This document provides guidance on evaluating hematuria. It defines different types of hematuria and discusses differential diagnoses. Microscopic hematuria should be evaluated if 3 or more red blood cells are present per high power field on urinalysis. Evaluation includes history, physical exam, urinalysis, cystoscopy, upper tract imaging and consideration of urine cytology. Gross hematuria or risk factors like older age or smoking increase likelihood of malignancy and warrant full evaluation. Causes of hematuria can originate from the bladder, prostate, upper urinary tract or medical renal diseases. Management depends on identified cause but aims to resolve bleeding and rule out malignancy with follow up testing.

1. HAEMATURIA ; HOW TO
EVALUATE

2. • Sign of “potentially” important illness
• Knowledge of differential diagnosis, principles
of evaluation, and strategies for management
is critical.

3. CLASSIFICATION AND TIMING OF
HEMATURIA
Hematuria
Gross/visible
Initial Urethral source
Terminal
Bladder trigone,
bladder neck,
prostate
Total Bladder or above
Microscopic
Asymptomatic
Symptomatic

4. Gross haematuria to be differentiated
from
• Pigmenturia
– Endogenous sources (e.g., bilirubin, myoglobin,
porphyrins)
– Foods ingested (e.g., beets and rhubarb)
– Drugs (e.g., phenazopyridine)
– Simple dehydration
• Vaginal bleeding

5. MICROSCOPIC HEMATURIA
• Prevalenceof approximately 6.5% of adults
(healthy participants), varying according to
the characteristics of the population.
• Malignancy has been detected in ≈ 4%of
patients of asymptomatic MH
– Higher rates in studies with a predominance of
• Males
• Older patients
• Smokers
• Higher degrees of MH

6. Criteria for the Diagnosis of
Microhematuria
• AUA guideline panel defined MH as three or more
RBCs/HPF,
• Why 3 ?
• Higher thresholds would lead to missed opportunities
to diagnose treatable urologic conditions.
• MH caused by significant medical conditions, such as
urinary
tract malignancy, can be intermittent.

7. How many urine routine do we need ?
• AUA guideline panel has determined that a
single positive urinalysis is sufficient to
prompt evaluation
• Rate of malignancy detected among patients
evaluated for a single positive urinalysis was
3.6%.

8. Dipstick vs urine routine?
• Benzidine detect peroxidase activity of
hemoglobin
• Myoglobinuria - false +ve
• Urine dipstick tests must be confirmed on
urinalysis with microscopy and
• Alone are insufficient to prompt an
evaluation.

9. Fallacies of urine routine
• False negative- dilute urine (osmolality <308
mOsm) – RBC lysis
• Falsely positive - immediately after
– Prolonged recumbence (first void in morning)
– After vigorous physical or
– After vigorous Sexual activity

10. Evaluation of Patients with ”A”
Microhematuria - Differential
Diagnosis
• 30- 60% patients evaluated for MH have a
demonstrable cause
• Evaluation of MH yields a diagnosis of
malignancy in 1.8- 4.3%
– Higher with higher levels of microscopic hematuria
(>25 RBCs/HPH), GH, or risk factors for malignancy
• BEP (12.9%), Calculus (6.0%), urethral stricture
(1.4%)

11. CATEGORY EXAMPLES COMMON CLINICAL PRESENTATION AND RISK
FACTORS
Congenital or acquired
anatomic abnormality
Polycystic kidney disease
Ureteropelvic junction obstruction
Ureteral stricture
Urethral diverticulum
Fistula
Family history of renal cystic disease
History of UTI, stone, flank pain
History of surgery or radiation, flank pain,
hydronephrosis;
stranguria, spraying urine
Discharge, dribbling, dyspareunia, history of UTI,
female
predominance
Pneumaturia, fecaluria, abdominal pain, recurrent
UTI, history of
diverticulitis or colon cancer
Infection/inflammation Any
Cystitis
Pyelonephritis
Urethritis
Tuberculosis
Schistosomiasis
Hemorrhagic cystitis
History of infection
Female predominance, dysuria
Fever, flank pain, diabetes, female predominance
Exposure to sexually transmitted infections,
urethral discharge,
dysuria
Travel to endemic areas
Travel to endemic areas
Calculus
Neoplasm GU
Benign prostatic enlargement
Medical renal disease† Hypertension, azotaemia, dysmorphic
erythrocytes, cellular casts,
proteinuria
Other Exercise-induced hematuria‡
Endometriosis
Hematologic or thrombotic disease
Recent vigorous exercise
Cyclic hematuria in a menstruating woman
Family history of personal history of bleeding or

12. Selecting Patients for Evaluation of
Microhematuria
• Benign vs malignant
• 60-30 % of patients with AMH will have a
negative haematuria evaluation
• Haematuria Risk Index to predict cancer risk (0
- 11 points)
– History of gross haematuria, age ≥ 50 years- 4
points
– Smoking, male sex, and >25 RBC/HPF on recent
urinalysis- 1 point.
Haematuria Risk Index Cancer risk
LOW RISK (0 to 4 points) 0 to 0.3%
INTERMEDIATE RISK (5 to 8
points)
1.1% to 2.5%
HIGH RISK (9 to 11 points) 10.7% to 11.6%
Kaiser Permanente

14. What AUA says ?
• No uniform agreement on how to identify benign
causes
• < 25% of patients with hematuria are referred for
evaluation and <10% undergo a complete evaluation,
even among patients at high risk for malignancy
• Recommend evaluating patients with AMH “in the
absence of an obvious benign cause” such as infection
and menstruation

15. • Infection should be confirmed with a urine culture and the
urinalysis should be repeated after treatment of the UTI to
document resolution of the hematuria.
– If haematuria persists, further evaluation is warranted
• Patients who develop hematuria (microscopic or gross) while
on anticoagulation/ antiplatelet medications /nonsteroidal
anti-inflammatory agents, should undergo a complete
evaluation in the same manner as patients not taking such
medications, because
– Prevalence of hematuria, as well as the likelihood of finding
genitourinary cancers, is same
– These medications may unmask genitourinary lesions at an earlier
stage
– 82% of anticoagulated male patients with GH had significant
urologic lesions and 13.9% of lesions were malignant

16. Evaluation algorithm AMH- AUA
guidelines
• Recommendation-
– Patients meeting criteria for evaluation undergo a
complete evaluation, even if one phase of the
evaluation shows a suspected cause for the MH.
• For example, a patient found to have a kidney
tumor or stone disease during initial workup of
MH should still undergo cystoscopy for
clearance of bladder and urethral pathologic
processes.

17. • History- urologic history , associated
symptoms, general medical
history, medication use, Family history,
smoking
• Physical examination-identify signs of
coagulopathy
• Laboratory testing –
– Urinalysis- dysmorphic red cells, cellular
casts, or proteinuria
– RFT
– PSA

18. • Cystoscopy in the Diagnostic Evaluation of
Hematuria
– Most reliable way to evaluate the bladder & urethra
– Should be performed in all adults who meet criteria for
hematuria evaluation who are 35 years of age or older and/or
have risk factors for malignancy.
• White light vs blue light ?
– Small incremental risk with ALA or HAL and blue-light
cystoscopy (rare anaphylactoid shock, hypersensitivity, pain,
cystitis, dysuria, hematuria)
– Risk for unnecessary biopsies
• AUA recommends against blue-light cystoscopy for
evaluation of MH

19. • Upper Tract Imaging
• Recommendation- Multiphasic CT urogram (precontrast, nephrographic,
and excretory series) is the imaging study of choice for asymptomatic
MH
• Highest sensitivity and specificity for detecting lesions of renal
parenchyma and upper tracts
• Contraindication to CTU- Do MRU with contrast
• Contraindication to magnetic resonance imaging (e.g., pacemaker), eGFR
<30)- noncontrast CT or ultrasound, in conjunction with retrograde
pyelography

20. • Urine Cytology in the Diagnostic Evaluation of Hematuria
• Highly sensitive and specific for high-grade urothelial carcinoma,
but sensitivity decreases significantly for low-grade urothelial
carcinoma,
• Overall sensitivity 15.8- 54.5%, and specificity 95.0- 100% for
bladder cancer detection
• Recommendation - cytological 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.

21. • Urinary Biomarkers in the Diagnostic Evaluation
of Hematuria
• Cleared by the FDA for detection and surveillance
of bladder cancer
• Few studies conducted to evaluate markers in MH
without h/o bladder ca
– Nuclear matrix protein-22 (NMP- 22),
– Bladder tumor antigen,
– UroVysion- FISH for abnormalities of chr 3, 7,
17, and 9p21- sensitivity and specificity high for
upper tract tumors
– Immunocytology for carcinoembryonic antigen
– Mucin glycoproteins ImmunoCyt
– CertNDx- assesses several markers (mutant
FGFR3, [MMP2], and hypermethylation of

22. What happens to negative initial
evaluation – Natural history ?
• MH resolves in one third of these patients over a
period of 3 months to several years
• ≈3 % may develop malignancies
• However absent high-quality evidence
• Recommendation-
– Annual urinalysis for 2 years after a complete negative
hematuria workup
– Releasing the patient from care if the urinalyses
confirm resolution of hematuria
– Repeating the hematuria evaluation within 3 - 5 years
in
• Persistent or recurrent asymptomatic MH or
• Development of symptoms or
• GH

24. SYMPTOMATIC MICROSCOPIC
HEMATURIA
• The DD for symptomatic MH is same as
asymptomatic MH
• Risk for malignancy is significantly higher
(10.5% vs. 5.0% or less)
• Avoid Complete workup if hematuria resolves
after management of benign cause
• Other wise complete evaluation
• Modifications to the recommendations for
evaluation
– Cystoscopy is recommended regardless of age

25. • Recommendation-
• If a benign cause of hematuria is discovered during the initial
history and physical (e.g., UTI), that cause should be verified and
treated and then the urine should be retested to ensure that the
hematuria has resolved in the absence of the presumed benign
cause.
• 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

26. GROSS HEMATURIA
• Differential diagnosis for GH remains the same as for
MH.
• As degree of hematuria increases, so does the
likelihood of finding clinically significant lesions
• 50% have a demonstrable cause, with 20- 25% have
urologic malignancy, MC -bladder and kidney cancer
• GH in culture-documented UTI should have the
infection treated and then a follow-up urinalysis
obtained to ensure clearance
• Recommendation- GH in the absence of antecedent
trauma or culture-documented UTI evaluated with
cytological examination,
cystoscopy, and upper tract imaging, preferably CT
urogram.

27. LOOKING AT SOME SPECIFIC CAUSES

28. HEMORRHAGIC CYSTITIS
• Intractable hematuria localizing to the bladder
• Transient condition to life-threatening condition
• Diagnosis made after a complete GH evaluation
• Characterized by diffuse inflammation and
bleeding from bladder mucosa
• Causes –
– Bacterial infections
– Viral-induced hemorrhagic cystitis-
• BK virus(MC) & adenovirus, particularly
types 11 and 35 associated with
hemorrhagic cystitis
• Children and immunosuppressed adults
following renal or bone marrow

29. • (Oxazaphosphorine ) cyclophosphamide and ifosfamide-
– Occur in 2% to 40% of patients
– Dose dependent
– Acrolein from liver-> bladder mucosal sloughing and
subsequent tissue oedema/ fibrosis
– 2-Mercaptoethane sulfonate (mesna), binds to acrolein
and renders it inert, suggested for prophylaxis
– 10% to 40% of patients will develop the condition despite
mesna
– Hyper hydration with forced diuresis and/or continuous
bladder irrigation
• Radiation therapy for pelvic malignancy
– Radiation damages the vascular endothelium-> ischemia,
with tissue necrosis and mucosal sloughing occurring
through progressive obliterative endarteritis

30. D/d

31. • Management of Hemorrhagic Cystitis
• In most cases no cause-directed therapy can be offered
and a sequential approach is undertaken
• Increasing urine output via hydration/ diuresis,
catheter placement with continuous bladder irrigation,
SOS transfusion
• Cystoscopy under anaesthesia with clot evacuation and
fulguration of discrete bleeding sites

32. (anterior branch)
(urokinase)

33. AGENT MOA PREPARATION IRRIGATION
RATE
SUCCESS ADVANTAGE DISADVANTAGES
ALUM [1st line]
(aluminium ammonium
sulphate or aluminium
potassium sulphate)
.astringent .protein
precipitation
.vasoconstriction
.decrease capillary
permeability
Dissolve 50 g in 5-L
sterile water [1% alum
solution]
@ 200 to 300
mL/hr
66% to
100%
Anaesthesia
not required
CKD (Aluminium toxicity)
Prostaglandins (e.g.,
carboprost
tromethamine
[PGF2-α]
vasoconstriction,
platelet aggregation,
and cytoprotection via
mucous barrier
regulation
50-60 % storage, and high costs
silver nitrate chemical coagulation 0.5% to 1% solution
instilled for 10 - 20
minutes
precipitation and upper
tract obstruction
(cystogram to rule
out reflux )
Aminocaproic acid competitive
inhibitor of activators of
plasminogen,
(urokinase)
200 mg aminocaproic
acid/L of 0.9% normal
saline
irrigation
continued for
24 hours after
hematuria
resolves
92% thromboembolic events
forms hard clots (give in
clot free bladder)
Formalin
2nd line
protein precipitation
and capillary occlusion
1% to 2%
under gravity, with
the catheter no more
than 15 cm above the
pubic symphysis.
limited to 10 to 15
minutes
performed with
catheter traction to
prevent urethral
exposure
300 mL or to
bladder
capacity
80% to 90% GA/SA (severe pain)
bladder fibrosis decreased
bladder
capacity and ureteral
stricture with proximal
hydronephrosis/
renal injury (cystogram to
rule
out reflux )

34. HEMATURIA FROM PROSTATIC
ORIGIN
• Diagnosis made after a complete GH evaluation
• BPH (MC), prostatitis, or prostate cancer
• Frequently mild and self limiting
• For BPH
– Targeted medical therapy – stop androgen-stimulated
angiogenesis
– Finasteride
• Decreased VEGF, prostate micro vessel density, prostatic
blood flow
• Success rate 90%
• Onset of action is variable, with improvement in bleeding
noted from 2 weeks to up to 9 months
– Limited evidence exists to support the efficacy of Intravesical
agents for BPH-related bleeding
– Persistent bleeding have traditionally been managed TURP
– Persistent bleeding despite TURP, selective angioembolization

35. Bladder base/
trigone
Success rate 81% at
6 weeks
29% final success
rate

37. HEMATURIA ORIGINATING FROM THE
UPPER URINARY TRACT
• Most common causes of hematuria from the
upper urinary tract
including stones, trauma, and malignancy.
• Asymptomatic
• “Clot colic,” as well as anaemia
• Total hematuria
• Wormlike

39. • Medical Renal Disease
– Glomerular diseases
• Hematuria, hypoproteinaemia with
associated oedema, and reduced GFR
• Urinary findings - RBC casts, dysmorphic
RBCs, and proteinuria
– Tubulointerstitial diseases
• Sickle cell nephropathy
• Analgesic nephropathy - papillary necrosis
– Percutaneous renal biopsy

40. • Vascular Conditions Affecting the Urinary Tract
• Ureteroiliac artery fistula
– Pelvic or vascular surgery, pelvic irradiation, extensive ureteral mobilization,
and chronic ureteral stenting
– Angiographic localization with vascular stenting
• Renal arteriovenous malformations (AVMs)
– Acquired AVMs account for 75% (renal biopsy, renal surgery (partial
nephrectomy, nephrolithotomy), and trauma
– Selective angioembolization
• Renal artery aneurysms and pseudo aneurysms
– Managed via endovascular approaches in the hemodynamically stable patient,
– Surgical intervention is typically necessary in the unstable patient
• “Nutcracker syndrome” (renal vein entrapment syndrome) compression of left
renal vein between abdominal aorta and SMA
– Increase in left renal vein pressure causing small-volume rupture of thin-
walled capillaries
– Left renal vein transposition, superior mesenteric artery transposition,
endovascular stenting

41. Evaluation of Upper Urinary Tract Bleeding /
benign essential hematuria or chronic
unilateral essential hematuria
• Macroscopic hematuria cystoscopically localized to one side of urinary
system
• Normal prior radiographic studies
• In many cases no identifiable cause
• H/O - minimally symptomatic GH to clot retention and anaemia
• Direct endoscopic inspection with ureteropyeloscopy is recommended
– Judicious use of guidewires (to avoid inadvertent urothelial injury),
– Low-pressure irrigation
– Systematic evaluation of all calices from a superior-to-inferior approach

42. • THANK U