Hematuria - evaluation and management

EVALUATION AND
MANAGEMENT OF HEMATURIA
Dept of Urology
Govt Royapettah Hospital and Kilpauk Medical College
Chennai

Moderators:
Professors:
• Prof. Dr. G. Sivasankar, M.S., M.Ch.,
• Prof. Dr. A. Senthilvel, M.S., M.Ch.,
Asst Professors:
• Dr. J. Sivabalan, M.S., M.Ch.,
• Dr. R. Bhargavi, M.S., M.Ch.,
• Dr. S. Raju, M.S., M.Ch.,
• Dr. K. Muthurathinam, M.S., M.Ch.,
• Dr. D. Tamilselvan, M.S., M.Ch.,
• Dr. K. Senthilkumar, M.S., M.Ch.
Dept of Urology, GRH and KMC, Chennai. 2

CLASSIFICATION
According to its visibility and timing during the
urinary stream
Gross/ Frank
• Initial
• Terminal
• Total
Microscopic
• Asymptomatic
• Symptomatic
3
Dept of Urology, GRH and KMC, Chennai.

CLASSIFICATION
According to origin
•Urinary bladder
•Prostate
•Urethra
•Upper urinary tract
4

TIMING OF HEMATURIA
Gives indication of the source of hematuria,
Initial
• Urethral source Total
• Bladder or
above
Terminal
• Bladder trigone
• Bladder neck
• Prostate
5

TIMING OF HEMATURIA
Initial
• Urethral source
Total
• Bladder or
above
Terminal
• Bladder trigone
• Bladder neck
• Prostate
6

DIFFERENTIAL DIAGNOSIS
Pigmenturia
endogenous
sources
e.g., bilirubin,
myoglobin,
porphyrins
foods ingested
e.g., beets and
rhubarb
drugs taken
e.g.,
phenazopyridine
dehydration
7

Pigmenturia
• Cause false-positive chemical tests (e.g., urine
dipstick)
• This distinction can be made easily by
urinalysis with microscopy.
8

Vaginal bleeding in women
• obtaining a careful menstrual history
• collecting the specimen when the patient is
not having menstrual or gynecologic bleeding,
• if necessary, obtaining a catheterized
specimen
9

MICROSCOPIC HEMATURIA
• Sign rather than a symptom
• Laboratory diagnosis
• Definition
– Presence of RBCs on microscopic examination of
the urine not evident on visual inspection of the
urine.
• The prevalence of MH among healthy
participants in screening studies is
approximately 6.5%
10

MICROSCOPIC HEMATURIA
• Higher rates noted in
– Males
– older patients
– smokers
• Categorized by the presence or absence of
associated symptoms
• Quantified according to number of RBCs per
high-power field (HPF)
11

Criteria for the Diagnosis
normal processes
(e.g., sexual
activity, exercise)
significant medical
conditions
(GU malignancy)
12

• Differences in thresholds for initiating an
evaluation reflect efforts to balance the
• Importantly, none have been robustly validated.
Benefits
Cost
analysis
Harms
13

Criteria
3 or more
AUA- Single UA
Canada, Dutch- 2 out
of 3 UA
Japan- 5 or more RBCs/
HPF on a single UA
Kaiser permanente-
More than 3 RBCs/HPF
on 2 out of 3 UAs
NICE- 1+ blood or more
on urine dip stick test
PLUS Dysuria or
elevated leukocytosis
14

URINE MICROSCOPY
Specimen collection
Centrifuge
Pipette, slide
Microscopy
15

URINE MICROSCOPY
16

DIPSTICK TEST
Dipsticks frequently demonstrate both colored dots and field color change
The degree of color change is directly related to the amount of hemoglobin present
which changes color according to the degree and amount of oxidation.
catalyzes the reaction and causes subsequent oxidation of a chromogen indicator
Haemoglobin in contact with an organic peroxidase substrate
17

DIPSTICK TEST
• Free hemoglobin and myoglobin in the urine
• Absorbed into the reagent pad
• Catalyze the reaction within the test paper
• Produce a field change effect in color.
18

DIPSTICK TEST
coalescence of the dots occurs when there are more than 250 erythrocytes/mL
The greater the number of intact erythrocytes-greater the number of dots that will appear on the test paper
localized free hemoglobin on the pad produces a corresponding dot of color change.
undergo hemolysis
come in contact with the reagent test pad
Intact erythrocytes in the urine
19

Requirement for Microscopic Evaluation
Urine dipstick for
blood
Haemoglobin,
myoglobin
Urine microscopy
3 or more
RBCs/HPF
Further Evaluation
Detects peroxidase
activity using
benzidine
20

Requirement for Microscopic Evaluation
False
positive
False
Negative
dilute urine
(osmolality
<308 mOsm)
Vigorous physical
or sexual activity
prolonged
recumbency
(first void in
morning)
21

Selecting Patients for Evaluation
Vigorous exercise
• considered a diagnosis of exclusion.
• Thus it is necessary to confirm the absence of
MH after a period of abstinence from exercise
22

Hematuria and anticoagulants
• e.g., warfarin, enoxaparin, heparin, aspirin,
clopidogrel, apixiban, dabigatran
• Should undergo a complete evaluation in the
same manner as patients not taking such
medications
23

• Prevalence of hematuria, as well as the likelihood
of finding genitourinary cancers
– no different from patients not taking such medications
• May unmask genitourinary lesions at an earlier
stage
• Patients taking antithrombotic agents were more
than twice as likely to be diagnosed with bladder
cancer within 6 months after an episode of
hematuria
24

25

26

• ACOG, AUGS- 2017: Withold evaluation in
women if
– asymptomatic microscopic hematuria
– never-smoked
– 35 to 50 years
– fewer than 25 RBCs/ HPF
• the risk of urinary tract malignancy in such
patients has been demonstrated to be less
than or equal to 0.5%
27

Screening: Hematuria and Bladder Cancer
• Mass screening for bladder cancer
– harms and costs outweigh the potential benefits
• Opportunistic screening events
– many primary care providers perform urinalysis as
part of routine health examinations
28

+AMH
(≥3 RBCs/HPF on UA with
microscopy)
History and physical assessment
for other potential AMH causes
(e.g., infection, menstruation,
recent urologic procedures)
Repeat UA after treatment of
other cause(s).
Release from care
Follow Protocol of history and
Physical assessment: Negative
Renal function testing
Cystoscopy
Imaging (CTU)
Follow up with at least one
UA/micro yearly for at least 2
years.
Follow persistent MH with annual
UA. Consider nephrologic
evaluation. Repeat anatomic
evaluation within 3 to 5 years* or
sooner, if clinically indicated.
Release from care
Treatment and Follow up as
indicated by diagnosis. Reevaluate
for MH after resolution of
identified condition
Concurrent nephrologic workup if
proteinuria, red cell morphology,
or other signs indicate
nephrologic causes
+
+
+
+
-
-
-
-
29

HISTORY
Goal should be to identify causes that would warrant
variation from the standard evaluation, such as
• Infection
• Menstruation
• Recent vigorous exercise
• Known medical renal disease
• Acute viral illness
• Trauma
• Presence of foreign bodies in the urinary tract
• Recent urologic instrumentation
30

HISTORY
• Associated symptoms-
– GH, voiding symptoms, or flank pain.
• Urologic history
– any surgeries or febrile UTIs.
• General medical history
– to identify potentially contributory diagnoses
– hypertension, renal insufficiency, bleeding
disorders, or sickle cell disease.
31

HISTORY
• Current medication use, including
– anticoagulants and antiplatelet therapies
– recent coagulation values
– any concomitant medications that would potentiate
the effects of blood thinners.
• Family history
– nephritis, polycystic kidneys, and rare familial tumor
syndromes of the kidney (e.g., von Hippel-Lindau
syndrome) or urothelium (e.g., Lynch syndrome) also
may be informative
• Tobacco use
32

PHYSICAL EXAMINATION
• Focus on the genitourinary system
– flank tenderness
– masses in the flank, abdomen, suprapubic area, or
urethra;
– enlarged, nodular, tender, or fluctuant prostate
33

PHYSICAL EXAMINATION
• Signs of coagulopathy (bruising)
• infection (fever)
• renal disease (hypertension, edema).
• If urethral stricture or BPH is suspected, a UFR
and PVR measurement may be helpful as well.
34

+AMH
microscopy)
other cause(s).
Release from care
Cystoscopy
Imaging (CTU)
years.
Release from care
nephrologic causes
+
+
+
+
-
-
-
-
35

LABORATORY TESTING
• Urinalysis
– if not performed previously
– to confirm the presence of hematuria
– check for dysmorphic red cells, cellular casts, or
proteinuria
• Urine culture
– if the urinalysis or clinical presentation suggests infection
• Renal function testing (serum creatinine)
– to determine whether concomitant nephrologic evaluation
is indicated
– to guide the selection of appropriate upper tract imaging
• Prostate-specific antigen in the appropriate setting.
36

CYSTOSCOPY
• Most reliable way to evaluate the bladder for
the presence of bladder cancer
• Provides the opportunity to evaluate the
urethra.
• The AUA guidelines
– all adults who are 35 years of age or older (<1 per
100,000) and/or have risk factors for malignancy.
37

CYSTOSCOPY
Blue-light cystoscopy
• Using 5-aminolevulinic acid (ALA) or
hexylaminolevulinate (HAL) instillation
• Approved by the US FDA for evaluation of
patients with suspicion of papillary bladder
cancer
• Studies supporting its use have been conducted
in patients with known bladder cancer, thereby
limiting generalizability to MH patients
38

CYSTOSCOPY
39

CYSTOSCOPY
Blue-light cystoscopy
• Disadvantages
– rare anaphylactoid shock, hypersensitivity, pain,
cystitis, dysuria, hematuria
– risk for unnecessary biopsies compared with
conventional white light cystoscopy
• AUA guideline recommends against using
blue-light cystoscopy for evaluation of MH
40

UPPER TRACT IMAGING
Multiphasic CT urogram
• CT with precontrast, nephrographic, and
excretory series
• Imaging study recommended by the AUA
• Offers complete imaging of the urinary tract
41

CT UROGRAM
Unenhanced CT scan
42

CT UROGRAM
Cortical
nephrographic phase
• 25 to 80 s after
contrast medium
injection
• Reveals increased
enhancement of
the renal cortex (C)
relative to the
medulla (M).
43

CT UROGRAM
Homogeneous
nephrographic phase
• 85 and 120s after
contrast medium
administration
• reveals a
homogeneous,
uniform, increased
attenuation of the
renal parenchyma.
44

CT UROGRAM
Excretory phase
• 3 minutes after
contrast
medium
administration
• shows contrast
medium in the
RP bilaterally
45

UPPER TRACT IMAGING
Multiphasic CT urogram
• Drawbacks
– may not be appropriate for all patients (e.g.,
pregnancy, iodinated contrast allergy, renal
insufficiency)
– uses a relatively high radiation dose (20–30 mSv)-
risk of carcinogenesis
46

CT UROGRAM
• CT urography is not as sensitive as cystoscopy for
the detection of urothelial tumors in the bladder.
• Only large bladder tumors are visualized with CT
imaging studies as filling defect in the lumen of
the bladder.
• Carcinoma in situ cannot be visualized on CT
scanning and therefore cystoscopy is still an
important part of a comprehensive hematuria
workup.
47

UPPER TRACT IMAGING
• Magnetic resonance (MR) urogram
– In the setting of a contraindication to CT urogram
– contraindication
• Pacemaker
• significant renal function compromise (eGFR <30 and when
the administration of gadolinium risks nephrogenic systemic
fibrosis)
• NC CT or ultrasound, in conjunction with
retrograde pyelography to evaluate the calyces,
renal pelvis, and ureters, may be most
appropriate.
48

UPPER TRACT IMAGING
US plus cystoscopy vs CT urogram plus cystoscopy
• more cost effective
• nearly the same diagnostic yield
• not risk stratified and importantly has not been
prospectively tested
49

Urine Cytology
• Highly sensitive and specific for the detection
of HG urothelial carcinoma, LG- decreased
• Overall
– sensitivity of 15.8% to 54.5%
– specificity of 95.0% to 100% for bladder cancer
detection
50

Urinary Biomarkers
• Nuclear matrix protein-22 (NMP-22)
• Fluorescence in situ hybridization (FISH)
• Immunocytology for CEA and mucin
glycoproteins (ImmunoCyt and CertNDx)
51

Urinary Biomarkers
NMP-22
• Offers a potential advantage in management of
patients with MH: it is available as a point-of-care
test.
• Only two studies have focused on AMH, with one
finding a high sensitivity (90.9%) and the other
demonstrating very low sensitivity (6.0%).
• Specificity was moderate or high in both studies
(76.3% and 82.5%, respectively)
52

Urinary Biomarkers
NMP-22
53

Urinary Biomarkers
FISH
• for abnormalities of chromosomes 3, 7, 17,
and 9p21
• UroVysion
• sensitivity and specificity of 61% and 93%,
respectively, for bladder tumors
54

Urinary Biomarkers
FISH
55

Urinary Biomarkers
Immunocytology
• ImmunoCyt test
– Antibodies directed against
• Mucin glycoprotein- Green
• CEA- Red
– sensitivity of 68.1%- 87%.
56

Urinary Biomarkers
Immunocytology
• CertNDx
– assesses several markers (mutant FGFR3, quantified
MMP-2, and hypermethylation of TWIST1 and NID2).
– Sensitivity- 87.9% and specificity- 56.3%
• A similar test, looking for methylation of TWIST1,
ONECUT2, and OTX1, along with mutation of
FGFR3, TERT, and HRAS
– sensitivity of 93% and specificity of 86%
57

Urinary Biomarkers
• Current evidence
– none can replace cystoscopy or imaging,
– not recommended in the initial evaluation of
patients with AMH
• Cytologic examination may be considered in
– patients with a negative initial workup in whom
urothelial carcinoma is still suspected, as well as in
– patients with symptomatic MH.
58

GUIDELINE-BASED EVALUATION OF MH
Scenarios
• When the cause is diagnosed before complete
evaluation?
• When benign cause is diagnosed, need for
further evaluation?
• When medical Renal disease is diagnosed,
need for further evaluation?
• When the initial evaluation is negative?
59

GUIDELINE-BASED EVALUATION OF MH
AUA guidelines
Upper tract
imaging
Renal cancer/
ureteral calculus
Cystoscopy
Clearance of
bladder and
urethral
pathology 60

WHEN BENIGN CAUSE IS DIAGNOSED
ensure that the hematuria has resolved in the absence of the presumed benign cause
urine should be retested
cause should be verified and treated
benign cause of hematuria is discovered (e.g., UTI)
Initial history and physical examination
61

WHEN MRD IS DIAGNOSED
• If a medical renal cause of hematuria is
suspected based on the presence of renal
insufficiency, hypertension, or abnormalities
on urinalysis, nephrology evaluation is
recommended, but the patient should still
undergo urologic evaluation.
62

Natural History of MH With a -ve Initial
Evaluation
AUA Recommendation-
Negative workup
following up annual
urinalysis for 2 years
urinalyses confirm
resolution of hematuria
releasing the patient
from care
Persistent/recurrent
AMH or for development
of symptoms or GH
repeating the hematuria
evaluation within 3 to 5
years
63

64

+AMH
microscopy)
other cause(s).
Release from care
Cystoscopy
Imaging (CTU)
years.
Release from care
nephrologic causes
+
+
+
+
-
-
-
-
65

SYMPTOMATIC MH
• Differential diagnosis- same as AMH.
• Risk for malignancy may be significantly higher
than in AMH (10.5% vs. 5.0% or less)
• Complete workup can be avoided
– In the setting of a symptomatic, culture-
documented urinary infection presenting with
hematuria, with documentation of hematuria
resolution after treatment
66

SYMPTOMATIC MH
AUA guidelines (Changes from AMH)
• Cystoscopy is recommended in such patients
regardless of age
• Urine cytologic examination is considered an
option in the setting of irritative voiding
symptoms
67

GROSS HEMATURIA
• As the degree of hematuria increases, so does
the likelihood of finding clinically significant
lesions during evaluation
• 50% -demonstrable cause
• 20% to 25% - urologic malignancy, most
commonly bladder cancer and kidney cancer
68

GROSS HEMATURIA
• Recommended evaluation
– urine cytologic examination
– Cystoscopy
– upper tract imaging, preferably CT urogram
• Exception
– antecedent trauma
– culture-documented UTI
69

GROSS HEMATURIA
• GH must be assessed for hemodynamic
stability with careful attention to
– vital signs, anemia with a complete blood count
• For patients on anticoagulation
– coagulation parameters to ensure that levels are
within the therapeutic range.
• After initial stabilization, diagnostic evaluation
should then proceed, with cause-specific
management.
70

HEMORRHAGIC CYSTITIS
• Intractable hematuria localizing to the bladder
• Characterized by diffuse inflammation and
bleeding from the bladder mucosa
• Unfortunately, patients in this situation are
often elderly and infirm, with medical
comorbidities that complicate plans for care
transient condition
that quickly resolves
after conservative
management
life-threatening
condition requiring
urgent intervention
71

72

Bacterial infections
• common cause of GH
• symptomatic resolution typically noted after
appropriate treatment
73

Viral-induced hemorrhagic cystitis
• may affect children and immunosuppressed adults
particularly (e.g., after renal or bone marrow
transplantation).
• BK virus
– member of the polyomavirus family, is the most common virus
• Adenovirus
– types 11 and 35
– correlated with HC in children and renal transplant patients
• Treatment
– primarily supportive, with hydration, diuresis, and bladder
irrigation, although case reports of success with antiviral
therapy exist
74

Oxazaphosphorine class of chemotherapeutic
agents
• Specifically cyclophosphamide and ifosfamide.
• Occur in 2% to 40% of patients treated with
cyclophosphamide
• Dose dependent.
75

Onset of hematuria is typically within 48 hours of treatment
Subsequent tissue edema/fibrosis
Stimulates bladder mucosal sloughing
Excreted in kidney
Production of metabolite acroline in liver
Cyclophosphamide
76

Treatment
• 2-Mercaptoethane sulfonate (mesna)
– binds to acrolein and renders it inert
– For prophylaxis against cyclophosphamide-induced HC
– 10% to 40% -develop HC despite preventive treatment.
• Hyperhydration with forced diuresis and/or
continuous bladder irrigation
– Debate continues: mesna is more effective?
77

Radiation therapy for pelvic malignancy
represents
• Moderate to severe hematuria- 5% of patients
• Depend on
– radiation dosage
– mode of delivery
• onset between 6 months and 10 years after
treatment
78

Further compromising tissue healing
Secondary infection frequently ensues
Local vascular compromise
Tissue necrosis and mucosal sloughing
Progressive obliterative endarteritis
Induce inflammation, fibrosis, and ischemia
Radiation damages the vascular endothelium,
79

Receipt of both cyclophosphamide
chemotherapy and pelvic radiation
• Represents risk factors for bladder cancer
• Such patients presenting with hematuria
should be evaluated for bladder cancer before
the diagnosis of hemorrhagic cystitis is
assigned
80

Cystectomy (with conduit uninary diversion)
Internal iliac artery angioembolization
Formalin 4%
(repeat pre-Tx cystogram)
Formalin 1%
Obtain pre-Tx cystogram
Hyperbaric Oxygen Therapy (HBOT)
Continue supportive measures
• Add bilateral nephrostomy tubes for diversion of urine if hematuria continues, ± bilateral nephro-occlusive tubes
Hematuria continues after 48 hours
Initial management
• Hydration/diuresis
• Cystoscopy with clot evacuation ± fulguration, biopsy if concern for malignancy
• Continuous bladder irrigation
• Supportive care (transfusion prn)
• Address “correctable” factors (infection, coagulopathy, tumor)
• Intravesical alum, PG, Na hyaluronate, Silver Nitrate, Aminocaproic acid
Diagnose hemorrhagic cystitis
• Patient with identified risk factors
• Hematuria evaluation (UT imaging, urine cytology, urine culture)
81

HEMORRHAGIC CYSTITIS- MANAGEMENT
Initial management- Intravesical agents
• Alum
• Prostaglandins
• sodium hyaluronate
• Silver nitrate
• Aminocaproic acid
82

Alum
• Aluminum ammonium sulfate or aluminum
potassium sulfate
• In small series, widely variable success rates
(e.g., 45% to 100%), with limited durability of
hematuria control, have been reported after
alum instillation
83

• used to irrigate the bladder at a rate of 200 to 300 mL/h.
1% alum solution
5L
sterile
water
50g
alum
84

Arrest bleeding
stimulate vasoconstriction and a decrease in capillary permeability
cause protein precipitation on the urothelial lining
Alum- Irrigation
85

Drawbacks
• Suprapubic discomfort and bladder spasms
• Systemic absorption
– aluminum toxicity, with consequent mental status
changes, particularly among patients with renal
insufficiency.
86

Advantages
• Cell penetration and therefore overall toxicity of
this agent are low
• Instilled without anesthesia
• Overall relatively favorable efficacy and safety
profiles.
• Considered for first-line intravesical therapy
among patients failing initial supportive
measures, particularly among those without
renal insufficiency.
87

Prostaglandins
• Carboprost tromethamine [PGF2-α])
• Precise mechanism of activity remains unclear,
– Thought to cause vasoconstriction
– platelet aggregation
– cytoprotection via mucous barrier regulation.
• Response rates of 50% to 60% have been noted
• Difficulties with PGF2 access, storage, and high
costs have limited generalized utility
88

Intravesical sodium hyaluronate
• As a defect in the bladder’s glycosaminoglycan
layer has been thought to contribute to the
pathogenesis of hemorrhagic cystitis
• Noted symptomatic improvement
89

Intravesical Silver nitrate
• Result in chemical coagulation at bleeding
sites.
• A 0.5% to 1% solution is instilled for 10 to 20
minutes
• The potential for precipitation and upper tract
obstruction with this agent led to the
recommendation for a cystogram to rule out
reflux before administration
90

Intravesical Aminocaproic acid
• A lysine analogue
• Competitive inhibitor of activators of
plasminogen, including urokinase
– thus interrupts fibrinolysis and the cascade that
perpetuates hemorrhage
• Continuous bladder irrigation with 200 mg
aminocaproic acid/L of 0.9% normal saline has
been described
• Irrigation continued for 24 hours after hematuria
resolves.
91

Intravesical Aminocaproic acid
• Symptom resolution- 92% of patients
• The risk for thromboembolic events may be
increased with this treatment
• Given only after the bladder has been
rendered clot free, because the agent will
otherwise lead to the formation of hard clots
difficult to eradicate from the bladder
92

Formalin 4%
Formalin 1%
Initial management
93

Hyperbaric oxygen therapy (HBOT)
• When Hematuria remains refractory to the
aforementioned measures
• Particularly with hemorrhagic cystitis resulting
from radiation therapy or cyclophosphamide
treatment
• HBOT is carried out in a specially designed
chamber
94

Hyperbaric oxygen therapy (HBOT)
• Involves administration of
– 100% oxygen
– Pressure- 2 to 3 atmospheres
– Duration- appr. 90 minutes
– 30 to 40 sessions
• Response rates- 80% to 90%
– maintained up to 2 ½ years after treatment.
• 5-year complete response rate- only 27%
95

• HBOT
• local tissue oxygen tension increases
• oxygen extraction by tissues increases
• Diminish edema and promote neovascularization
• critical steps in the wound healing process
96

• Complications
– claustrophobia (20%), otalgia (17%), and, rarely,
seizures
• Bilateral nephrostomy tube insertion, with or
without occlusion of the ureters
– For patients with continued bleeding during therapy
– to decrease exposure of the hemorrhagic bladder to
urokinase and thereby theoretically facilitate
hemostasis, particularly during the relatively
prolonged time course of HBOT
97

Formalin 4%
Formalin 1%
Initial management
98

Intravesical formalin
• Induces cellular protein precipitation and
capillary occlusion.
• Control of bleeding- 80% to 90% of cases,
which are relatively higher rates than other
intravesical treatments.
• May induce significant pain, administration
under general or spinal anesthesia is
recommended
99

Complications
• Bladder fibrosis with associated decreased
bladder capacity
• Ureteral stricturing with proximal
hydronephrosis/renal injury
• Thus pretreatment cystogram is recommended to
exclude the presence of vesicoureteral reflux
and/or bladder perforation
• Patients must be counseled regarding the
potential impact on subsequent bladder function
100

If reflux is documented,
• placement of occlusive ureteral catheters is
recommended to limit upper tract exposure to
the medication.
• Low concentrations of formalin (1% to 4%)
should be used
101

Instillation
• Volume
– up to 300 mL or to bladder capacity
• Should be done under gravity
– catheter no more than 15 cm above the pubic symphysis.
• Instillation should be limited to 10 to 15 minutes
• Should be performed with the catheter on light
traction to prevent urethral exposure
• Care taken to protect all external areas of skin from
exposure.
102

Intravesical Formalin
• Given the potential toxicities of formalin,
together with the requirement for
administration under anesthesia, this agent
should be reserved for second-line therapy
103

Formalin 4%
Formalin 1%
Initial management
104

• Performed unilaterally or bilaterally
• Can be done even in debilitated patients, with
relatively limited risk
• Selective embolization of the anterior branch of
the internal iliac artery bilaterally is typically
required to achieve hemostasis
• May use any of a variety of embolic materials,
including gelatin microspheres, polyvinyl alcohol
particles, or coils
105

• Initial hemorrhage control- 90%
– durability of response- not been well established
• Reliability of this approach for patients after
radiation therapy in which mucosal ischemia
underlies the pathophysiology, remains
uncertain
106

• Complication: embolization of the posterior branch of
the internal iliac artery
• occlusion of the superior gluteal artery
• Gluteal muscle ischaemia
• significant gluteal pain.
107

Cystectomy with urinary diversion
• In the setting of failed angioembolization and
other conservative approaches
• Supravesical urinary diversion alone (e.g., ileal
conduit) without cystectomy
– Complications- up to 80% of patients with a retained
bladder
– specifically infection (pyocystis), with rehospitalization
in 43%
– suggesting that cystectomy should be performed at
the time of urinary diversion if feasible
108

• Typically elderly, infirm
– in poor condition for surgery.
• Perioperative complication rates
– significantly higher than what has been reported
after cystectomy for bladder cancer
• Balance the risks and benefits
109

HEMATURIA FROM PROSTATIC ORIGIN
• Diagnosis made after a complete GH
evaluation (including cytology, upper tract
imaging, and cystoscopy) to confirm that no
other source of hematuria exists
transient self-limiting
episodes Continuous bleeding
resulting in the obstruction
of urinary flow and in
transfusion dependence
110

Commonly due to
• BPH
• prostate-related infection (prostatitis)
• prostate cancer
111

Prostate-related gross
hematuria
• Exclude other causes of hematuria
with UT imaging, urine cytology,
cystoscopy
Initial management
• Hydration/diuresis • Continuous
bladder irrigation • Supportive care
(transfusion prn)
• Address “correctable” factors (i.e.,
coagulopathy)
BPH
5 Alpha reductase
inhibitor
Clinical/comorbidity
status poor?
Cystoscopy with
fulguration
• Consider antiandrogen
therapy
Angioembolisation
BPH-related surgery
• HOLEP • TURP •
Simple • PVP
prostatectomy
Angioembolisation
Prostatitis
• Diagnose by clinical presentation
+ urine culture
Antibiotic therapy
Prostate cancer
(typically advanced)
Androgen deprivation
therapy ± external
beam radiotherapy
Cystoscopy with
fulguration/“channel”
TURP
Urinary diversion (pending
clinical status)
• Percutaneous nephrostomy
tube • Palliative prostatectomy/
cystoprostatectomy with conduit
diversion
Angioembolisation
112

BPH
• Most common cause of prostate-related
bleeding
• Most common cause of GH in men older than
60 years
• Only pathological condition identified in
approximately 20% of cases from hematuria
studies .
113

•Benign Prostatic hyperplasia
•Higher levels of VEGF
•Higher microvessel density
•Increased prostatic vascularity
•Prone to Haematuria
114

HEMATURIA IN BPH- MANAGEMENT
• Expectant management with hydration
– Usually mild and selflimiting.
• Surgery
– Historically - indication for surgery
– increased understanding of the molecular
pathway contributing to the pathophysiologic
process
– targeted medical therapy
115

Estrogens and antiandrogens
• Decreases prostate bleeding
• MOA- presumably
– through the repression of androgen-stimulated
angiogenesis and
– the induction of programmed cell death within
the prostate
116

Finasteride,
• 5α-reductase inhibitor that blocks conversion of
testosterone to dihydrotestosterone
• Treatment of outlet obstructive symptoms
• Investigated extensively for BPH-related
haematuria
• MOA- associated with decreased
– VEGF expression,
– prostate microvessel density
– prostatic blood flow
117

• Demonstrated efficacy even in patients being
treated with anticoagulation.
• Symptom improvement or resolution- 90%
• Onset of action
– Variable
– improvement in bleeding noted from as short as 2
weeks to up to 9 months after initiating therapy
• Who eventually require BPH surgery, concurrent
therapy with 5α-reductase inhibitors can
decrease perioperative bleeding complications
and morbidity
118

TURP
• Patients with persistent bleeding from BPH
despite conservative therapies and/or
endoscopic fulguration
• Particularly when additional indications for
BPH surgery coexist
• Alternative
– Photoselective vaporization of the prostate
– Holmium laser enucleation of the prostate
– Suprapubic/retropubic prostatectomy
119

Selective prostatic artery embolization (PAE)
• Persistent bleeding despite TURP
• Typically bilateral embolization is performed
• Initial success- 90%
• Recurrence in 15% to 28%
120

Selective prostatic artery embolization (PAE)
• Superselective approach
– specifically addressing the Prostatic arteries with
gelatin microparticles
• Selective approach
– embolization of the anterior branch of the internal
iliac artery has been used as well
121

Selective prostatic artery
embolization (PAE)
Type I- Origin from anterior
division of IIA in a common
trunk with the superior
vesical artery (SVA)
Type II- Origin from
anterior division of IIA,
inferiorly to SVA
Type III- Origin from
obturator artery
Type IV- Origin from
internal pudendal artery
Type V- Less common
origins
122

Radical prostatectomy or cystoprostatectomy
• Must be considered
• But usually are poor surgical candidates
because of comorbidity status
123

Prostatitis
• Traditionally secondary to bacterial infection
• Hematuria as the manifesting symptom in 2.5% of men
• The mechanism of hematuria in prostatitis
– unclear and may be related to inflammation
• Management
– Antibiotics when culture-documented bacterial prostatitis
is present.
– Significant recurrent hematuria in the setting of
nonbacterial prostatitis is relatively uncommon
• antibiotics in addition to standard supportive measures
124

HEMATURIA FROM PROSTATE CA
Prostate cancer
• Hematuria typically results in cases of
significantly locally advanced tumors, often
with bladder base/trigonal invasion.
• Most common local symptom among patients
with advanced symptomatic prostate cancers
• Exclude- hemorrhagic cystitis from radiation
therapy
125

Management
• Primarily with palliative intent
– tumors are typically invasive of the bladder and/or
pelvic sidewall (T4)
– patients are often elderly and unwell.
• Initial conservative measures
– catheter drainage with or without continuous bladder
irrigation, suffice for most cases of mild prostatic
bleeding.
126

Management
• Palliative external beam radiotherapy
– For patients in whom hematuria is not acutely life
threatening
– patients who are radiation naïve with or without
androgen deprivation therapy may be administered
• Androgen deprivation therapy
– patients who are not candidates for local therapy
– among patients in whom disease has recurred after
previous local therapy
127

Surgery
• Persistent hematuria in the setting of BOO
• Cystoscopy under anesthesia with fulguration
and/or limited, or channel, transurethral
resection of prostatic tissue should be
undertaken.
128

• Selective angioembolization
– Data on this approach in the setting of prostatic
malignancy are scant and have demonstrated limited
durability of bleeding control
• Urinary diversion
– Initially may be attempted with PCN tube insertion
• Palliative extirpative surgery
– Radical prostatectomy/ cystoprostatectomy and
conduit diversion
– Considered, pending patients’ clinical and comorbidity
status.
129

URETHRAL BLEEDING
• Urethral bleeding (urethrorrhagia) is defined
as bleeding emanating from the urethra at a
point distal to the bladder neck, occurring
separate from micturition
• Careful history and physical examination
– blood at the urethral meatus in the absence of
volitional micturition
– initial hematuria
• Implies pathological processes distal to the
external urinary sphincter 130

URETHRAL BLEEDING
• Women
– differentiating bleeding from gynecologic origin
– based on history alone may be challenging
– pelvic examination is typically necessary to clarify
the site of origin
131

URETHRAL BLEEDING
Diagnosis
• Retrograde urethrogram
• Cystourethroscopy
– direct visualization permits identification of
pathological processes in the urethra
– biopsy and fulguration allow for histologic
characterization and cessation of bleeding.
132

133

URETHRAL BLEEDING
Trauma
• Most common cause of urethral bleeding.
• Example
– blunt trauma via straddle injury, kick to the
perineum, or pelvic fracture
– Foreign body insertion
– Penile fracture
134

URETHRAL BLEEDING
Trauma
• Perineal or penile bruising, accompanied by a
hematoma, often is a clear indication of injury
related to trauma.
• Retrograde urethrography is essential in
instances of trauma when a urethral injury is
suspected
135

URETHRAL BLEEDING
Urethritis
• Refers to infection or inflammation of the
epithelial lining of the urethra
• Has been reported secondary to
– bacterial or viral infection
– chemical irritants (i.e., spermicidal jelly),
– Medication related (i.e. amiodarone)
– autoimmune systemic conditions (HLA-B27
reactive arthritis)
136

URETHRAL BLEEDING
Urethritis
• Urethral discharge on palpation may be noted
with urethritis in men.
• Urine microscopy and cultures, as well as
urethral swabs for causative organisms,
represent essential components of the
evaluation.
137

URETHRAL BLEEDING
• Urethral tumors
– Rare
– blood per meatus may be a manifesting sign
– specifically in men who have undergone a
radical cystectomy with urethra still in situ
• Urethral caruncles
– benign urethral lesions typically originating from the posterior lip of the
urethra
– most commonly found in postmenopausal women
– These lesions are thought to arise from prolapse of distal urethra as a
consequence of estrogen deficiency.
• Urethral diverticulum
– classic presentation of dysuria, dyspareunia, and dribbling
– May also report intermittent episodes of bleeding
– urethral discharge may be noted on examination
138

HEMATURIA FROM THE UPPER TRACT
• Frequently asymptomatic
• “Clot colic”
– macroscopic bleeding with clots can result in
subsequent ureteral obstruction
• Anemia, and even rarely hemodynamic
instability
• Manifests as total hematuria
• Characterized by wormlike clots passed via the
urethra
139

140

MEDICAL RENAL DISEASE
Glomerular diseases
• Constellation of acquired or inherited conditions
in which the glomeruli are damaged.
• Consequences include loss of
– RBCs and protein in the urine
• Clinical sequelae
– Hematuria
– hypoproteinemia with associated edema
– reduced glomerular filtration rate.
• Urinary findings suggestive of a glomerular cause
– RBC casts in the urinary sediment, dysmorphic RBCs
– proteinuria 141

DIAGNOSIS
INVESTIGATION
HISTORY
GLOMERULAR
HEMATURIA
Rash,
arthritis
↑ C3, C4,
ANA
SLE
Hemoptysis
Bleeding
tendency
Microcytic
anemia
Goodpasture
syndrome
Recent URTI or
skin
infection/rash
↑ ASO titer,
C3 level
PSGN
Related to
exercise
+ Renal
biopsy for
IgA, IgG, β1c-
globulin
IgA
nephropathy
(Berger
disease)
Family history
of hematuria
and/or abn UA
Deafness
Alport
nephritis
No other
symptoms/
signs
Renal biopsy
Mesangioproliferati
ve,
mesangiocapillary,
or
Membranous GN
142

Tubulointerstitial diseases
• Broadly refer to kidney diseases affecting
structures in the kidney outside the glomerulus.
• Sickle cell nephropathy
– sickled erythrocytes decrease medullary blood flow,
causing local ischemia, microinfarction, and papillary
necrosis
• Analgesic nephropathy
– cause renal papillary necrosis and subsequently
chronic interstitial nephritis
143

Diagnosis and Management
• Percutaneous renal biopsy
– valuable diagnostic modality in case of a suspicion
for glomerular or tubulointerstitial causes of
hematuria.
• Current guidelines advocate completion of the
hematuria evaluation even when medical
renal causes are suspected
144

VASCULAR CONDITIONS
• Causes:
– Renal AVM, Aneurysm, Nutcracker syndrome
• Predisposing factors
– pelvic or vascular surgery, pelvic irradiation, extensive
ureteral mobilization, and chronic ureteral stenting
• Management
– high mortality rates have been reported with surgical
repair of ureteroiliac fistulas
– angiographic localization with vascular stenting has
become the current preferred management approach
145

VASCULAR CONDITIONS
Renal arteriovenous malformations (AVMs)
• Abnormal communications between
intrarenal arterial and venous systems
• Causes
– congenital and acquired (iatrogenic)
• Acquired AVMs
– account for 75% of such cases
– associated with renal biopsy, renal surgery (partial
nephrectomy, nephrolithotomy), and trauma
146

VASCULAR CONDITIONS
Renal arteriovenous malformations (AVMs)
• Arteriography with selective angioembolization
– primary diagnostic and therapeutic option
– afford symptom resolution with maximal preservation
of functional renal parenchyma.
– Thus expeditious angiography should be considered
for patients with a recent history of a renal procedure
presenting with GH.
– The goal of AVM embolization is occlusion of the site
where abnormal arterial and venous communication
exists
147

VASCULAR CONDITIONS
Renal artery aneurysms
• May be related to connective tissue disorders
• Generally asymptomatic.
– Hypertension may be present in up to 90% of affected
persons
– Dissecting aneurysms may cause flank pain with GH
• Management
– initially with blood pressure control
– subsequently via endovascular approaches in the
refractory albeit hemodynamically stable patient
– surgical intervention is typically necessary in the unstable
patient
148

VASCULAR CONDITIONS
• “Nutcracker phenomenon”
– compression of the left renal vein between the
aorta and superior mesenteric artery
149

VASCULAR CONDITIONS
Haematuria
Blood enters collecting system
Small-volume rupture of thin-walled capillaries into the collecting system
Increase in left renal vein pressure
Compression of left renal vein
“Nutcracker syndrome”
150

VASCULAR CONDITIONS
“Nutcracker syndrome”
• Management
– Surgery: Left renal vein transposition, superior
mesenteric artery transposition, and nephrectomy
– Endovascular stenting to maintain a patent renal
vein has been reported as well.
151

LATERALIZING ESSENTIAL HEMATURIA
• Also termed benign essential hematuria or
chronic unilateral essential hematuria
• Defined as macroscopic hematuria
cystoscopically localized to one side of the
urinary system without a clear identifiable
cause
152

• As such, patients have typically had normal
prior radiographic studies.
• Although rare, may range from minimally
symptomatic GH to clot retention and anemia
• Many such cases no identifiable cause can be
determined
153

• Cystoscopy
– at the time of bleeding may allow lateralization of
the source of hematuria.
• Ureteropyeloscopy
– in the absence of a clear cause for bleeding
localized to the upper tract
– recommended as a diagnostic and potentially
therapeutic modality
154

Critical components of diagnostic ureteropyeloscopy
include
• the judicious use of guidewires (to avoid inadvertent
urothelial injury),
• low-pressure irrigation
• systematic evaluation of all calices from a superior to-
inferior approach
• Biopsy samples can be obtained for lesions suspicious
for malignancy
• fulguration of such tumors or other noted sources of
bleeding (i.e., hemangioma) can be accomplished as
well.
155

Hematuria - evaluation and management

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