D i a g n o s i s an d

Management of Hematuria
Gabriella J. Avellino, MD, Sanchita Bose, MD, David S. Wang, MD*

KEYWORDS
 Hematuria  Trauma  Malignancy  Infection  Urolithiasis  Workup
 Clot retention  CBI

KEY POINTS
 Hematuria can be caused by a variety of etiologies, found along the entire genitourinary
tract, including urolithiasis, urinary tract infection, malignancy, iatrogenic causes and
trauma.
 The most important aspects of triaging and initial management of a patient with hematuria
are assessing hemodynamic stability, determining the underlying cause of hematuria, and
ensuring urinary tract drainage.
 Hematuria workup should be pursued in all patients presenting with hematuria in whom
benign causes of bleeding have been ruled out.

INTRODUCTION

Hematuria is a complex condition with a multitude of causes and treatments. It can be

a daunting situation when an otherwise nonurologic surgical patient has this condition.
This article provides an overview of the many aspects of this condition and provides
guidelines for treatment. In general, collaboration with the urology, and occasionally
nephrology, services is recommended in treating the general surgery patient with he-
maturia. After reading this article, the reader will gain knowledge on common etiol-
ogies, diagnosis, treatment, outcomes, and follow-up of the surgical patient with
hematuria to provide the best possible patient care.
Hematuria is commonly encountered in the inpatient setting where it accounts for
4% to 20% of inpatient urology consults and hospitalizations.1 Hematuria is the pres-
ence of blood cells in the urine. Gross hematuria is when blood is visible in the urine.
Microscopic hematuria is defined as 3 or more red blood cells per high-powered field
in a properly collected urine sample.
The initial evaluation of patients presenting with gross hematuria is 3-fold: assess
hemodynamic stability, determine the underlying cause of hematuria, and ensure uri-
nary drainage. The most important consideration in the initial evaluation of a patient

Disclosures: The authors have nothing to disclose.

Department of Urology, Boston Medical Center, Boston University School of Medicine,
725 Albany Street, Suite 3B, Boston, MA 02118, USA
* Corresponding author.
E-mail address: [email protected]

Surg Clin N Am 96 (2016) 503–515

http://dx.doi.org/10.1016/j.suc.2016.02.007 surgical.theclinics.com
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504 Avellino et al

with hematuria is hemodynamic stability with assessment of vital signs, physical ex-
amination, and hemoglobin/hematocrit, because an unstable patient must be treated
emergently. Examples of etiologies of hematuria that may cause emergent bleeding
include, but are not limited to, trauma such as intraperitoneal bladder rupture, ureter-
oarterial fistula, and hemorrhagic cystitis. By contrast, painless gross hematuria
without hemodynamic compromise is a condition that is generally worked up on an
outpatient basis. For this reason, it is extremely important to ensure that these patients
have outpatient urologic follow-up scheduled.
The best approach to treating a patient with hematuria is to identify the underlying
cause of hematuria, because the etiologies are diverse and often have very different
treatments. Common etiologies of hematuria in the surgical inpatient include urinary
tract infection (UTI), urolithiasis, malignancy, and trauma or iatrogenic causes (eg,
traumatic urethral catheter placement or anticoagulation).
There are several medications (such as phenazopyridine, nitrofurantoin, phenytoin,
and warfarin) that can cause or give the appearance of hematuria. Thus, inpatient
medications should be evaluated. Additionally, patients may be anticoagulated, which
may cause hematuria from a variety of sources such as benign prostatic hyperplasia
(BPH) or undiagnosed urinary tract malignancies.
Gross hematuria should always be considered significant, because it is a sign of
malignancy until proven otherwise. Roughly 4% of patients with microscopic hematu-
ria and up to 40% of patients with gross hematuria could be harboring a malignancy.2

RELEVANT ANATOMY AND PATHOPHYSIOLOGY

The etiology of hematuria can originate from anywhere along the urinary tract,
including the kidneys, ureters, bladder, prostate, and urethra (Table 1).

Kidney and Ureter

Specifically from the kidney, hematuria can be of glomerular origin, including medical
renal disease, and nonglomerular origin, which includes urologic disorders. Urologic
sources of hematuria from the kidney and ureter may include masses, both benign
and malignant, infection, urolithiasis, arteriovenous malformation, and trauma.
Kidney masses may represent metastasis or be primary renal tumors. Although
infrequent, the most common malignancies to metastasize to the kidneys include
lung, colorectal, head and neck, breast, and gastrointestinal tumors.3 Renal tumors
can be intraparenchymal or urothelial. Upper tract urothelial tumors can be found any-
where along the ureters and in the renal pelvis.

Table 1
Relevant anatomy and anatomic contributors to hematuria

Kidney/Ureter Bladder Prostate Urethra

 Glomerular  Uncomplicated cystitis  BPH  Urethritis
 Tumor  Radiation/hemorrhagic  Prostate cancer  Trauma
 Parenchymal cystitis  Prostatitis  Disruption
 Urothelial  Tumor  Traumatic Foley
 Infection  Trauma/rupture removal/placement
 Pyelonephritis  Urethral mass
 Calculi  Urethral caruncle
 Trauma  Urethral stricture
 Ureteraoarterial fistula

Abbreviation: BPH, benign prostatic hyperplasia.

 Diagnosis and Management of Hematuria 505

Infection of the kidney, or pyelonephritis, may cause microscopic or gross hematu-

ria. Pyelonephritis often results from ascending infection from the bladder (cystitis) and
can lead to high fevers and lateralizing flank pain. These symptoms can also be pre-
sent in patients with renal or ureteral calculi. Thus, if the suspicion is high (known his-
tory of nephrolithiasis, chronically bed bound patient, strong family history of kidney
stone formation), there should be a low threshold to image the patient with noncon-
trast computed tomography (CT).
Blunt, penetrating, or iatrogenic trauma can lead to hematuria from anywhere along
the urinary tract. The kidneys are the most frequently injured genitourinary organ, in up
to 5% of civilian traumas and 24% of traumatic abdominal solid organ injuries. The kid-
neys are especially at risk of deceleration injuries owing to their relatively fixed position
by the renal pelvis and vascular pedicles in the retroperitoneum.4 Accounting for only
1% of urologic injuries, ureteral injuries are infrequent. Iatrogenic ureteral injury during
gynecologic, urologic or colorectal surgeries accounts for 80% of ureteral injuries.5

Bladder
Bladder sources of hematuria include trauma, infection, hemorrhagic cystitis (from ra-
diation and/or chemotherapy exposure), and tumors. Bladder ruptures are catego-
rized as intraperitoneal, about 30% of the time, extraperitoneal 60%, and both in
the remaining 10%.6 Although more than 85% of blunt bladder injuries are associated
with pelvic fractures, less than 10% of blunt pelvic fracture patients are found to have
bladder injuries.5 They occur rarely in blunt abdominal trauma owing to the location of
the bladder in a relatively protected position in the pelvis. The typical site of intraper-
itoneal rupture is at the dome of the bladder, often in setting of a full bladder. Extrap-
eritoneal bladder ruptures often occur at the bladder neck or the base of the bladder.
Blood at meatus in the setting of trauma and pelvic fractures should make the clinician
suspicious of urethral or bladder injury.
Cystitis refers to any inflammation of the bladder, whether infectious or noninfec-
tious in origin. Infectious causes can be bacterial, viral, and fungal. Uropathogenic
Escherichia coli is the most common cause of UTIs. These bacteria have unique prop-
erties that allow them to bind to the outermost layer of the urothelium, enter the cells,
replicate, and eventually lead to cell lysis. Less common, viral cystitis is typically seen
in immunosuppressed patients owing to adenovirus and BK virus.
Noninfectious etiologies of cystitis include radiation and chemical cystitis, which
can lead to hemorrhagic cystitis. Radiation-induced cystitis can be seen at any time
after treatment, and there are no known risk factors for who will develop this compli-
cation. Radiation cystitis leads to damage of urothelium via apoptosis initiated by DNA
damage and can also affect the muscular layers of the bladder as well as the vascu-
lature. Chemical cystitis can be from various medications, for example, cyclophos-
phamide and/or ifosfamide chemotherapy. These medications are metabolized by
the liver, resulting in the formation of a harmful metabolite acrolein, which is filtered
into the urine, inducing urothelial damage.7
Bladder tumors are a common cause of gross and microscopic hematuria; approx-
imately 80% to 90% of patients with bladder cancer present with painless gross he-
maturia. Transitional cell carcinoma (or urothelial carcinoma) accounts for 90% of
bladder cancers and develops in the inner layer (urothelium) of the bladder. It is
described as a field change defect, meaning that it can affect the entire urothelium,
with significant potential for recurrence owing to highly malignant tumor biology.
The remaining 10% of bladder cancers include but are not limited to squamous cell,
adenocarcinoma, and small cell. Risk factors for developing bladder cancer are out-
lined in Box 1.
506 Avellino et al

Box 1
Risk factors for urologic malignancy

 Smoking history
 Advanced age
 Male gender
 History of pelvic irradiation or certain chemotherapeutics (eg, cyclophosphamide)
 Chronic bladder inflammation (indwelling catheter, chronic urinary tract infections)
 Occupational exposures (eg, aromatic amines, aniline dyes, benzene)

Prostate
Prostatic causes of hematuria can largely be attributed to prostatic hyperplasia. The
prostatic hyperplastic process is owing to an imbalance between cell death and cell
proliferation, which eventually leads to cell accumulation.8 In this process, there is
also expression of vascular endothelial growth factor, which makes the prostate an
extremely vascular organ prone to bleeding. Prostatic malignancy and infection of
the prostate, or prostatitis, are other contributors to hematuria of prostatic source.
Bacterial prostatitis is the result of focal uropathogenic bacteria residing in the pros-
tate gland. The most common cause of bacterial prostatitis, both acute and chronic,
is the Enterobacteriaceae family of Gram-negative bacteria.9 Locally advanced pros-
tate cancer may also cause hematuria.
Urethra
Urethral causes of hematuria include infection (urethritis), urethral masses, and
trauma. Urethritis is inflammation of the urethra, and is usually infectious in origin.
As with any infection, a urinalysis and culture as well as testing for Neisseria gonorrhea
and chlamydia are useful. An uncommon cause of emergent urethral bleeding is in the
setting of traumatic Foley catheter manipulation or removal (eg, by a demented or
delirious patient or during transfers). After traumatic catheter removal, reinsertion of
the catheter is recommended.1 If resistance is met on reinsertion, there should be
further evaluation of urethral integrity, either with bedside cystoscopy or retrograde
urethrogram.

CLINICAL PRESENTATION AND EXAMINATION

Patients with gross hematuria have a wide range of presentations (Table 2). As
mentioned, the first and most important part of evaluation of a patient with hematuria
is hemodynamic stability. Patients with hypotension, tachycardia, and low hemoglo-
bin/hematocrit may require emergent intervention. This can involve surgical interven-
tion (ie, fulguration of prostatic bleeding, angioembolization by interventional
radiology) as well as resuscitation.
Obtaining a thorough history is essential in evaluating patients with hematuria
because the history often provides clues for diagnosis of underlying etiology (eg, a
strong family history of prostate cancer or a long history of smoking provides further
evidence of likely urologic malignancy). Although patients with hematuria may be
asymptomatic, common presenting symptoms include dysuria, urinary frequency
and/or urgency, and abdominal and/or flank pain.
In the physical examination of the patient with hematuria, it is important to perform a
focused examination of the abdomen, flanks, pelvic examination in women, digital
 Diagnosis and Management of Hematuria 507

Table 2
Clinical presentations by etiology

Urinary Tract Hemorrhagic

Infection Urolithiasis Malignancy Prostate Cystitis Trauma
 Dysuria  Symptoms of  Often  Enlarged  Persistent  Hematuria
 Hematuria urinary tract painless prostate on bleeding  Blood at
 Frequency/ infection  Irritative digital rectal from meatus
urgency  Lateralizing voiding examination bladder  Clinical
 Incontinence flank pain symptoms  Clot  Urgency correlation
 Small  Fevers (frequency, retention  Frequency  Inability to
volume voids urgency,  Range of  Bladder pain void
 Foul- dysuria) symptoms
smelling, (frequency,
cloudy urine urgency,
 Suprapubic decreased
pain stream,
nocturia)

rectal examination in men, and external genitourinary examination. Pain on digital

rectal examination can clue the clinician into a diagnosis of prostatitis, and a nodule
on digital rectal examination raises the concern for prostatic malignancy. Flank or
costovertebral angle tenderness may signal a diagnosis of pyelonephritis or urolithia-
sis. Pain from obstructing ureteral calculi can often radiate to the lower abdomen or
scrotum.
In addition to a focused physical examination, as discussed, the urine must also be
examined. The color and viscosity of the urine often provides valuable clinical informa-
tion. As with bleeding in other areas of the body, dark red/brown urine often signifies
the presence of old blood, whereas bright red blood likely signifies active, new
bleeding. Increased viscosity of urine as well as the presence of clots in voided urine
is concerning because this may signal that a patient may develop clot retention. Clot
retention is defined as blood clots within the bladder that obstruct the flow of urine
causing symptomatic urinary retention.

Urinary Tract Infection

UTIs can occur in any part of the genitourinary tract (cystitis, urethritis, prostatitis,
pyelonephritis, epididymitis). Although patients with a UTI can be asymptomatic, com-
mon symptoms associated with cystitis include dysuria, hematuria, urinary frequency
and/or urgency, incontinence of urine, small volume voids, foul-smelling urine, and
suprapubic pain. An indurated and tender epididymis in addition to the above symp-
toms is an easily localizable feature of epididymitis. Symptoms associated with upper
UTIs, namely pyelonephritis, include these symptoms with the addition of fevers,
rigors, flank pain, nausea, and vomiting. Although symptoms are very helpful in the
diagnosis of UTI, they do not accurately localize the infection within the genitourinary
tract.10 UTI in the setting of obstructive uropathy or stones is a urologic emergency.
Patients with urolithiasis often present with dysuria and hematuria along with
intense lateralizing flank pain. When the suspicion is high, CT abdomen/pelvis without
contrast in the prone position is the modality that often diagnoses ureteral and renal
stones. It is important to understand the indications for urgent intervention (ie, place-
ment of ureteral stent or nephrostomy tube) for obstructing stones, which include fe-
ver, uncontrollable pain despite treatment with narcotics, solitary kidney, renal
dysfunction, bilateral ureteral stones, and hemodynamic instability.
508 Avellino et al

Urologic Malignancy
Patients with occult urologic malignancy often present with painless gross hematuria,
which may be the only abnormality on presentation. Irritative voiding symptoms
(frequency, urgency, dysuria) can also be symptoms of malignancy, particularly carci-
noma in situ of the bladder. Roughly 80% of patients with bladder carcinoma in situ
present with irritative voiding symptoms, and the presence of these symptoms dou-
bles the risk of harboring carcinoma in situ in patients with hematuria (from 5% to
10%).11 However, the symptom combination of hematuria and voiding dysfunction
is quite common in a variety of urologic pathology including UTI, prostatic hypertro-
phy, and urolithiasis, which makes diagnosis quite complex.
Hemorrhagic Cystitis
A particularly difficult to manage etiology of gross hematuria is hemorrhagic cystitis.
This condition is characterized by diffuse, persistent bleeding from the bladder mucosa.
The severity of bleeding can range from mild bleeding managed conservatively to life-
threatening bleeding requiring blood transfusion, bladder irrigation, and/or operative
intervention. Hemorrhagic cystitis can be associated with irritative symptoms, including
urinary urgency, frequency, and bladder pain.12 Typically hemorrhagic cystitis is only
seen in patients with known risk factors, such as prior pelvic radiation and cyclophos-
phamide chemotherapy. Reports indicate that up to 5% of patients who receive pelvic
radiation will experience moderate or severe persistent gross hematuria.13
Trauma
Trauma patients often present with multiple injuries and hematuria as a result of urinary
tract injury. Although patients with renal and bladder injuries often present with gross
hematuria, a patient with urethral disruption/injury may present with inability to void
and blood at urethral meatus. In ureteral trauma, gross hematuria is unfortunately
not a reliable indicator of injury, and these injuries are often diagnosed in a delayed
fashion. Suspicion for ureteral injury should arise in patients with bowel, bladder, or
retroperitoneal injuries or in patients with high velocity pelvic or vertebral fractures.14
Prostatic Enlargement
Prostatic enlargement may cause hematuria in men in a variety of scenarios, including
BPH, prostatitis, and advanced prostate cancer. The prostate can bleed owing to a
variety of aggravators (including Foley catheterization, infection, and anticoagulation).
Localization of hematuria to the prostate should be determined after a complete eval-
uation of the hematuria is completed; other etiologies for the hematuria must be
excluded.1 Hematuria from prostatic enlargement has a range of presentations from
mild bleeding to recalcitrant bleeding with clots and thus has a variety of treatments.
Ureteroarterial Fistula
Ureteroarterial fistula is an infrequent but very serious cause of gross hematuria. It can
be life threatening. This diagnosis requires a high degree of suspicion. Patients may
present with gross hematuria, symptomatic anemia, and lateralizing flank pain. Risk
factors include chronic indwelling stents, previous pelvic radiation, pelvic or vascular
surgery, and vascular disease.15

DIAGNOSTIC PROCEDURES AND DIAGNOSIS

After excluding benign causes, the presence of hematuria should precipitate a uro-
logic evaluation. The workup for hematuria includes history, examination, laboratory
 Diagnosis and Management of Hematuria 509

studies, cystoscopy, and upper tract imaging (with CT urogram, which is the standard,
or MR urogram vs renal ultrasound with retrograde pyelography for patients with renal
dysfunction; Table 3). The initial step in diagnosis is to obtain a properly collected,
midstream clean catch urinary specimen and identify 3 or more red blood cells per
high-power field. A dipstick test is not adequate to identify microhematuria because
it can result positive in the setting of oxidation or myoglobinuria. This must be
confirmed by a microscopic urinalysis. This analysis will also allow the identification
of red blood cell casts, proteins, and dysmorphic red blood cells, which can indicate
a medical renal source for hematuria. A urine culture should also be sent to assess for
infection. If the workup is unremarkable but microscopic hematuria persists, a urologic
evaluation can be repeated in 3 to 5 years.
In the history, in addition to assessing risk factors for urologic malignancy, the pro-
vider should inquire about medical renal disease, UTI, trauma, and menstruation.
Physical examination should include a thorough abdominal and genital examination
and blood pressure reading.
Laboratory tests should include the estimated glomerular filtration rate, creatinine,
and blood urea nitrogen to evaluate renal function. Renal function can determine eligi-
bility for further diagnostic testing. Although once considered a mandatory part of the
workup, urine cytology has limited use and should not be part of the initial workup for
asymptomatic microscopic hematuria.16
Cystoscopy, which involves direct visualization of the urethra and bladder by cam-
era, should be performed for all patients older than 35 years of age. Cystoscopy
should be done at the discretion of the physician for any patients younger than
35 years, such as if there is concern for malignancy owing to exposures or irritative
voiding symptoms. This can be done in the office setting for the appropriately selected
patient. Cystoscopy allows identification of urethral lesions, strictures, and false pas-
sages, bladder lesions or masses, and lateralizing hematuria from a ureteral orifice.
Additionally, retrograde radiographic studies can be done if fluoroscopy is available.
The gold standard for imaging in hematuria workup is multi-phasic CT urography.
This includes 3 phases with and without contrast: a noncontrast phase for identifica-
tion of stones, a nephrogenic phase for evaluation of renal masses, and an excretory
phase for assessment of filling defects in the collecting system (ureters and bladder).
Another option is MR urography. If CT or MRI are unavailable or patient is ineligible
owing to pregnancy, iodinated contrast allergy, or renal insufficiency, renal and
bladder ultrasound examination with retrograde pyelogram is an option.
In settings of traumatic hematuria, if stable enough for imaging, the patient should
undergo intravenous contrast-enhanced CT of the abdomen and pelvis with delayed
images to evaluate the collecting system. If the patient is too unstable and proceeds
directly to operating room without imaging, an intravenous pyelogram can be obtained
and should be performed if nephrectomy is being considered to confirm presence of
contralateral kidney.

Table 3
Hematuria workup

Cystoscopy Urine Cytology Upper Tract Imaging

 Evaluates urethral  Examines urine for cancer cells  CT urogram gold standard
and bladder  Not recommended in  Renal ultrasound with
mucosa for masses asymptomatic microhematuria retrograde pyelogram vs
 Consider in high-risk patients MR urogram in renal
insufficiency
510 Avellino et al

If bladder rupture is suspected, a CT or plain film cystogram can elucidate extrav-

asation. A cystogram involves images captured after filling the bladder and then after
emptying to identify any extravasated contrast concealed by the distended bladder.5
Contrast outlining bowel supports an intraperitoneal rupture. Contrast localized in the
pelvis supports an extraperitoneal rupture. If there is concern of urethral injury, a retro-
grade urethrogram should be done before Foley catheter placement and will show
extravasation of contrast outside the urethra.
If the source of hematuria has not yet been clarified by imaging methods already
mentioned or if the patient is hemodynamically unstable, percutaneous angioemboli-
zation can be diagnostic and therapeutic as an alternative to surgical exploration.5

INTERVENTIONS AND TREATMENT

Management and treatment can vary depending on the etiology of hematuria.

Urinary Tract Infections

Infections of the urinary tract (pyelonephritis, cystitis, prostatitis, epididymitis, and ure-
thritis) are common and treatable causes of hematuria. In terms of management of these
patients, all patients should have urine culture performed before initiation of antibiotics.
Antibiotic selection should focus on coverage of uropathogens (Gram-negative and
Gram-positive bacteria). Antibiotic coverage should be broad when initiated, and even-
tually narrowed based on culture data. A hospital’s antibiograms should be used in anti-
biotic selection. Consider consultation with the infectious disease service in patients
with complex infections to further aid in antibiotic selection and duration of therapy.

Urolithiasis
With kidney stone disease affecting 1 in 11 people in the United States, it is a very
common and important entity for clinicians to learn to diagnose and manage.17 Unlike
cholelithiasis, appendicitis, and other surgical conditions, surgical treatment of stones
is not the endpoint in stone therapy, because patients have a high incidence of recur-
rence of disease. In terms of stone management, it is important to recognize which pa-
tients can be managed non-operatively with medical expulsive therapy and which
patients will require urgent surgical intervention with ureteral stenting or percutaneous
nephrostomy tube placement.
There are several indications for the urgent surgical management of ureteral stones.
These indications include intractable pain, solitary kidney, bilateral ureteral stones with
obstruction, high-grade unilateral obstruction, renal dysfunction, abnormal ureteral
anatomy, infection (which can manifest with fever, sepsis, and positive urinalysis
and urine culture), hemodynamic compromise, and stones that are unlikely to pass
spontaneously.18
If the patient is hemodynamically compromised or septic, it is prudent to proceed
with percutaneous nephrostomy decompression, because this procedure requires
less manipulation of the urinary tract. Although the general surgery patient may
have nonurologic causes for being hemodynamically compromised, a concurrent
obstructing stone must be addressed.
Medical expulsive therapy is a non-invasive and viable approach to managing the
patient with uncomplicated urolithiasis (ie, in the absence of factors requiring urgent
intervention). The ideal candidate for medical expulsive therapy is a patient with a
stone but without signs of hemodynamic compromise, infection, or obstruction. It
should be noted that the size and location of the ureteral stone are extremely impor-
tant. The rate of spontaneous passage is much greater for distal ureteral stones (71%)
 Diagnosis and Management of Hematuria 511

than for proximal ureteral stones (22%).19 Medical expulsive therapy includes high-
rate intravenous fluids, adequate pain control with narcotics, and alpha-1 antagonist
therapy, most commonly tamsulosin, although there is a debate in current literature
on the utility of tamsulosin.20
Urologic Malignancy
Gross hematuria should always be taken seriously as a “red flag” for urologic malig-
nancy. Should painless gross hematuria be present in the general surgery patient in
the absence of other etiologies of hematuria (trauma, infection, urolithiasis, etc), urologic
malignancy should be high on the differential. In addition to referral to urology, the gen-
eral surgeon can begin the process of working up gross hematuria by ordering labora-
tory and imaging studies. Urology completes the evaluation with cystoscopy, as an
outpatient in the majority of cases, to rule out urethral and bladder mucosal pathology.
Clot Retention
The initial management of hematuria is resuscitation and bladder drainage. It is also
important to identify risk factors and reversible causes for severe hematuria. In terms
of catheter selection, large-bore catheters are preferable to ease passage of clots. Uri-
nary catheters are sized in the French system, where 1 French equals 0.33 cm in
circumference (not luminal diameter). In patients with severe hematuria and passage
of clots, the best catheters to choose are large bore (22 French) with 3 channels to
allow for the possibility of manual and continuous bladder irrigation (CBI).1 After the
catheter is in place, manual irrigation with normal saline using catheter-tipped syringes
should be performed to clear any clots from the bladder. Should the urine clear after
adequate manual irrigation, the focus should be on conservative management with hy-
dration and resuscitation. Should severe hematuria and clots persist despite adequate
manual irrigation, then CBI may be used. In CBI, irrigation fluid continuously flows into
a patient’s bladder via a third port on the 3-way urethral catheter and is drained out via
the exit port. Although CBI is an excellent treatment for severe hematuria, patients
must be monitored for catheter obstruction during CBI, which raises the risk of bladder
perforation. If bleeding persists despite this treatment, the clinician should consider
intravesical therapy, cystoscopy with fulguration, or embolization (Box 2).

Box 2
Clot Retention

Assess hemodynamic stability/resuscitate

Identify etiology
Place large catheter (22 French), manually irrigate
Urine clears
Hydration
Resuscitation
Hematuria workup
Urine does not clear
Imaging to evaluate clot burden
Start continuous bladder irrigation
Assess for reversible causes of hematuria (such as anticoagulation status)
Consider operative intervention or intravesical therapy
512 Avellino et al

Prostatic Hematuria
Prostate-related gross hematuria can be due to prostatitis, BPH, or advanced prostate
cancer. The initial management of these patients is the same as with any patient with
severe hematuria (bladder drainage, resuscitation, treatment of reversible causes).
In patients with acute prostatic bleeding owing to BPH, use of 5-alpha reductase in-
hibitor (finasteride) should be considered. Finasteride is associated with decreased
prostatic blood flow by inhibition of vascular endothelial growth factor expression.21
Finasteride is dosed 5 mg once daily and is associated with sexual side effects
(decreased libido and trouble with erections and ejaculation).
Patients with advanced prostate cancer may also present with hematuria. If stable,
the patient may be considered for surgical treatment (limited transurethral resection of
prostate), radiation therapy, or androgen deprivation for control of hematuria.
Androgen deprivation decreases prostate tissue vascularity and can control refractory
bleeding from the prostate.1 Should hematuria from BPH or prostate cancer persist
despite conservative therapies, operative intervention should be considered (cystos-
copy with fulguration and clot evacuation, embolization).

Hemorrhagic Cystitis
Hemorrhagic cystitis presents with severe hematuria due to diffuse bladder mucosal
bleeding. The patient may even present with clot retention. Often the patient endorses
a history of passing significant clot burden and has known risk factors (ie, history of
pelvic radiation, cyclophosphamide chemotherapy). If a patient is scheduled to
receive cyclophosphamide, the administration of 2-mercaptoethane sulfonate sodium
(Mesna) can be bladder protective by neutralizing the harmful metabolite acrolein.
These patients should also undergo a full hematuria workup to rule out other causes
of hematuria, namely active urologic malignancy. The acute management of these pa-
tients remains the same as discussed. There are additional treatments that can be
used for these patients such as intravesical agents (alum, aminocaproic acid, etc),
fulguration with electrocautery, and hyperbaric oxygen. If still unable to control, urinary
diversion (cystectomy, bilateral percutaneous nephrostomy) is an option.

Urotrauma
Traumatic injury to the urinary tract often results in gross hematuria. Patients with uri-
nary tract trauma frequently present in the setting of multiple organ injuries. Trauma is
the cause of 150,000 deaths per year in the United States and is the leading cause of
death in adults under 45 years of age.22 Treatment of urinary tract trauma is complex
and is based on the organ that is injured. Intraperitoneal bladder rupture usually re-
quires operative management, whereas extraperitoneal rupture can be managed non-
operatively with catheterization. Urethral injury may be managed with Foley catheter
alone or may require urinary diversion, repair, or ureteral stenting. Urethral injury
may require diversion with suprapubic tube and delayed repair.
Traumatic urethral catheterization and removal can also cause hematuria. Urethral
catheter trauma may be remedied simply with replacement or manipulation of the
catheter; however, about 30% may require prolonged catheterization, CBI, cystos-
copy, or suprapubic tube placement. Urethral catheter placement can cause trau-
matic hematuria, especially in men with BPH or on anticoagulation.

Ureteroarterial Fistulae
Although it is an uncommon cause of hematuria, ureteroarterial fistula is a life-
threatening condition. The general surgeon should have a high degree of suspicion
 Diagnosis and Management of Hematuria 513

Box 3
Hematuria: pearls and pitfalls

 To limit urethral catheter trauma in men, inflate the Foley catheter balloon only if:
 Catheter is completely hubbed at urethral meatus at junction with the balloon port.
 There is return of urine.
 Make sure the patient’s catheter is not obstructed while he or she is on continuous bladder
irrigation, particularly if complaining of abdominal pain.
 A large-bore catheter (22 French) should be used for bladder lavage/continuous bladder
irrigation
 All patients with gross hematuria warrant a hematuria workup.
 Obtain urinalysis and urine culture on all patients with hematuria.

of this condition in patients presenting with hematuria, lateralizing flank pain, down-
trending blood counts, and risk factors (chronic indwelling ureteral stents, history of
pelvic irradiation or pelvic and/or vascular surgery). Immediate involvement of vascular
surgery or endovascular treatment by interventional radiology is essential.

SUMMARY

Hematuria in the general surgery patient is a unique and complex situation that warrants
close investigation. After careful evaluation of history and physical examination, labora-
tory tests, and indicated imaging, the source may remain elusive. In a study screening
patients with hematuria on initial microscopic urinalysis, 2% were found to have bladder
cancer, 22% infection, 10% BPH, and 65% remained of unknown cause.23
The general surgeon should take into consideration the circumstances under which
new-onset gross hematuria develops. For example, if in the postoperative period,
consider the operation, anticoagulation status, and whether the patient had a urethral
catheter placed. Iatrogenic hematuria can be owing to unidentified intraoperative
complications, such as laceration or thermal injury to ureter or bladder, or inflation
of urethral catheter balloon in urethra.24 Certain medications can alter the urine color
to give the appearance of hematuria; thus, the medication list should be reviewed.
Gross hematuria can occasionally lead to a symptomatic reduction in hematocrit
requiring transfusion, which can occur in cases related to trauma, ureteroarterial fis-
tula, and hemorrhagic cystitis. Thus, these etiologies should be dealt with emergently.
In this article, we have outlined some of the most common causes of hematuria that
a general surgeon may encounter, such as UTIs, urolithiasis, urologic malignancy, uri-
nary tract arterial fistulae, prostatic bleeding, hemorrhagic cystitis, and trauma, as well
as the clinical scenario of clot retention. Pearls and pitfalls of addressing hematuria are
provided to the reader in Box 3. We hope that reading this article provides the general
surgeon with an armamentarium of knowledge to properly triage and initiate diagnosis
and treatment of the complex general surgery patient with hematuria.

REFERENCES

1. Linder BJ, Boorjian SA. Management of emergency bleeding, recalcitrant clots

and hemorrhagic cystitis. AUA Update Series. Maryland: American Urological
Association Education and Research, Inc; 2015; 34 (lesson 3).
2. Grossfeld GD, Litwin MS, Wolf JS Jr, et al. Evaluation of asymptomatic microscopic
hematuria in adults: an American Urologic Association best practice policy – part I:
definition, detection, prevalence, and etiology. Urology 2001;57(4):599–603.
514 Avellino et al

3. Zhou C, Urbauer DL, Fellman BM, et al. Metastases to the kidney: a comprehen-
sive analysis of 151 patients from a tertiary referral centre. BJU Int 2015 [Epub
ahead of print] Available at: www.bjui.org.
4. Morey AF, Brandes S, Dugi DD, et al. Urotrauma: AUA guideline. J Urol 2014;
192(2):327–35.
5. Gross JA, Lehnert BE, Linnau KF, et al. Imaging of urinary system trauma. Radiol
Clin North Am 2015;53(4):773–88.
6. Morey AF, Iverson AJ, Swan A, et al. Bladder rupture after blunt trauma: guide-
lines for diagnostic imaging. J Trauma 2001;51:683.
7. Haldar S, Dru C, Bhowmick NA. Mechanisms of hemorrhagic cystitis. Am J Clin
Exp Urol 2014;2(3):199–208.
8. Roehrborn C. Chapter 91: Benign prostatic hyperplasia. In: Wein AJ,
Kavoussi LR, Novick AC, et al, editors. Campbell-Walsh urology. 10th edition.
Philadelphia: Saunders; 2011. p. 2570–610.
9. Nickel J. Chapter 11: Prostatitis and related conditions, orchitis and epididymitis.
In: Wein AJ, Kavoussi LR, Novick AC, et al, editors. Campbell-Walsh urology. 10th
edition. Philadelphia: Saunders; 2011. p. 327–56.
10. Nguyn H. Chapter 13. Bacterial infections of the urinary tract. In: Tanagho EA,
McAninch JW, editors. Smith’s General Urology. 16th edition. New York:
McGraw-Hill Companies Inc; 2004. p. 203–27.
11. Zincke H, Utz DC, Farrow GM. Review of Mayo Clinic experience with carcinoma
in situ. Urology 1985;26(4 Suppl):39–46.
12. Liem X, Saad F, Delouya G. A practical approach to the management of radiation-
induced hemorrhagic cystitis. Drugs 2015;75(13):1471–82.
13. Linder BJ, Tarrell RF, Boorjian SA. Cystectomy for Refractory Hemorrhagic
Cystitis: Contemporary Etiology, Presentation and Outcomes. The Journal of Urol-
ogy 2014;192(6):1687–92.
14. Elliott SP, McAninch JW. Ureteral injuries from external violence: the 25-year
experience at San Francisco General Hospital. J Urol 2003;170:1213.
15. Krambeck AE, DiMarco DS, Gettman MT, et al. Ureteroiliac artery fistula: diag-
nosis and treatment algorithm. Urology 2005;66(5):990–4.
16. Cargan J, Kavoussi LR. Chapter 3: Lack of utility of routine urine cytology as part
of hematuria workups. In: Wein AJ, Kavoussi LR, Novick AC, et al, editors. Camp-
bell-Walsh urology. 10th edition. Philadelphia: Saunders; 2014.
17. Pearle MS, Goldfarb DS, Assimos DG, et al. Medical management of kidney stones:
AUA guideline, American Urological Association; 2014. Maryland: American
Urological Association Education and Research Inc. Available at: https://www.
auanet.org/education/guidelines/management-kidney-stones.cfm. Accessed
August 30, 2015.
18. Matlaga BR, Lingeman JE. Chapter 48: Surgical management of upper urinary
tract calculi. In: Wein AJ, Kavoussi LR, Novick AC, et al, editors. Campbell-Walsh
urology. 10th edition. Philadelphia: Saunders; 2011. p. 1357–410.
19. Morse RM, Resnick MI. Ureteral calculi: natural history and treatment in an era of
advanced technology. J Urol 1991;145:263–5.
20. Pickard R, Starr K, MacLennan G, et al. Medical expulsive therapy in adults with
ureteric colic: a multicentre, randomised, placebo-controlled trial. Lancet 2015;
386:341–9.
21. Rastinehad AR, Ost MC, VanderBrink BA, et al. Persistent prostatic hematuria.
Nat Clin Pract Urol 2008;5:159.
 Diagnosis and Management of Hematuria 515

22. Centers for disease control and prevention: injury prevention & control: data &
statistics (WISQARSTM). Available at: http://www.cdc.gov/injury/wisqars/
LeadingCauses.html. Accessed September 27, 2015.
23. Elias K, Svatek RS, Gupta S, et al. High risk patients with hematuria are not eval-
uated according to guideline recommendations. Cancer 2010;116(12):2954–9.
24. Leuck AM, Wright D, Ellingson L, et al. Complications of Foley catheters—is infec-
tion the greatest risk? J Urol 2012;187(5):1662–6.