evaluation of haematuria

1. Evaluation and Management of
Hematuria

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
• Prevalence of 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
Papillary necrosis
Arteriovenous malformation
Renal vein thrombosis
Interstitial cystitis
Trauma
Recent vigorous exercise
Cyclic hematuria in a menstruating woman
Family history of personal history of bleeding or thrombosis
African-American, sickle cell disease, diabetes, analgesic abuse
Voiding symptoms
History

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 group

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 TWIST1 and NID2)
• Variable sensitivity and specificity with very few studies in MH
• Not recommended in the initial evaluation of patients with
asymptomatic MH

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
• Cytological examination is considered an option in the setting of
irritative voiding symptoms

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.
• Recommendations lacking for the follow-up of GH who have non-
diagnostic initial evaluation-> follow-up as for asymptomatic MH

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 transplantation
• Hydration, diuresis, and bladder irrigation , ? Antiviral therapy

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
• Onset between 6 months and 10 years after treatment
• Moderate-to-severe hematuria has been reported in 5% of patients

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 )
Hbo2 (Refractory haemorrhagic
cystitis, radiation therapy or
cyclophosphamide-induced)
diminishing oedema and
promoting neovascularization
100% oxygen at a 2 to 3
atm pressure for 90
minutes in 30 to 40
sessions
- 80% to 90%
(2.5yr)
5-year
complete
response rate
only 27%
claustrophobia (20%), otalgia
(17%), and, rarely, seizures

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

36. URETHRAL BLEEDING / urethrorrhagia
• Bleeding emanating from urethra at a point distal to bladder neck, occurring separate
from micturition
• Initial hematuria/ blood at urethral meatus in the absence of volitional micturition
• RGU and cystourethroscopy-mainstays for diagnosis
• In men, trauma to the urethral epithelium is most common cause
• Urethral caruncles
• Benign urethral lesions
• Arises from prolapse of distal posterior lip of urethra
• Most common in postmenopausal women
• Consequence of oestrogen deficiency
• Urethral diverticulum
• Classic presentation of dysuria, dyspareunia, and dribbling, intermittent episodes of
bleeding
• Urethral discharge may be noted on examination.

38. 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

40. • 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

41. • 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

42. Lateralizing Essential Hematuria and the 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