results from damage to the bladder transitional epithelium and blood vessels by toxins, viruses, radiation, drugs, or disease. Reported causative infectious agents for hemorrhagic cystitis include Escherichia coli; adenoviruses 7, 11, 21, and 35, papovavirus; and influenza A.

Cyclophosphamide is the most common cause of hemorrhagic cystitis in the pediatric oncology population. Urologic adverse effects of cyclophosphamide include frequency, dysuria, urgency, suprapubic discomfort, and both microscopic and gross hematuria. In rare cases, mucosal necrosis, bladder fibrosis, contracture, vesicoureteral reflux (VUR), and tumor formation occur.

Urologic adverse effects are observed in 2%-40% of patients who have undergone cyclophosphamide chemotherapy. Hemorrhagic cystitis secondary to cyclophosphamide therapy appears to be dose-related and most prevalent in patients who are dehydrated and those receiving intravenous treatment. The urotoxicity observed with cyclophosphamide is due to its liver metabolite acrolein. Although the entire urothelium is at risk of urotoxicity, the bladder, which serves as a reservoir, is most frequently affected because the contact time between acrolein and the urothelium is greatest at this site.

Radiation-induced hemorrhagic cystitis is most common in patients receiving pelvic irradiation. The incidence in the pediatric population is less than that in adults. Hematuria may develop acutely during radiation treatment or months to years later. Mucosal ischemia secondary to radiation injury results from end arteritis that induces hypoxic surface damage, ulceration, and bleeding. Factors that contribute to radiation cystitis include bladder outlet obstruction, infection, previous radiation or surgery, and excessive radiation dosage.

Frequency

United States

Hemorrhagic cystitis is common among pediatric oncology patients. Patients treated with cyclophosphamide have a 2%-40% incidence of urologic adverse effects. Approximately 10% of patients receiving pelvic radiation develop hemorrhagic cystitis. The incidence in the pediatric population is less than that in adults.

Mortality/Morbidity

Clinically significant morbidity is associated with hemorrhagic cystitis and its treatments. Although uncommon, severe hemorrhagic cystitis refractory to several therapeutic modalities poses a risk of mortality.

Race

Hemorrhagic cystitis has no known racial predilection.

Sex

Hemorrhagic cystitis has no known sexual predilection.

Age

Hemorrhagic cystitis manifests in people of any age.

Clinical

History

Hemorrhagic cystitis (HC) is defined by lower urinary tract symptoms that include hematuria and, usually, gross and irritative voiding symptoms; these include urinary frequency, urgency, and dysuria. A history of new urinary incontinence is frequently noted. Patients with hemorrhagic cystitis are commonly oncology patients who have undergone chemotherapy or radiation therapy. Identify factors that contribute to the development of hemorrhagic cystitis. These include bladder outlet obstruction, infection, previous radiation or surgery, previous chemotherapy treatments, and excessive radiation dosage.

Physical

Patients with hemorrhagic cystitis can present with variable degrees of hematuria, ranging from slightly blood-tinged urine to massive gross hematuria with passing of clots that may cause urinary retention. Patients with this disease may have a distended, tender, palpable bladder. Clot retention is common and can be very painful. Urinary incontinence is frequently observed.

Causes

Hemorrhagic cystitis results from damage to the bladder transitional epithelium and blood vessels by toxins, viruses, irradiation, drugs, or disease. Patients with malignancies and those undergoing chemotherapy are frequently immunocompromised and at high risk of acquiring the bacterial and viral infections responsible for the hemorrhagic cystitis. Reported causative infectious agents for hemorrhagic cystitis include E coli; adenoviruses 7, 11, 21, and 35; papovavirus; and influenza A.

Hemorrhagic cystitis secondary to cyclophosphamide therapy appears to be dose-related and is most prevalent in patients who are dehydrated and those receiving intravenous treatment. The urotoxicity observed with cyclophosphamide is due to its liver metabolite, acrolein. Although the entire urothelium is at risk of urotoxicity, the bladder, as a reservoir, is most frequently affected because the contact time between acrolein and the urothelium is greatest at this site.

Mucosal ischemia secondary to radiation injury results from end arteritis, which induces hypoxic surface damage, ulceration, and bleeding. Factors that contribute to radiation cystitis include bladder outlet obstruction, infection, previous radiation or surgery, and excessive radiation dosage.

  • Cyclophosphamide hemorrhagic cystitis
    • Cyclophosphamide is the most common cause of hemorrhagic cystitis.
    • Urologic adverse effects with cyclophosphamide have an incidence of 2%-40% and include frequency, dysuria, urgency, suprapubic discomfort, and microscopic or gross hematuria. In rare cases, mucosal necrosis, bladder fibrosis, contracture, VUR, and tumor formation may occur.
    • Risk of adverse effects is dose-related (oral >90 g; intravenous >18 g).
    • Risk factors include dehydration and intravenous infusion.
    • The urotoxic metabolite is acrolein. Acrolein is a liver metabolite of cyclophosphamide. The bladder is most frequently affected because of its contact time with this agent.
  • Radiation-induced hemorrhagic cystitis
    • This is most common with pelvic radiation.
    • The incidence in adults is less than that in the pediatric population.
    • Hemorrhagic cystitis may develop acutely or months to years later.
    • Mucosal ischemia secondary to radiation injury results from end arteritis inducing hypoxic surface damage, ulceration, and bleeding.
    • Cystitis is nonspecific.
  • Viral-induced hemorrhagic cystitis
    • BK virus (polyoma virus): It usually subclinically infects most of the population in childhood. Polyoma viruses are known to cause hemorrhagic cystitis in children. It persists indefinitely in the kidney after primary infection. It is reactivated and excreted in the urine in patients with depressed cellular immunity.
    • Adenovirus: The species most commonly isolated is adenovirus type 11, which has a propensity for the urinary tract. It reactivates with profound immunosuppression. It is the most common cause of hemorrhagic cystitis in the healthy child.

Differential Diagnoses

Other Problems to Be Considered

Other causes of gross hematuria should be considered, such as bacterial infection of the bladder, bladder urolithiasis, bleeding caused by a vascular lesion (hemangioma or arteriovenous malformation), urothelial tumor, or interstitial cystitis.

Workup

Laboratory Studies

  • The evaluation of the pediatric oncology patient with hemorrhagic cystitis (HC) includes microbiology, imaging studies, and possibly cystoscopy.
  • In all patients, obtain a CBC count with platelet counts, coagulation studies, and urine cultures for bacteria and virus, and, at a minimum, perform bladder and renal ultrasonography.
    • If a bacterial infection is documented, voiding cystourethrography (VCUG) should be performed.
    • Oncology patients with pancytopenia can present with bleeding diathesis, including hematuria.
    • Transfusion with platelets or coagulation products aids in the successful treatment of hemorrhagic cystitis.
    • In addition, patients with pancytopenia are immunocompromised and are at high risk for infections, including bacterial and viral cystitis, and, thus, urine culture for these pathogens should be obtained.
    • Results from both the bacterial and viral cultures guide the selection of antibiotic and antiviral therapy.
    • Potential difficulties with the acquisition of urine cultures arises because of the forced hydration and intravesical irrigation used to evacuate clots.
  • Urine studies for viruses include the following:
    • Viral culture
    • Electron microscopy of bladder biopsy specimens
    • Enzyme-linked immunosorbent assay (ELISA)

Imaging Studies

  • Renal bladder ultrasonography is an excellent screening test to rule out many causes of hematuria.
    • Because changes in the urothelium can occur in the urinary upper tract, renal ultrasonography is mandatory to identify hydronephrosis.
    • Dilatation of the upper tract can be secondary to obstruction at the ureteral level or secondary to bladder-wall thickening.
    • Ultrasonography of the bladder also helps to identify blood clots and evaluate their size.
  • In addition, if intravesical sclerotherapy is required, cystography is necessary to determine the bladder capacity and to determine the presence of VUR. The administration of sclerotherapy in the presence of VUR can lead to ureteral fibrosis, obstruction, and possible renal failure, as well as systemic absorption of the agent.
  • CT scanning or MRI is not routinely used in patients with hemorrhagic cystitis.


Diagnosis algorithm. R/O = rule out; US = ultraso...

Diagnosis algorithm. R/O = rule out; US = ultrasonography; VUR = vesicoureteral reflux.


Procedures

  • Cystoscopy
    • Cystoscopy should be considered if the patient has clot retention. Otherwise, cystoscopy contributes little beyond what ultrasonography and VCUG reveal.
    • The endoscopic procedure is performed under general anesthesia in the pediatric population.
    • Attempts to use the largest caliber scope facilitate removal of clots if needed.
    • Most of the time, cystoscopic findings are nonspecific. The bladder appears edematous with multiple punctate hemorrhages. These findings can be isolated to an area of the bladder or diffuse. Areas of active bleeding can be identified.

Histologic Findings

Nonspecific findings include hemorrhage, intense inflammatory infiltrates, chronic inflammation, and fibrosis.

Staging

The staging system for hemorrhagic cystitis has little clinical significance and does not really help in the management of this condition. The main use for the staging system is the standardization of scientific studies on this subject.

  • 0 - No symptoms of bladder irritability or hemorrhage
  • 1 - Microscopic hematuria/frequency/dysuria
  • 2 - Macroscopic hematuria
  • 3 - Macroscopic hematuria with small clots
  • 4 - Massive macroscopic hematuria requiring instrumentation for clot evacuation and/or causing urinary obstruction


Grading of hemorrhagic cystitis.

Grading of hemorrhagic cystitis.


Treatment

Medical Care

The best treatment of hemorrhagic cystitis (HC) is prevention, especially with cyclophosphamide-induced hemorrhagic cystitis. After hemorrhagic cystitis develops, the treatment is the same irrespective of the cause.

The first step in the treatment of hemorrhagic cystitis should be directed toward clot evacuation. Bladder outlet obstruction from clots can lead to urosepsis, bladder rupture, and renal failure. Clot evacuation can be performed by placing a wide-lumen bladder catheter at bedside. The bladder can be irrigated with water or sodium chloride solution. The use of water is preferable because water can help with clot lysis. Care must be taken to not overdistend the bladder and cause a perforation.

After clot evacuation, the patient should be vigorously hydrated using intravenous fluids to keep clots from reforming. If hematuria persists, a 3-way catheter can be inserted, and continuous bladder irrigation with saline can be started. All clots must be removed before continuous irrigation is started to avoid overdistention and potential bladder ruptures.

If clot evacuation is unsuccessful with this approach, the patient should undergo cystoscopy in the operating room with clot evacuation and fulguration of bleeding sites. Some have proposed the use of epsilon aminocaproic acid (Amicar). The problem with aminocaproic acid is that it creates large adhesive clots that are subsequently difficult to remove. With upper tract bleeding, clots due to aminocaproic acid can cause the loss of the respective renal unit, and use in pediatrics is not recommended.

When hematuria persists after the treatments described above, bladder irrigation can be performed with several astringent intravesical agents, including 1% silver nitrate or alum. Alum is an astringent that causes protein precipitation over bleeding sites. The systemic absorption is minimal, even in the presence of VUR. Alum irrigation tends to create large clots that can block the catheter, especially a pediatric-sized catheter. Aluminum levels must be monitored in patients with renal insufficiency because increased levels can cause encephalopathy and acidosis. Parenteral or intravesical prostaglandins are also used to treat hemorrhagic cystitis. Prostaglandins are cytoprotective and have both anti-inflammatory and vasoconstriction properties. They involve no coagulum formation and few side effects and are easy tolerated by the patients.

Formalin intravesical installations are reserved for severe and intractable hemorrhagic cystitis. It hydrolyzes proteins and coagulates superficial bladder mucosal tissue. The most critical factor in the effectiveness of formalin is its concentration. Installation is painful and requires general or regional anesthesia. The concentration used is 2.5-4% for 10-30 minutes. Intraoperative cystography is mandatory to rule out VUR because formalin contact with ureteral tissue leads to fibrosis, obstruction, and necrosis. In the presence of VUR, formalin can be used if occlusion balloon catheters are inserted in both ureters.

Antiviral agents should be added to bladder irrigation when a viral etiology is suspected or confirmed.

Surgical Care

In patients with refractory hemorrhagic cystitis, surgical intervention is warranted. These include percutaneous nephrostomy drainage, selective hypogastric artery embolization, temporary bladder exteriorization with packing of the bladder, ileal conduit diversion, cutaneous ureterostomy, and cystectomy. A few reports describe the use of hyperbaric oxygen, with some success in these difficult cases.1,2

Management of hemorrhagic cystitis. PCN = percuta...

Management of hemorrhagic cystitis. PCN = percutaneous nephrostomy.


  • Hyperbaric oxygen therapy
    • Few reports describe hyperbaric oxygen therapy in the pediatric population.
    • This is an alternative in patients with refractory hemorrhagic cystitis.
    • This treatment is better for radiation-induced hemorrhagic cystitis than for cyclophosphamide-induced hemorrhagic cystitis.
    • Treatment involves 100% oxygenation at 2 atm for 90 minutes 5 times per week. Treatment lasts an average of 40 sessions.
    • Contraindications include active cancer, active viral infection, pneumothorax, treatment with doxorubicin or cisplatin, and ear reconstruction.
  • Nd:YAG laser therapy
    • Few reports describe Nd:YAG laser therapy in the pediatric population.
    • It is used for fulguration.
    • Patients may require several treatments.
    • Laser settings should be no higher than 20 W with a 2-second pulse mode to avoid deep penetration and possible bowel injury.
  • Use of treatment pearls in pediatric patients
    • A catheter with decreased luminal size is needed because of the small urethra in pediatric patients.
    • Consider the use of a suprapubic tube.
    • Water irrigation is best with clot lysis.
    • The pediatric bladder is small; therefore, watch for overdistention, which can lead to rupture.
    • Always keep patients hydrated.
    • All clots must be removed before intravesical irrigations are started.
    • Do not hesitate to go to the operating room with pediatric patients.
    • Use caution with agents that create large clots.
    • If the bleeding cannot be controlled endoscopically, open cystostomy and temporary packing may be considered.
    • With an upper-tract bleed, use of aminocaproic acid is contraindicated.
    • Always perform cystography before formaldehyde therapy to rule out reflux or perforation.

Consultations

Treatment of the patient with hemorrhagic cystitis should be coordinated among urologists, oncologists, and pediatricians.

Diet

No specific diet is indicated.

Activity

Patients with active gross hematuria should limit their activities until it resolves. These patients are hospitalized and on bed rest during their therapeutic interventions.

Medication

Bladder irrigants

Various intravesical agents are used to treat hemorrhagic cystitis (HC). Ongoing assessment of treatment effectiveness is essential for a successful patient outcome. Changing to a different irrigation agent may be necessary.


Formaldehyde (Formalin)

Reserved for severe and intractable hemorrhagic cystitis. Hydrolyzes protein and coagulates superficial bladder mucosal tissue. Most critical factor is to administer proper solution (2.5-4% for 10-30 min). Make 4% solution by mixing buffered formalin 10% 200 mL with sterile water for irrigation 300 mL (total volume, 500 mL).

Dosing

Adult

Bladder irrigation: 4% solution; manually fill bladder to capacity under gravity (catheter <15 cm above symphysis pubis); contact time 10-30 min; painful procedure, and general anesthetic needed

Pediatric

Administer as in adults

Interactions

None reported

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Monitor with intraoperative cystography; before installation, rule out VUR; if present, may proceed after placing occlusive balloon catheters in each ureter; rule out bladder rupture before installation; causes ureteral necrosis, obstruction, and fibrosis


Alum

Indicated for bladder hemorrhage. Consists of aluminum potassium sulfate or aluminum ammonium sulfate and works as astringent that causes protein precipitation in interstitial spaces and cell membranes. Systemic absorption is minimal. May be administered if VUR present.

Dosing

Adult

Bladder irrigation: Extemporaneously prepared as 1% solution; administer as continuous bladder irrigant until bleeding stops

Pediatric

Administer as in adults

Interactions

None reported

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Large blood clots may develop, particularly in pediatric-sized catheters; encephalopathy or acidosis may occur with increased ammonia levels; monitor blood pH and aluminum blood levels


Silver nitrate

Used because of caustic, antiseptic, and astringent qualities. Mixed results observed.

Dosing

Adult

Bladder irrigation: Instill 0.5-1% solution in sterile water into bladder with dwell time of 10-20 min

Pediatric

Administer as in adults

Interactions

None reported

Contraindications

Documented hypersensitivity; broken skin

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Renal failure and anuria reported


Carboprost (Hemabate)

Various prostaglandins studied. Elicits cytoprotective, anti-inflammatory, and vasoconstriction properties and produces no coagulum.

Dosing

Adult

Bladder irrigation: Instill 0.1-0.4% solution; contact 45-60 min

Pediatric

Not established, suggested to administer as in adults

Interactions

Limited data exist; no interactions reported

Contraindications

Documented hypersensitivity; active cardiac, pulmonary, renal, or hepatic disease

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Parenteral administration may cause hypertension, leukocytosis, nausea, vomiting, diarrhea, bronchoconstriction, and pulmonary edema; irrigation may cause flushing or severe bladder spasms

Antidotes

Antidotes are used to manage poisoning and overdose, prevent toxic effects, or treat metabolic disorders in which toxic substances accrue. Mechanisms of action vary and include antagonism, toxin transformation, altered metabolism, chelation, and interactions with directed antibodies.


Mesna (Mesnex)

Also known as 2-mercaptoethane sulfonate. In kidney, mesna disulfide reduced to free mesna. Free mesna has thiol groups that react with acrolein, ifosfamide and cyclophosphamide metabolite considered responsible for urotoxicity. Inactivates acrolein and prevents urothelial toxicity without affecting cytostatic activity. Also directly reacts with 4-hydroxy metabolites, inhibiting breakdown and release of acrolein.

Dosing

Adult

IV mesna dose:
With ifosfamide: 20% of ifosfamide dose; administered 15 min before ifosfamide is started, repeat dose 4 and 8 h later or combined with ifosfamide infusion
With high-dose ifosfamide: 20% of ifosfamide dose; administered 15 min before ifosfamide started, then q3h for 3-6 doses or combined with ifosfamide; total daily mesna doses 60-160% of ifosfamide dose
With cyclophosphamide: 20% of cyclophosphamide dose, administered 15 min before and q3h for 3-4 doses or combined with cyclophosphamide; total daily mesna doses 60-100% of cyclophosphamide dose

Pediatric

Administer as in adults

Interactions

May increase warfarin effects

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Does not prevent hemorrhagic cystitis in all patients (monitor for hematuria in morning before ifosfamide or cyclophosphamide dose); does not prevent or alleviate other toxicities associated with ifosfamide or cyclophosphamide; common adverse effects include hypotension, headache, GI toxicity, and limb pain

Follow-up

Further Inpatient Care

  • The patient should remain well hydrated after the resolution of the hematuria.
  • If a urethral catheter is still in place, pay careful attention to clot formation and urinary tract infections.

Further Outpatient Care

  • Close follow-up is warranted.
  • Previous injury to the bladder by radiation and chemotherapy agents and possible damage to urothelium and bladder muscle by therapeutic agents, such as formalin, require routine evaluation of upper tracts and bladder with renal bladder ultrasonography and additional studies, as needed. Life-long follow-up may be required.
  • The oncology service must be aware of the patient's history of hemorrhagic cystitis (HC) and maximize preventive measures before given any additional oncologic therapy.

Transfer

  • The oncologic patient with hemorrhagic cystitis should be treated at an institution familiar with this condition.
  • The patient with severe hemorrhagic cystitis should be transferred only after his or her condition is stabilized.
  • Only a few facilities offer hyperbaric oxygen therapy. Patients requiring this therapy should be transferred early to these facilities.

Deterrence/Prevention

  • Preventive approaches are available to decrease the urotoxicity related to cyclophosphamide therapy, unlike the other causes of hemorrhagic cystitis.
    • The goal of this strategy is aimed at neutralization or detoxification of acrolein.
    • Most oncology centers recommend vigorous hydration combined with frequent voiding or use of an indwelling bladder catheter to reduce acrolein contact time with the bladder.
  • Two medications, N -acetylcysteine (Mucomyst) and 2-mercaptoethane sulfonate (ie, mesna [Mesnex]), bind to acrolein and form a nonurotoxic compound.
    • Unlike acetylcysteine, mesna specifically binds to acrolein and does not interfere with its therapeutics effects when administered systemically.
    • Routine prophylactic administration of mesna is recommended in patients receiving cyclophosphamide therapy.
  • Discontinuation of cyclophosphamide is mandatory in patients with developing hemorrhagic cystitis because hematuria can subside with this maneuver in most patients.
  • Unlike cyclophosphamide hemorrhagic cystitis, no effective preventive measures are available for radiation-induced hemorrhagic cystitis.

Complications

  • Hemorrhagic cystitis is considered a complication of previous oncologic treatments.
  • Additional complications are related to the agents used to control the bleeding.
  • The specific complications are discussed above.

Prognosis

  • The prognosis in patients with hemorrhagic cystitis is related to successful treatment of their primary oncologic condition.
  • Most patients are successfully treated, with a resolution of hemorrhagic cystitis. However, long-term effects on the bladder may include increased bladder fibrosis, reduced bladder capacity, and upper tract deterioration.
  • Patient with severe hemorrhagic cystitis refractory to medical intervention are at an increased risk for mortality.

Patient Education

  • The physicians treating oncology patients must be aware of the possible preventive measures against hemorrhagic cystitis.
  • Patients at high risk must be educated about the possibility of the development of hemorrhagic cystitis and the need for early intervention.
  • For excellent patient education resources, visit eMedicine's Kidneys and Urinary System Center. Also see eMedicine's patient education article Blood in the Urine.

Miscellaneous

Medicolegal Pitfalls

  • Potential medicolegal problems are present in patients with hemorrhagic cystitis (HC) who are in a fragile condition.
  • Hemorrhagic cystitis is a complication of previous therapy with potential morbidity and mortality.
  • The possibility of developing hemorrhagic cystitis must be addressed with every patient undergoing oncologic treatment.
  • After a patient develops hemorrhagic cystitis, detailed discussion of the treatments, complications, and possible mortality risk should be presented to the patient and/or parents.

Special Concerns

  • Prevention is essential in this condition.
    • Two standard methods of prevention are hyperhydration and mesna administration.
    • Controversial methods include prophylactic bladder irrigation and hourly voiding.
  • Hemorrhagic cystitis is source of great morbidity and mortality.
    • Prevention is the most important factor.
    • Diagnosis and treatment should be prompt.
    • In a few patients, an aggressive approach is warranted to save their lives.

Multimedia

Diagnosis algorithm. R/O = rule out; US = ultraso...

Media file 1: Diagnosis algorithm. R/O = rule out; US = ultrasonography; VUR = vesicoureteral reflux.

Management of hemorrhagic cystitis. PCN = percuta...

Media file 2: Management of hemorrhagic cystitis. PCN = percutaneous nephrostomy.

Grading of hemorrhagic cystitis.

Media file 3: Grading of hemorrhagic cystitis.

References

  1. Corman JM, McClure D, Pritchett R, et al. Treatment of radiation induced hemorrhagic cystitis with hyperbaric oxygen. J Urol. Jun 2003;169(6):2200-2. [Medline].

  2. Del Pizzo JJ, Chew BH, Jacobs SC, Sklar GN. Treatment of radiation induced hemorrhagic cystitis with hyperbaric oxygen: long-term followup. J Urol. Sep 1998;160(3 Pt 1):731-3. [Medline].

  3. Cohen MH, Dagher R, Griebel DJ, et al. U.S. Food and Drug Administration drug approval summaries: imatinib mesylate, mesna tablets, and zoledronic acid. Oncologist. 2002;7(5):393-400. [Medline][Full Text].

  4. deVries CR, Freiha FS. Hemorrhagic cystitis: a review. J Urol. Jan 1990;143(1):1-9. [Medline].

  5. Dewan AK, Mohan GM, Ravi R. Intravesical formalin for hemorrhagic cystitis following irradiation of cancer of the cervix. Int J Gynaecol Obstet. Aug 1993;42(2):131-5. [Medline].

  6. Donahue LA, Frank IN. Intravesical formalin for hemorrhagic cystitis: analysis of therapy. J Urol. Apr 1989;141(4):809-12. [Medline].

  7. Ehrlich RM, Freedman A, Goldsobel AB, Stiehm ER. The use of sodium 2-mercaptoethane sulfonate to prevent cyclophosphamide cystitis. J Urol. May 1984;131(5):960-2. [Medline].

  8. Haselberger MB, Schwinghammer TL. Efficacy of mesna for prevention of hemorrhagic cystitis after high-dose cyclophosphamide therapy. Ann Pharmacother. Sep 1995;29(9):918-21. [Medline].

  9. Iavazzo C, Athanasiou S, Pitsouni E, Falagas ME. Hyaluronic acid: an effective alternative treatment of interstitial cystitis, recurrent urinary tract infections, and hemorrhagic cystitis?. Eur Urol. Jun 2007;51(6):1534-40; discussion 1540-1. [Medline].

  10. Kanwar VS, Jenkins JJ, Mandrell BN, Furman WL. Aluminum toxicity following intravesical alum irrigation for hemorrhagic cystitis. Med Pediatr Oncol. Jul 1996;27(1):64-7. [Medline].

  11. Lee HJ, Pyo JW, Choi EH, et al. Isolation of adenovirus type 7 from the urine of children with acute hemorrhagic cystitis. Pediatr Infect Dis J. Jul 1996;15(7):633-4. [Medline].

  12. Levine LA, Richie JP. Urological complications of cyclophosphamide. J Urol. May 1989;141(5):1063-9. [Medline].

  13. Liu YK, Harty JI, Steinbock GS, et al. Treatment of radiation or cyclophosphamide induced hemorrhagic cystitis using conjugated estrogen. J Urol. Jul 1990;144(1):41-3. [Medline].

  14. McCarville MB, Hoffer FA, Gingrich JR, Jenkins JJ 3rd. Imaging findings of hemorrhagic cystitis in pediatric oncology patients. Pediatr Radiol. Mar 2000;30(3):131-8. [Medline].

  15. Miller LJ, Chandler SW, Ippoliti CM. Treatment of cyclophosphamide-induced hemorrhagic cystitis with prostaglandins. Ann Pharmacother. May 1994;28(5):590-4. [Medline].

  16. Raboni SM, Siqueira MM, Portes SR, Pasquini R. Comparison of PCR, enzyme immunoassay and conventional culture for adenovirus detection in bone marrow transplant patients with hemorrhagic cystitis. J Clin Virol. Aug 2003;27(3):270-5. [Medline].

  17. Rodriguez Luna JM, Teruel JL, Vallejo J, et al. Control of massive hematuria in idiopathic hemorrhagic cystitis after administration of conjugated estrogen. J Urol. Nov 1992;148(5):1524-5. [Medline].

  18. Russo P. Urologic emergencies in the cancer patient. Semin Oncol. Jun 2000;27(3):284-98. [Medline].

  19. Seber A, Shu XO, Defor T, et al. Risk factors for severe hemorrhagic cystitis following BMT. Bone Marrow Transplant. Jan 1999;23(1):35-40. [Medline].

  20. Tirindelli MC, Flammia G, Sergi F, Cerretti R, Cudillo L, Picardi A, et al. Fibrin glue for refractory hemorrhagic cystitis after unrelated marrow, cord blood, and haploidentical hematopoietic stem cell transplantation. Transfusion. Jan 2009;49(1):170-5. [Medline].

  21. Trigg ME, O'Reilly J, Rumelhart S, et al. Prostaglandin E1 bladder instillations to control severe hemorrhagic cystitis. J Urol. Jan 1990;143(1):92-4. [Medline].

  22. Vicente J, Rios G, Caffaratti J. Intravesical formalin for the treatment of massive hemorrhagic cystitis: retrospective review of 25 cases. Eur Urol. 1990;18(3):204-6. [Medline].

  23. West NJ. Prevention and treatment of hemorrhagic cystitis. Pharmacotherapy. Jul-Aug 1997;17(4):696-706. [Medline].

  24. Youn T, Trachtman H, Gauthier B. Clinical spectrum of gross hematuria in pediatric patients. Clin Pediatr (Phila). Mar 2006;45(2):135-41. [Medline].

Keywords

hemorrhagic cystitis, gross hematuria, HC, urinary frequency, urgency, dysuria, cyclophosphamide HC, cyclophosphamide hemorrhagic cystitis, viral-induced HC, viral-induced hemorrhagic cystitis, radiation-induced HC, radiation-induced hemorrhagic cystitis, bone marrow transplantation

Contributor Information and Disclosures

Author

Marcos Perez-Brayfield, MD, Consulting Staff, HIMA-San Pablo, San Juan, Puerto Rico
Marcos Perez-Brayfield, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, and American Urological Association
Disclosure: Nothing to disclose.

Coauthor(s)

Andrew J Kirsch, MD, FAAP, FACS, Clinical Professor of Urology, Emory University School of Medicine, Children's Healthcare of Atlanta; President, Georgia Urology, PA
Andrew J Kirsch, MD, FAAP, FACS is a member of the following medical societies: American Academy of Pediatrics, American Urological Association, and Society for Fetal Urology
Disclosure: QMED Grant/research funds Investigation, Consulting; COOK Urological Royalty Consulting

Medical Editor

Howard M Snyder III, MD, Professor, Department of Surgery, Division of Pediatric Urology, University of Pennsylvania School of Medicine
Howard M Snyder III, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Surgeons, American Medical Association, American Urological Association, and National Kidney Foundation
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner

Managing Editor

Harry P Koo, MD, Chairman of Urology Division and Director of Pediatric Urology, Virginia Commonwealth University; Professor of Surgery, VCU School of Medicine, Medical College of Virginia; Director of Urology, Children's Hospital of Richmond
Harry P Koo, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Surgeons, and American Urological Association
Disclosure: Nothing to disclose.

CME Editor

Paul D Petry, DO, FACOP, FAAP, Consulting Staff, Freeman Pediatric Care, Freeman Health System
Paul D Petry, DO, FACOP, FAAP is a member of the following medical societies: American Academy of Osteopathy, American Academy of Pediatrics, American College of Osteopathic Pediatricians, and American Osteopathic Association
Disclosure: Nothing to disclose.

Chief Editor

Marc Cendron, MD, Associate Professor of Surgery, Harvard School of Medicine; Consulting Staff, Department of Urological Surgery, Children's Hospital Boston
Marc Cendron, MD is a member of the following medical societies: American Academy of Pediatrics, American Urological Association, European Society for Paediatric Urology, Johns Hopkins Medical and Surgical Association, New Hampshire Medical Society, Society for Fetal Urology, and Society for Pediatric Urology
Disclosure: Nothing to disclose.

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