This document discusses the evaluation of hematuria. It defines hematuria as the presence of red blood cells in urine and classifies it as gross or microscopic based on visibility. Microscopic hematuria is defined as >3 RBCs/HPF on urine sediment analysis from two samples. The document outlines the workup for hematuria, including history, physical exam, urine analysis, investigations like cystoscopy based on findings, and distinguishing between glomerular and non-glomerular causes. Causes of hematuria include renal and urologic malignancies, infections, stones, vascular diseases, and medications. Morphology of RBCs on microscopy helps localize the source of bleeding.

1. EVALUATION OF HEMATURIA
Dr. Somendra Bansal
SMS Medical College, Jaipur

2. Hematuria:- Presence of RBC in urine
According to the amount of RBC in the urine,
hematuria can be classified as:
Gross Hematuria/Visible:- symptom
tea-colored, cola-colored, pink or even red
Microscopic/Non visible:- sign
normal colour with eyes

3.  Microscopic hematuria: >3 RBC/HPF on
microscopic evaluation of the urinary
sediment from two of three properly collected
midstream urine specimens
 If the patient is high-risk, one sample is
enough
American urological association guideline 2011

4. Glomerular hematuria
 Glomerular hematuria is suggested by the
presence of dysmorphic erythrocytes, RBC
casts and proteinuria
 IgA nephropathy (Berger disease) mc cause,
accounting for about 30% of cases

6. Nonglomerular hematuria
Renal cause:
 Malignancy
 Trauma
 Nephrolithiasis
 Papillary necrosis(DM/African-american secondary to
sickle cell disease/Analgesic abuse)
 Renal infarct
 Polycystic kidney Ds, Medullary sponge kidney Ds
 Vascular disease- (Renal artery embolism &
thrombosis, A-V fistula and renal vein thrombosis)
 Infection- (pyelonephritis, TB, CMV, EBV)

7. Non renal cause:
 Malignancy (bladder,prostate, ureter)
 Calculi
 BPH
 Infection (UTI/ GUTB)
 Endometriosis
 Instrumentation/ Trauma

8. Others:
 Hematologic: Coagulopathy, Sickle cell disease,
Thalassaemia
 Fictitious: vaginal bleed
 Strenuous exercise (marathon runner’s hematuria)
 Anticoagulants
 False hematuria: Food pigments, malingering, drugs
metabolites
Anticoagulation at normal therapeutic levels, however,
does not predispose patients to hematuria (campbell-
10 ed/89)

9. Mechanisms by which drugs cause Hematuria
Interstitial nephritis: Captopril
NSAIDs
Rifampin
Silver sulfadiazine
Penicillin
Papillary necrosis: Acetylsalicylic acid(aspirin)
NSAIDS
Hemorragic cystitis: Cyclophosphamide
Ifosfamide
Mitotane
Urolithiasis: Carbonic anhydrase inhibitor
Indinavir,Ritonavir
Triamterene

10. Hematuria of nephrologic origin
 Significant proteinuria
 Renal insufficiency
 Dysmorphic RBCs in the urine
 Predominance of red cell casts
 Elevated serum creatinine level

11. Hematuria of urologic origin
 Smoking history
 Occupational exposure to chemicals or dyes
 History of gross hematuria
 Age > 40 years
 Previous urologic disorder or disease
 History of irritative voiding symptoms
 History of recurrent urinary tract infection
despite appropriate use of antibiotics

12. Transient hematuria
 Transient microscopic hematuria is a
common problem in adults
 Fever, infection, trauma, and exercise are
potential causes
 Repeat an abnormal urinalysis in a few days
 Malignancy risk in older patients with
transient hematuria

13. Exercise-induced hematuria
 It typically occurs in long-distance runners (>10
km), is usually noted at the conclusion of the run,
and rapidly disappears with rest
 May be of renal or bladder origin
 Dysmorphic RBC suggesting a glomerular origin.
Exercise-induced hematuria may be the first sign
of underlying glomerular disease such as IgA
nephropathy
 Cystoscopy in patients with exercise-induced
hematuria of bladder origin frequently reveals
punctate hemorrhagic lesions in the bladder

14. Essential/Idiopathic hematuria
 Diagnosis of exclusion and can be made only
when no cause for hematuria is found after
exhaustive investigation

15. Evaluation of hematuria
 Hematuria of any degree should never be
ignored and, in adults, should be regarded as a
symptom of urologic malignancy until proved
otherwise and demands immediate urologic
examination
 MC cause of gross hematuria in a patient > 50
years - bladder cancer

16.  Older women and men who present with
hematuria and irritative voiding symptoms
may have cystitis secondary to infection arising
in a necrotic bladder tumor or, more
commonly, flat carcinoma in situ of the
bladder
 In a patient who presents with gross
hematuria, cystoscopy should be performed as
soon as possible, because frequently the
source of bleeding can be readily identified

17. History
1)Nature of hematuria:
 Gross or microscopic
 Intermittent/ continuous
 At what time during urination (beginning/
initial or end of stream/terminal or during
entire stream/total)
 Is the patient passing clots?
 If passing clots, specific shape

18. Timing of hematuria:
 Initial hematuria: distal to external
sphincter(urethra); least common and is usually
secondary to inflammation
 Total hematuria:(MC), bladder or upper urinary tracts
 Terminal hematuria: usually secondary to
inflammation in the area of the bladder neck or
prostatic urethra
It occurs at the end of micturition as the bladder
neck contracts,squeezing out the last amount of
urine

19. Presence of Clots:
 usually indicates a more significant degree of
hematuria
 probability of identifying significant urologic
pathology increases
Shape of Clots:
 amorphous - bladder or prostatic urethral origin
 vermiform (wormlike) - particularly if associated
with flank pain - hematuria from the upper
urinary tract

20. Associated symptoms:
2)Pain:
 Location (flank,groin,suprapubic,other), nature
 Hematuria, although frightening, is usually not
painful unless it is associated with inflammation
or obstruction.
 Patients with cystitis and secondary hematuria
may experience painful urinary irritative
symptoms
 Pain in association with hematuria usually results
from upper urinary tract hematuria with
obstruction of the ureters with clots
3)LUTS: (Dysuria, frequency, urgency)

21. 4) History of fever, facial puffiness, pedal edema
5) Recent URI/ sore throat
6) Medications (anticoagulants, analgesic, OCP)
7) Co-morbidity like TB, DM, HTN
8) Coagulation disorders & family h/o renal disease
9) Trauma
10) Strenuous exercise
11) Menstruation
12) Cyclic hematuria in women that is most prominent during
and shortly after menstruation, suggesting endometriosis of
the urinary tract
13) Travel or residence in areas endemic for Schistosoma
hematobium (Endemic hematuria)

22. Family history
 Hematuria
 Hearing loss
 HTN
 Stones
 Renal disease
 Dialysis or transplant
 Sickle cell trait
 Coagulopathy

23. Physical examination
 Vital sign: Pulse, BP, Temp
 Paleness, jaundice
 Edema (especially periorbital)
 Skin: Rashes, evidence of trauma, bruising
 Abdomen: for mass,tenderness(flank,
suprapubics), bruits
Costovertebral angle tenderness in afebrile
patient is suggestive of ureteral obstruction,
often secondary to stone disease,. When fever
and flank tenderness are both present diagnosis
of pyelonephritis should be entertained
 Careful inspection of external genitalia
 PR- Prostate

24. Cluesfromhistory that point towarda
specificdiagnosis
 Hematuria with urinary frequency, urgency and dysuria
bladder or lower urinary tract (UTI, Tuberculosis or Tumor)
if accompanied by high spiking fever, chill and loin pain:
pyelonephritis
 Hematuria with renal colic
renal stone, ureteric stone
if with dysuria, micturation pause or staining to void:
bladder or urethral stone
 Sterile pyuria with hematuria
occur with renal tuberculosis, analgesic nephropathy and
other interstitial diseases

25.  Symptoms of prostatic obstruction in older men such as
hesitancy and dribbling. The cellular proliferation in BPH is
associated with increased vascularity, and the new vessels can
be fragile
 A positive family history of renal disease give suspicion of
hereditary nephritis, polycystic kidney disease, or sickle cell ds
 A recent URI raise the possibility of either post infectious
glomerulonephritis or IgA nephropathy

26. Investigations
 Urine analysis (Dipstick/ urine microscopy)
 For those with history suggestive of infection and
associated pyuria, a urine culture and sensitivity
should be done to rule out infection
 After confirmation of erythrocytouria, the next step is
to differentiate between glomerular and
nonglomerular hematuria
Glomerular hematuria (presence of dysmorphic
RBC and RBC casts and usually associated with
proteinuria)
Nonglomerular hematuria - USG abdomen is next
step to detect any anatomical abnormality in the
urinary tract (e.g. stones, renal cysts, renal mass,
bladder tumor, prostatomegaly, hydronephrosis)

27.  CBC,RFT, blood sugar and coagulogram must be
done to rule out other causes and as a part of
workup for surgery if an abnormality is detected
on ultrasonography
 In absence of features of glomerular hematuria,
urinary tract infection and USG evidence of renal
mass, most patients would require
cystourethroscopy. Certain investigations are
suggested, before proceeding for the same-
1. Urine cytology for malignancy
2. Urine for AFB
3. Intravenous urography / CT urography

28. Glomerular causes: Renal biopsy
 A biopsy is not usually performed for isolated
glomerular hematuria (i.e., no proteinuria or renal
insufficiency) since there is no specific therapy for
these conditions, unless the patient is considering
becoming a kidney donor
 However, biopsy should be considered if there is
evidence of progressive disease as manifested by
an elevation in the plasma creatinine
concentration, increasing protein excretion, or
unexplained rise in blood pressure

29. Test Advantages Disadvantages
Intravenous pyelogram (IVP)
Excellent visualization of the
kidney, collecting system, and
ureter
May miss bladder lesions; can
cause nephrotoxicity,
idiosyncratic reactions (1/10,000)
Cystoscopy
Best way to examine the bladder,
which is not as well visualized by
IVP or ultrasound
Invasive, uncomfortable and
expensive
Ultrasound
If of good quality, as sensitive as
IVP for renal lesions, with less
morbidity and cost
Less sensitive than IVP for ureter
and bladder
Retrograde pyelography
The best test for examing the
ureters, can be combined with
cystoscopy
Invasive, not useful for examining
other parts of the urinary
collecting system
Urinary cytology
Sensitivity 67 percent, specificity
96 percent for uroepithelial cancer
Useful only for cancer, mainly of
the bladder
CT scan
Excellent for examining the renal
parenchyma
Expensive
Angiography
Useful for gross hematuria when
other tests have not revealed the
cause; the only good test for
vascular malformations
Invasive, expensive

31. AUA GUIDELINE ON ASYMPTOMATIC
MICROHEMATURIA JUrologyVol.188,2473-2481,December2012

32. Urine analysis
 Current standard of care for patients with
asymptomatic nonvisible hematuria is to undergo
urinalysis on at least two separate occasions,
 whereas those with symtomatic nonvisible
hematuria or visible hematuria are referred
immediately after one positive urinalysis and
exclusion of transient causes of hematuria and
UTI
Cowan NC. Nat.Rev.Urol.9,218-26(2012)

33.  Microscopic hematuria is detected by dipstick
method or microscopic examination of urinary
sediment
 Dipstick method to detect hematuria depends on
the ability of hemoglobin to oxidize a chromogen
indicator(peroxidase like activity of hemoglobin)
with the degree of the indicator color change
proportional to the degree of hematuria
 Dipsticks have a sensitivity of 95% and a
specificity of 75% and positive results should be
confirmed with a microscopic examination of the
urine

34.  Microscopic examination of urine is performed on
10 mL of a midstream, clean-catch specimen that
has been centrifuged for 10 minutes at 2000 rpm
 Supernatant is discarded and sediment is
resuspended and examined under high power
magnification (X400 power)
 Microhematuria is diagnosed in presence of more
than 3 RBCs per high power field in adults and 5
or more in children and in trauma cases

35.  A positive dipstick for blood in urine: hematuria,
hemoglobinuria or myoglobinuria and certain
antiseptic solutions (povidone-iodine)
 Microscopic examination of centrifuged urine
Erythrocytes present:-hematuria
Erythrocytes absent:-serum examination
Hemoglobinuria-supernatant pink
Myoglobinuria-serum clear

36. Causes of False-positive dipstick readings
 Contamination of urine specimen with menstrual
blood
 Dehydration-high specific gravity
 First morning voided specimen-high specific
gravity
 Exercise
 Semen is present in the urine after ejaculation
 An alkaline urine with a pH greater than 9 or
contamination with oxidizing agents used to clean
the perineum
 The presence of myoglobinuria

37. Causes of haem negative red urine
Medications Food dyes Metabolities
Doxorubicin
Beets (in selected
patients)
Bile pigments
Chloroquine Blackberries Homogentisic acid
Deferoxamine Food coloring Melanin
Ibuprofen Methemoglobin
Iron sorbitol Porphyrin
Nitrofurantoin Tyrosinosis
Phenazopyridine(Pyridiu
m)
Urates
Phenolphthalein
Rifampin

38. Extraglomerular Glomerular
Color (if macroscopic) Red or pink
Red, smoky brown, or
"Coca-Cola"
Clots May be present Absent
Proteinuria <500 mg/day May be >500 mg/day
RBC morphology Normal Dysmorphic
RBC casts Absent May be present

39.  Morphologic evaluation of erythrocytes in the
centrifuged urinary sediment also helps localise their
site of origin
Phase-contrast microscopy
to distinguish glomerular from post glomerular
bleeding
 Dysmorphic RBC- Glomerular disease
 Round shape (normal shape and size of RBC)-
Tubulointerstitial renal disease and urologic origin

40. Phase contrast Microscopy
Erythrocytes of uniform
character are classified as
isomorphic and suggest
hematuria of lower urinary
tract origin
Microscopic clots of clumped
erythrocytes in urine are also
suggestive of lower urinary
tract bleeding

41. Dysmorphic erythrocytes are
characterized by an irregular
outer cell membrane and
suggest hematuria of
glomerular origin
Red blood cell casts are also
associated with a glomerular
cause of hematuria

42. Cytology
Recommended:
 when risk factors for transitional cell carcinoma are
present
 as an adjunct to cystoscopic evaluation of the bladder, if
there is a question of irritative voiding symptoms
(especially in determination of carcinoma in situ)
Obtain urothelial cells which routinely exfoliate into the
urine:
 from a voided specimen
 from a bladder wash specimen in which bladder is
irrigated at time of cystoscopy or bladder
catheterization
 yield from “bladder wash”(barbotage) is higher than
that of a voided urine specimen

43. AUA Guideline JUrologyVol.188,2473-2481,December2012
 AMH is defined as three or greater RBCs per
high powered field on a properly collected
urinary specimen in the absence of an obvious
benign cause. 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

44.  The assessment of the AMH patient should
include a careful history, physical examination
and 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
Clinical Principle

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

46.  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

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

48.  MH that occurs in patients who are taking anti-
coagulants requires urologic evaluation and
nephrologic evaluation regardless of the type
or level of anti-coagulation therapy
Recommendation (Evidence Strength: Grade C)

49.  For the urologic evaluation of AMH, cystoscopy
should be performed on all patients aged 35 years
and older Recommendation (Evidence Strength: Grade C)
 In patients younger than age 35 years, cystoscopy
may be performed at the physician’s discretion
Option (Evidence Strength: Grade C)

50.  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), regardless of age
Clinical Principle

51.  The initial evaluation for AMH should include a
radiologic evaluation. Multi-phasic CTU
(without and with intravenous 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
Recommendation (Evidence Strength: Grade C)

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

53.  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, combining
MRI with retrograde pyelograms (RPGs)
provides alternative evaluation of the entire
upper tracts Expert Opinion

54.  For patients with relative or absolute
contraindications that preclude use of
multiphasic 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 US with RPGs provides alternative
evaluation of the entire upper tracts
Expert Opinion

55.  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)

56.  In patients with persistent MH 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)

57.  Blue light cystoscopy should NOT be used in
the evaluation of patients with AMH.
Recommendation (Evidence Strength: Grade C)

58.  If a patient with a history of persistent AMH
has two 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
Expert Opinion

59.  For persistent AMH after negative urologic
work-up, yearly urinalyses should be
conducted
Recommendation (Evidence Strength: Grade C)

60.  For persistent or recurrent AMH after initial
negative urologic work-up, repeat evaluation
within three to five years should be considered
Expert Opinion

61. THANKS