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National Pathology Group June 2003

National Pathology Group June 2003
Guideline for:
THE INVESTIGATION OF HAEMATURIA THE INVESTIGATION OF HAEMATURIA
Definition
Haematuria is defined as the excretion of intact or partially damaged erythrocytes
in the urine in quantities that exceed a population-derived threshold of normal i.e
>3 red blood cells per HPF of centrifuged urine
or
>8000 red blood cells per ml of uncentrifuged urine
Haematuria should be considered a symptom of serious disease until proved other-
wise.
Haematuria can present as:
Gross haematuria usually uroepithelial in origin.
Microscopic haematuria is defined as the excretion of more than 3 red blood
cells / HPF in the centrifuged sample or >8000 red blood cells per ml of uncen-
trifuged urine usually nephritic in origin
Positive dipstick false positive results may occur when the urine contains povi-
done or hypochlorite. The dipstick has false-negative rates of up to 18%, and it
is therefore prudent not to rely on the dipstick when specifically searching for
haematuria e.g. unexplained flank mass, urinary symptoms, oedema. In such
cases, urine for microscopic examination is always warranted.
Initial laboratory investigations
A clean-catch midstream urine specimen for urinalysis, including microscopy and culture, should
be obtained using aseptic technique to avoid contamination from the genitalia.
Microscopic examination of the urine is essential to confirm the diagnosis, but it is also necessary
to examine the red cells for dysmorphia, and urine for casts.
Microscopic differentiation of the RBCs into dysmorphic or isomorphic (normal) can assist in differ-
entiating between glomerular- and nonglomerular sources of bleeding and hence guide further
investigation. Automated flow cytometry (FBC machines) of urine is a more accurate method
than microscopy to differentiate glomerular from nonglomerular haematuria, based on the size of
the red blood cells. The urinary red cells in glomerular haematuria are smaller than normal (<70
fl; microcytic).
Once categorized, investigate the haematuria further according to the suspected site of origin
(glomerular vs nonglomerular).
Both glomerular- and nonglomerular haematuria patients should have the following baseline
blood tests:
FBC, ESR U&E, creatinine Protein profile
Cholesterol Calcium, phosphorus ALT
Alkaline phosphatase Uric acid Blood glucose
In glomerular haematuria (i.e. microcytic or dysmorphic red blood cells, heavy proteinuria, red-
cell casts), search for primary and secondary causes by using the history, physical examination,
and selected laboratory tests which include:
ANF, anti-DNA Hepatitis B surface antigen
ASO titre Complement components C3 and C4
Non-glomerular haematuria: Further urological investigation, including renal and bladder ultra-
sonography, IVP, excretory urography, and cystourethroscopy, if more than 3 RBCs/HPF are
found in at least 2 or 3 properly collected urine samples and the red blood cells are isomorphic
and normocytic, or if gross haematuria (>100 RBCs/HPF) is found on a single urinalysis.
Other studies include: CT scanning, Renal angiography, Ureterorenoscopy, Renal biopsy
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National Pathology Group June 2003
National Pathology Group June 2003
CAUSES
SPECIFIC LABORATORY TESTS
Glomerular haematuria

1 Primary
Renal biopsy
IgA nephropathy (Bergers disease)
Mesangial proliferative gn.
Membranoprofilerative gn.
Crescentic gn.
Focal gn.
Membranous gn.
Fibrillary gn.
Minimal change disease

2. Multisystem disease
Renal biopsy
Lupus nephritis ANF, anti-DNA, anti-ENA
Rheumatoid vasculitis
Rheumatoid factor
Wegeners granulomatosis
ANCA
Goodpastures syndrome

3. Infections

Postinfectious glomerulonephritis ASO titers and anti-DNaseB
Infective endocarditis Blood cultures
Bacterial pneumonia
Viral hepatitis Hepatitis A, B and C serology
HIV infection HIV antibodies
Malaria Malaria smears, antigen and QBC
Syphilis Syphilis serology
4. Hereditary disease
Alports syndrome
Fabrys disease
Thin basement membrane nephropa-

5. Other

Drug-induced nephropathy e.g.
NSAIDS
Aspirin
Captopril
Cephalosporins
Penicillins
Ciprofloxacin

Diabetic nephropathy
Malignant hypertension
Blood glucose
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National Pathology Group June 2003
National Pathology Group June 2003
CAUSES SPECIFIC LABORATORY TESTS
Nonglomerular haematuria
Renal calcul
Renal biopsy
Uroepithelial tumours esp.
Urine cytology
Renal cell carcinoma

Wilmstumour

Metastatic tumours

Bladder carcinoma Urine NMP-22 this involves the quantitative detec-
tion of a specific nuclear matrix protein. This assay of-
fers great potential for the early detection of recur-
rent bladder carcinoma; their role in the evaluation of
haematuria is still uncertain
Prostate carcinoma
PSA
Benign prostatic hypertrophy

Infection e.g.

Urinary tract infection
Urine MCS
Prostatitis

Schistosomiasis
Terminal urine collected between 11h00 and 15h00
for microscopy
Tuberculosis Early morning urine specimen for AFB + mycobacte-
rial culture
Pyelonephritis
Urine MCS
Metabolic disorders e.g.

Hypercalciuria
Serum calcium
Hyperuricosuria
Serum uric acid
Vascular

Renal infarction

Trauma

Coagulation disturbance

Warfarin use
Coagulation studies
Heparin therapy

Thrombocytopenia

Strenous exercise Asymptomatic haematuria resulting from strenous ex-
ercise has been well documented in association with
a variety of contact and noncontacts sports. Exer-
cise-induced haematuria is typically a benign, self-
limiting process that resolves within 72 hours of onset.
If the haematuria is present on repeat urinalysis after
72 hours of rest, further urological evaluation may be
indicated.
REFERENCES
1. Sutton J M. Evaluation of hematuria in adults. J AMA 1990; 263: 2475 - 80
2. Abuelo GJ . The diagnosis of hematuria. Arch Intern Med 1983; 143: 967 - 70