The document provides guidelines for evaluating a patient presenting with hematuria. It begins with terminology and background on gross versus microscopic hematuria. Common causes are discussed including infection, stones, trauma, and tumors. The evaluation involves taking a thorough history, physical exam, urinalysis, and based on risk factors, further tests may include renal imaging, cystoscopy, or nephrology referral. The goal is to identify any underlying renal disease or urologic malignancy as the cause of the hematuria.

2. Evaluation
of the patient with
Hematuria
Meshari Alzahrani
Medical Intern – MBBS
AUA Member
29/1/2014

3. Introduction
Terminology
Basic Science
Gross Hematuria
Pseudohematuria
Microscopic Hematuria

4. Terminology
 Haematuria : blood in the urine.
– gross, or macroscopic, when there is sufficient blood
present to color the urine red or brown.
– microscopic when the urine is visually normal in color
but is found to contain blood on chemical analysis or
microscopic evaluation.
– asymptomatic microhematuria (AMH) is defined as:
3 or greater RBCs / HPF on a properly collected urinary
specimen in the absence of an obvious benign cause.
 HPF : high power field
– Normally between 0 – 3 RBCs are seem per HPF

5. Gross Haematuria
Urine microscopy showing RBCs

6. Basic Science
 RBCs may be excreted in the urine by normal
persons.
 It is not known precisely how these cells
reach the urinary tract.
 However, the normal excretion rate is :
0.5 to 2 million RBCs/24 hr, or <5 RBCs/hpf on
microscopic examination of a urine
specimen.

7.  It is difficult to localize the site of bleeding
by routine examination of the patient with
hematuria.
 However, certain findings may be very
helpful depend on size & shape of RBCs.
For example, casts form in the
lumina of renal tubules.
Therefore, the presence of RBCs
casts localizes the site of bleeding
to the renal parenchyma.

8. Hematuria
Size
Shape
Source
Glomerular*
Irregular
Small
Nephron
Non-glomerular
Uniform
Larger
Peripheral
*The reason that make Glomerular RBCs irregular & small cause it pass through
kidney chemicals & nephron that lead to change in shape & size as long as its pass through these jurney

9. Common cause of Haematuria







Infection of the urine.
Kidney and bladder stones .
Trauma to the urinary tract.
Bladder tumors.
Prostate tumors.
kidney tumors and other kidney diseases.
Blood disorders

10. Approach to Patient
with blood in urine
History taking
Physical examination
Differential Diagnosis
Investigation, Lab , Radiology

11. History Taking
 Personal :
–
–
Gender ( female, male)
Age ( older, younger)
 Chief Complaint : Blood in Urine +/- Associated symptoms
 Duration : Acute , Chronic .
 History of presenting illness :
–
–
Onset : Sudden , Progressive , transient, persistent, recurrent
Pattern: gross vs. microscopic, constant vs.
intermittent, glomerular vs. extraglomerular , painless vs.
painful

12.  Associated symptoms :
– Fever, back pain, dysuria, urgency, frequency (UTI)
– renal colic or previous nephrolithiasis (renal stone
disease)
– weight loss, especially with abdominal pain (RCC)
– weight loss with a significant smoking
history, analgesic abuse, or exposure to industrial
dyes (bladder carcinoma)
– Symptoms of prostatic obstruction in older men
such as hesitancy and dribbling (BPE)
– recent sore throat or skin
infection, edema, hypertension
(glomerulonephritis)

13. – recent back, abdominal, or urethral injury or vigorous exercise
(trauma)
– history of heart murmur with recent dental or genitourinary
manipulation (endocarditis)
– or a history of bleeding from other sites, a previous bleeding
disorder, or family history of a bleeding disorder (systemic
coagulopathy).
– Cyclic hematuria in women that is most prominent during and shortly
after menstruation, suggesting endometriosis of the urinary tract.
– Sterile pyuria with hematuria, which may occur with renal
tuberculosis, analgesic nephropathy and other interstitial diseases
– Loin pain-hematuria syndrome (LPHS): (rare) recurrent episodes of
severe unilateral or bilateral loin (flank) pain that were accompanied
by gross or microscopic hematuria, associated with use of OCPs

14.  Urine Color, pattern:
–
–
–
–
–
–
–
What color is your urine?
Are you taking rifampicin? Have you eaten beetroot
(Beeturia)?
Is it pure blood or mixed with urine?
Are there any clots? (lower urinary tract source)
Does it happen all the time when you pass water?
Is it near the beginning, end or during the entire urine
stream?
Post operative , recent urological surgery ?

15. rifampicin
beetroot

16.  Family History : A personal or family history of
hematuria with:
– deafness or ocular abnormalities with
hematuria (Alport's syndrome)
– hematuria with progressive chronic renal failure
(ADPKD)
– (sickle Cell Anemia) lead to papillary necrosis
and hematuria.
 Travel History to or Endemic area of:
– (Schistosoma haematobium) is a common cause
of hematuria in certain endemic areas

17. Antibiotics
Penicillins (esp. methicillin, ampicillin)
Cephalosporins
Sulfonamides
Rifampin
 Drug History : should be taken with
Isoniazid
NSIDs
special attention to :
Indomethacin
–Antibiotic : Rifampin ( orange urine)
Phenylbutazone
Fenoprofen
–analgesics (papillary necrosis)
Naproxen
–cyclophosphamide (hemorrhagic cystitis) Tolmetin
Mefenamic acid
– anticoagulants,
Diuretics
–drugs known to cause acute interstitial
Thiazides
Furosemide
nephritis
Triamterene
Miscellaneous
Phenytoin
Cimetidine
Allopurinol
Azathioprine
Drugs Associated with Acute Interstitial Nephritis.

18. Physical Examination
 Vital signs should be checked with special attention to PB ( HTN with RCC
& glomerulonephritis, ADPKD) and temperature (fever with UTI)
Genital examination :
possible sites of bleeding around the urethral meatus in both sexes
Look for Trauma “ Foley’s Catheter Removal while balloon still inflated”
For male , look for : BPH, prostatic cancer, do PR
For female , look for : GYN/OBS abnormalities (vaginal bleeding)
Inspection :
Rash, ecchymoses, or petechiae (coagulopathy)
Lens abnormalities and hearing loss (Alport's syndrome)
Edema , sore throat , (glomerulonephritis)
Palpation: renal colic flank pain radiate to groin (stone) , costovertebral
angle tenderness , abdominal tenderness, and abdominal masses (RCC)
Auscultation : Cardiac murmurs (endocarditis)

19. Alport syndrome :
Hereditary nephritis characterized
by glomerulonephritis , end stage kidney disease,
and hearing loss. Alport syndrome can also affect
the eyes (lenticonus).
The presence of blood in the urine (hematuria) is
almost always found in this condition.

20. Differential Diagnosis of Hematuria
 Acquired glomerular and tubulointerstitial renal
disease
– Primary
–
Secondary to systemic disease (pericarditis)
 Hereditary renal disease
– Alport's syndrome
–
Polycystic kidney disease
 Infection (Mycobacteria and Schistosoma)
 Papillary necrosis
– Sickle hemoglobin
–
Analgesic abuse

21. Differential Diagnosis of Hematuria
 Trauma
 Calculi
 Neoplasia
– Primary
–
Metastatic (uncommon)
 Coagulopathy
– Congenital
–
Acquired

22. Investigation : Lab
 RFT : Serum Creatinine
 Urinalysis with microscopic exam
– Inadequate sample (contaminated with vaginal contents)
• Squamous epithelial cells >5/hpf
– Signs of renal disease
• Glomerular disease
– Urine brown (Coca-Cola color)
– Microscopy
» RBCs casts
» Dysmorphic RBCs
– Proteinuria
• Extraglomerular disease
– Clots of blood

23.  Voided urine cytology:
– No longer recommended for routine Hematuria evaluation
• Cystoscopy has higher Test Sensitivity than either urine cytology or Bladder
Cancer detection markers
– Protocol
• Obtain three serial fresh specimens
• Evaluate for transitional cell cancer
– Bladder Cancer detection markers (no evidence for benefit over standard
cytology or cystoscopy)
•
•
•
•
Fluorescent in situ hybridization (FISH)
Nuclear matrix protein 22 Test
Bladder tumor antigen stat test
Urinary Bladder cancer antigen
 Nephropathy or Glomerulonephritis evaluation:
•
•
•
•
Urine Protein to Creatinine Ratio
Antinuclear Antibody
ASO Titer
Serum complement (C3, C4, C50) : ↓

24.  Prostate:
• Prostate Specific Antigen (PSA)
 Coagulation Factors:
• INR , prothrombin time (PT)
• Partial Thromboplastin Time (PTT)
 Miscellaneous tests:
• Collect 24 hour Urine Calcium, Urine Uric Acid
 Urinalysis of "Three Glass Test" :
• Glass 1: Initiation of urine stream
– Hematuria in Glass 1 only suggests Urethral source
• Glass 2: Midstream urine
– Hematuria in all glasses suggests Bladder or renal
• Glass 3: Termination of urine stream
– Hematuria in Glass 3 only suggests Prostate source

25. Investigation : Radiology
• Helical CT Urogram (preferred) http://www.ajronline.org/doi/full/10.2214/AJR.10.4198
American Journal of Roentgenology. 2010
• Renal US
– Defines anatomy
– Signs of glomerular disease , hydronephrosis, and renal cysts
– CT Urogram is usually preferred over US
• Intravenous Pyelogram
– Suspected Nephrolithiasis
• Cystoscopy
– Extraglomerular source of Hematuria
• MRI Urography
– Indicated where CT Urogram is contraindicated (e.g.
Pregnancy, Children)
– Identifies urothelial cancer, Nephrolithiasis and renal tumors

26. Evaluation
Protocol
General
1
2
3
4
5

27. General Approach
– Consider non-urinary source (e.g. vagina, Rectum)
– Gross Hematuria should be thoroughly evaluated including
urologic intervention
– Confirm adequate sample
• Microscopic Hematuria
• Squamous epithelial cells >5/hpf suggests vaginal contaminant
• Urine Dipstick alone is inadequate due to high false positive rate
– False positives occur with Hemoglobinuria, Myoglobinuria and alkalotic
urine (pH >9)
– False negatives occur with Vitamin C Supplementation
– Indications for Urologic intervention regardless of protocols
• Gross Hematuria
• Anticoagulant use with AMH
• Old Age with Painless Hematuria
General
1
2
3
4
5

28. Gross hematuria
 Gross hematuria is suspected because of the
presence of red or brown urine.
 The color change does not necessarily reflect the
degree of blood loss, since as little as 1 mL of blood
per liter of urine can induce a visible color change.
 Gross hematuria with passage of clots almost always
indicates a lower urinary tract source.
 The initial step in the evaluation of patients with red
urine is centrifugation of the specimen to see if the
red or brown color is in the urine sediment or the
urine supernatant.

29. Approach to the patient with red or brown urine

30. Causes of Asymptomatic
Gross Hematuria by Incidence
•
•
•
•
•
•
•
•
•
•
Acute Cystitis (23%)
Bladder Cancer (17%)
Benign Prostatic Hyperplasia (12%)
Nephrolithiasis (10%)
Benign essential Hematuria (10%)
Prostatitis (9%)
Renal cancer (6%)
Pyelonephritis (4%)
Prostate Cancer (3%)
Urethral stricture (2%)

31. Acute renal failure — Gross hematuria
• occurring in patients with underlying
glomerular disease has been associated with
the development of transient acute renal
failure.
• Renal biopsy shows distension of many renal
tubules by intratubular red cells and tubular
cell injury consistent with acute tubular
necrosis

32. Microscopic Hematuria
– Urinary tract source
• Urethra or Bladder
• Prostate
• Ureter or Kidney
– Non-Urinary tract source
• Vagina
• Anus or Rectum

33. Pseudohematuria
(non-Hematuria related Red Urine)






Rifampin
Myoglobinuria
Hemoglobinuria
Bilirubinuria
Phenothiazines
Porphyria
 Pyridium
 Phenytoin
 Pyridium
 Red diaper syndrome
 Phenolphthalein Laxatives
 Foods (Beets, Blackberries, Rhubarb)

34. Step 1:Initial evaluation of isolated Hematuria
 Indications:
– Urine RBC 3/HPF or more OR
– Urine RBC < 3/HPF on 2 samples
• Incidental Microscopic Hematuria followed with 3
urine samples at 6 week intervals
• No further evaluation if Hematuria found only on one
of 4 samples
General
1
2
3
4
5

35.  Protocol
– Evaluate and treat for secondary cause
•
•
•
•
•
•
•
Urinary treat infection
Exercise Hematuria (march Hematuria, e.g. distance runners)
Menses
Genitourinary infection (STD)
Recent urologic procedure
Trauma
Hematologic causes (consider coagulopathy)
– Repeat Urinalysis with microscopy at 6 weeks following
treatment
• Negative: No further evaluation required unless symptomatic
• Positive: Go to Step 2
General
1
2
3
4
5

36. Step 2: Evaluate for Renal cause
 Indications:
– Nephropathy (IgA Nephropathy, Alport Syndrome, Benign
familial Hematuria)
• Proteinuria (1+ or greater on dipstick)
• Serum Creatinine elevated
• Dysmorphic RBCs or RBCs casts
– Suggests glomerular cause
– No dysmorphic cells suggests interstitial cause
 Protocol :
– (if indicated above, otherwise continue to step 3)
• Serum Creatinine with calculated GFR (obtain regardless of
urine sediment)
• Urine Protein to Creatinine Ratio
• Nephrology Consultation
General
1
2
3
4
5

37. Step 3: Evaluate for urologic malignancy
with imaging
– CT Urogram (preferred) , OR
– Alternative imaging modality
• Indications
–
–
–
–
Low risk of urologic malignancy
Contrast Media Allergy
Poor Renal Function
Radiation contraindication (e.g. pregnancy )
• Modalities (less optimal)
–
–
–
–
General
MR Urography or MRI Abdomen and Pelvis
Renal US
Non-contrast CT Abdomen and Pelvis (Stone protocol)
Retrograde pyelogram
1
2
3
4
5

38. The most common risk factors for
urinary tract malignancy in AMH patients
 Age >35 years
 Smoking history in which the risk correlates with the extent of
exposure
 Occupational exposure to chemicals or dyes (benzenes or
aromatic amines), such as printers, painters, chemical plant
workers
 History of gross hematuria
 History of chronic cystitis or irritative voiding symptoms
 History of pelvic irradiation
 History of exposure to cyclophosphamide
 History of a chronic indwelling foreign body
 History of analgesic abuse, which is also associated with an
increased incidence of carcinoma of the kidney
The American Urological Association (AUA)

39. Transitional cell carcinoma (TCC)

40. A : IVP
B: (CT)
C: CT urography

41. Step 4: Urologic Evaluation
– Protocol
• Urology Consultation
• Cystoscopy: urethra , prostate & bladder
• Consider urine cytology (3 first morning voids)
– Positive findings on cystoscopy, imaging or labs
• Management per urology
– Negative evaluation
• Go to step 5
General
1
2
3
4
5

42. Step 5: Surveillance following negative
Hematuria evaluation
– Repeat Urinalysis annually for 2 years following
initial evaluation
– Positive Urinalysis on either of the 2 rechecks
• Repeat Urinalysis, imaging and cystoscopy within 3-5 years
– Negative Urinalysis on both of the rechecks
• No further testing required unless symptomatic
• Risk of future urologic malignancy <1%
General
1
2
3
4
5

43. Diagnosis, Evaluation, and
Follow-up of (AMH) in Adult
AUA guideline

44. A systematic review of the
literature using the
MEDLINE database
(search dates January 1980
– November 2011)

45.  Asymptomatic microhematuria (AMH) is
defined as: 3 or greater RBCs / HPF
on a properly collected urinary specimen in the
absence of an obvious benign cause.
1

46.  A positive dipstick does not define
AMH, and evaluation should be based solely
on findings from microscopic examination
of urinary sediment and not on a dipstick
reading.
 A positive dipstick reading merits
microscopic examination to confirm or
refute the diagnosis of AMH.
Expert Opinion

47.  The assessment of the AMH patient
should include a:
– careful history
– physical examination
– laboratory examination
to rule out benign causes of AMH such as
infection, menstruation, vigorous exercise, medical
renal disease, viral illness, trauma, or recent
urological procedures.
2
Clinical Principle

48.  Once benign causes have been ruled
out, the presence of AMH should prompt a
urologic evaluation
Recommendation (Evidence Strength Grade C)
3

49.  At the initial evaluation, an estimate of
renal function should be obtained (may
include calculated eGRF, creatinine, and BUN)
because intrinsic renal disease may have
implications for renal related risk during the
evaluation and management of patients
with AMH.
Clinical Principle
4

50.  The presence of dysmorphic
RBs, proteinuria, cellular casts, and/or renal
insufficiency, or any other clinical indicator
suspicious for renal parenchymal disease
warrants concurrent nephrologic workup
but does not preclude the need for urologic
evaluation.
Recommendation (Evidence Strength Grade C)
5

51.  Microhematuria that occurs in patients who
are taking anti-coagulants requires urologic
evaluation and nephrologic evaluation
regardless of the type or level of anticoagulation therapy.
Recommendation (Evidence Strength Grade C)
6

52.  For the urologic evaluation of asymptomatic
microhematuria, a cystoscopy should be
performed on all patients aged 35 years and
older.
Recommendation (Evidence Strength Grade C)
7

53.  In patients younger than age 35
years, cystoscopy may be performed at the
physician's discretion.
Option (Evidence Strength Grade C)
8

54.  Regardless of age, A cystoscopy should be
performed on all patients who present with
risk factors for urinary tract malignancies
(e.g., irritative voiding symptoms, current or past tobacco
use, chemical exposures)
Clinical Principle
9

55.  The initial evaluation for AMH should include a
radiologic evaluation:
• Multi-phasic computed tomography (CT)
• Urography (without and with intravenous (IV) contrast)
including sufficient phases to evaluate the renal
parenchyma to rule out a renal mass and an
excretory phase to evaluate the urothelium of
the upper tracts, is the imaging procedure of
choice because it has the highest sensitivity and
specificity for imaging the upper tracts.
10
Recommendation (Evidence Strength Grade C)

56.  For patients with relative or absolute
contraindications that preclude use of multiphasic CT (such as renal
insufficiency, contrast allergy, pregnancy):
magnetic resonance urography (MRU) (without/with
IV contrast) is an acceptable alternative imaging
approach
Option (Evidence Strength Grade C)
11

57.  For patients with relative or absolute
contraindications that preclude use of
multiphase CT (such as renal
insufficiency, contrast allergy, pregnancy)
where collecting system detail is deemed
imperative:
(MRI) with retrograde pyelograms (RPGs)
provides alternative evaluation of the entire
upper tracts
Expert Opinion
12

58.  For patients with relative or absolute
contraindications that preclude use of
multiphase CT (such as renal
insufficiency, contrast allergy) and MRI
(presence of metal in the body) where
collecting system detail is deemed imperative:
 combining non-contrast CT or renal ultrasound
(US) with retrograde pyelograms (RPGs)
provides alternative evaluation of the entire
upper tracts.
13
Expert Opinion

59.  The use of urine cytology and urine markers
(NMP22, BTA-stat, and UroVysion FISH):
is NOT recommended as a part of the routine
evaluation of the AMH patient.
Recommendation (Evidence Strength Grade C)
14

60.  In patients with persistent microhematuria
following a negative work up or those with
other risk factors for carcinoma in situ (e.g.,
irritative voiding symptoms, current or past tobacco use,
chemical exposures):
cytology may be useful.
Option (Evidence Strength Grade C)
15

61.  Blue light cystoscopy :
should not be used in the evaluation of
patients with SMH.
(Evidence Strength Grade C)
16

62.  If a patient with a history of persistent AMH
has 2 consecutive negative annual
urinalyses (one per year for two years from the time of
initial evaluation or beyond):
then No further urinalyses for the purpose of
evaluation of AMH are necessary.
17
Expert Opinion

63.  For persistent AMH after negative urologic
work up:
Yearly urinalyses should be conducted.
Recommendation (Evidence Strength Grade C)
18

64.  For persistent or recurrent AMH after initial
negative urologic work-up:
Repeat evaluation within 3-5 years should be
considered.
Expert Opinion
19

66. References
• AUA
http://www.auanet.org/education/asymptom
atic-microhematuria.cfm#9
• http://www.fpnotebook.com/
• http://www.ncbi.nlm.nih.gov/books/NBK294/
• smith’s General Urology , edi17
• Etiology and evaluation of hematuria in
adults : Up To Date 2014

67. Thanks
29/1/2014
Meshari Alqoopisi