II. Definition
- Significant Hematuria: 3 Red Blood Cells/HPF or more
III. Epidemiology
- Malignancy risk based on Hematuria type
- Microscopic Hematuria: 5% malignancy risk
- Gross Hematuria: 30-40% malignancy risk
- Malignancy risk increases over age 35-40 years old
- Age under 40 years with Hematuria
- Healthy men with Hematuria at one time: 39%
- Age over 40 years with Hematuria
- Bladder CancerIncidence: 2.5%
- Age under 40 years with Hematuria
IV. Risk factors: Urologic malignancy risks (suggestive of significant cause of Hematuria)
- Tobacco Abuse
- Occupational exposures (leather dye, Rubber, tire)
- Trichloroethylene
- Benzenes
- Aromatic amines
- Chemotherapy agents (e.g. Alkylating Agents)
- Gross Hematuria
- Age over 35 years
- Male gender
- Pelvic irradiation history
- Chronic indwelling foreign body
- Voiding symptoms suggestive of irritation
- Chronic Urinary Tract Infection history
- Analgesic overuse
V. Causes
VI. Exam
- Blood Pressure
- Men
- Genitourinary examination
- Rectal Exam for Prostate size and nodularity
- Women: Pelvic examination
- Urethral mass
- Diverticula
- Atrophic Vaginitis
- Uterine bleeding
VII. Labs: All Hematuria cases
- Renal Function tests
-
Urinalysis with microscopic exam
- See Microscopic Hematuria
- Inadequate sample (contaminated with vaginal contents)
- Squamous epithelial cells >5/hpf
- Signs of renal disease
- Glomerular disease
- Urine brown (Coca-Cola color)
- Microscopy
- Red Blood Cell Casts
- Dysmorphic Red Blood Cells
- Proteinuria
- Extraglomerular disease
- Clots of blood
- Glomerular disease
VIII. Labs: Other tests to consider
- Voided urine cytology
- No longer recommended for routine Hematuria evaluation
- Cystoscopy has higher Test Sensitivity than either urine cytology or Bladder Cancer detection markers
- Defer cytology and Bladder Cancer detection marker testing to Urology
- Protocol
- Obtain three serial first-morning 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
- No longer recommended for routine Hematuria evaluation
- Nephropathy or Glomerulonephritis evaluation
- Urine Protein to Creatinine Ratio
- Antinuclear Antibody
- ASO Titer
- Serum complement (C3, C4, C50)
- Prostate
-
Coagulation Factors
- INR (ProTime, PT)
- Partial Thromboplastin Time (PTT)
- Miscellaneous tests
- Collect 24 hour Urine Calcium
- Collect 24 hour Urine Uric Acid
- Urinalysis of "Three Glass Test" (listed for historical purposes)
IX. Diagnosis
-
Helical CT Urogram (preferred)
- See CT Urogram for details
- CT Abdomen and Pelvis with three phases of contrast
- Non-contrast stone evaluation
- Nephrogram
- Delayed phase of the lower tract
- Renal Ultrasound
- Defines anatomy
- Signs of glomerular disease and Renal Cysts
- CT Urogram is usually preferred over Ultrasound
- 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
X. Evaluation: Protocol
- Approach: General
- Consider non-urinary source (e.g. vagina, Rectum)
- Gross Hematuria should be thoroughly evaluated including urologic Consultation
- Confirm adequate sample
- See 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 Consultation regardless of protocol below
- Gross Hematuria
- Anticoagulant use with asymptomatic Microscopic Hematuria
- 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
- Protocol
- Evaluate and treat for secondary cause
- Urinary treat infection
- Exercise Hematuria (march Hematuria, e.g. distance runners)
- Menses
- Genitourinary infection (including sexually tramsmitted infection)
- Recent urologic procedure
- Trauma
- Hematologic causes (consider Coagulopathy)
- Repeat Urinalysis with microscopy at 6 weeks following treatment
- Positive: Go to Step 2
- Negative: No further evaluation required unless symptomatic
- Evaluate and treat for secondary cause
- Indications
- 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 Red Blood Cells or Red cell 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
- Indications: Nephropathy (IgA Nephropathy, Alport Syndrome, Benign familial Hematuria)
- Step 3: Evaluate for urologic malignancy with imaging
- CT Urogram (preferred) OR
- Alternative imaging modality
- Indications
- Low risk of urologic malignancy (see above)
- Contrast Media Allergy
- Poor Renal Function
- Radiation contraindication (e.g. young age)
- Modalities (less optimal)
- MR Urography or MRI Abdomen and Pelvis
- Renal Ultrasound
- Non-contrast CT Abdomen and Pelvis (Stone protocol)
- Retrograde pyelogram
- Indications
- Step 4: Urologic Evaluation
- Protocol
- Urology Consultation
- Cystoscopy
- Consider urine cytology (3 first morning voids)
- Obtain only if recommended by local urology consultants
- Positive findings on cystoscopy, imaging or labs
- Management per urology
- Negative evaluation
- Go to step 5 below
- Protocol
- 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%
XI. References
- Cohen (2003) N Engl J Med 348:2330-8 [PubMed]
- Davis (2012) J Urol 188(6): 2473-81 [PubMed]
- Grossfield (2001) Am Fam Physician 63(6):1145-54 [PubMed]
- Grossfield (1998) Urol Clin North Am 25:661-76 [PubMed]
- Sharp (2014) Am Fam Physician 90(8): 542-7 [PubMed]
- Sharp (2013) Am Fam Physician 88(11): 747-54 [PubMed]
- Sutton (1990) JAMA 263:2475-80 [PubMed]