Haematuria: classification,

causes and investigations

Pauline Bagnall
Classification
The majority of patients who attend haematuria clinics for
investigation of blood in their urine will be found to have either no
cause or a benign cause. Between 20% and 25% of people with visible
blood in their urine and 510% of people with non-visible blood in
their urine will be diagnosed with a urological malignancy, i.e. bladder,
kidney or prostate cancer. Haematuria is therefore a significant
symptom that should be investigated promptly and thoroughly to
exclude cancer as quickly as possible. This article gives an overview
of the causes of haematuria and the investigations that patients will
undergo when referred to a haematuria clinic.
Key words: Haematuria Early detection of cancer
Prostate-specific antigen Urinary tract infections

t can be alarming for a person to see blood in

their urine and this often prompts them to seek
early medical advice, with many people attending
emergency care departments. Approximately 20% of
people diagnosed with bladder or kidney cancer each year
present as emergencies (Cancer Research UK, 2011a).
Although blood in urine can be from any site in the
urinary tract and can be a symptom of benign disease, 510%
of people with non-visible blood in urine and 2025% of
people with visible blood in urine will be diagnosed with a
urological malignancy (Reynard et al, 2013).
As over 80% of people diagnosed with bladder cancer and
over 50% of people diagnosed with kidney cancer present
with blood in their urine, a urological malignancy should be
excluded as soon as possible (Cancer Research UK, 2011a).
Early diagnosis of cancer results in improved survival rates.
If kidney and bladder cancers are diagnosed at the earliest
stage, the 1-year survival rate is as high as 8895% and if
diagnosed at a late stage, falls to 2235%. It is estimated that
approximately 1000 deaths from kidney and bladder cancers
could be avoided each year in the UK, if 5-year survival rates
matched the best in Europe (Cancer Research UK, 2011b).

Pauline Bagnall, Uro-oncology nurse specialist, Urology Department,

Northumbria Healthcare NHS Foundation Trust
Accepted for publication: September 2014

1074

Blood in urine is classified as either visible haematuria

(VH) or non-visible haematuria (NVH) (British Association
of Urological Surgeons (BAUS), 2008). VH, also called
macroscopic or gross haematuria, describes urine that is pink
or red in colour.
NVH is also called microscopic haematuria or dipstickpositive haematuria. It is sub-classified into symptomatic
NVH (s-NVH) if the patient also has lower urinary tract
symptoms, e.g. urinary frequency, urgency, or dysuria. If it is
detected incidentally during screening of patients who have
no urinary symptoms, it is sub-classified into asymptomatic
NVH (a-NVH).
A urine dipstick test is considered sufficient for the diagnosis
of NVH (BAUS, 2008). The urine should be collected in a
clean dry container and dipstick testing performed within
2hours of being voided (Siemens, 2010). People commonly
bring urine samples in a variety of containerse.g. miniature
spirit bottles, jam jars etcwhich can reduce the accuracy of
the dipstick result.
A urine dipstick test is considered positive if there is 1+
or above present, whether the result is haemolysed (broken
down red blood cells) or non-haemolysed (intact red blood
cells). Positivity for a trace of blood is considered a negative
result (BAUS, 2008). Significant haematuria is classified as
any single episode of VH, s-NVH or a-NVH on two out of
three dipstick tests.

Incidence of a-NVH
Red blood cells can be found in the urine of healthy people.
Approximately 70% of all people investigated for a-NVH
have no abnormality found. UK screening studies suggest
that the incidence of a-NVH in the adult male population
is around 2.5%, rising with age to up to 22% in men over
60 years (Rodgers et al, 2006).

Possible causes of haematuria

There are a number of possible causes of haematuria which
include:
Prostate cancer
Renal, ureteric or bladder calculi
Bladder cancer
Renal cancer
Ureteric cancer
Prostate cancer
Urinary tract infection; bacterial, mycobacterial (i.e.
tuberculosis) or parasitic (e.g. schistosomiasis)
Inflammation, e.g. intersitial cystitis

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Abstract

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prostatic hyperplasia
(urine may resemble cola in colour
when acute)
Trauma, e.g. traumatic urethral catheterisation or pelvic
fracture
Endometriosis
Exercise induced
Factitious (added by patient or carer). (Rodgers et al, 2006)
Edwards et al (2006) found that 7.9% of the 4020 people
referred to their protocol-led haematuria clinic over a 5-year
period, were found to have a benign cause, of which the
majority had stone disease. A urological malignancy was
diagnosed in 4.8% and for remaining patients results were
normal. Prevalence of malignant disease was 12.1%, in VH
18.9% and for NVH 4.8%.
Glomerulonephritis

Investigations

Blood in urine, either visible or non-visible, in people

taking anticoagulants (for example, warfarin) or antiplatelet
medication (such as aspirin), should be investigated in
the same way as in people not taking these medications.
Research has shown that up to 25% of people with VH and
10% of people with NVH taking these medications had
an underlying abnormality, including bladder cancer. The
incidence of NVH in anticoagulated people is similar to
non-anticoagulated people, and therefore cannot be blamed
entirely on these medications (Kelly et al, 2009).

There are a number of investigations that should be

undertaken when haematuria is present:
Urine culture to exclude a urinary tract infection. Once
any urine infection has been treated the urine should be
dipstick tested to ensure that the haematuria has resolved.
This is because people can present with a urine infection
as the first symptom of significant urinary tract pathology
Plasma creatinine/eGFR (estimated glomerular filtration
rate) to assess renal function
Prostate-specific antigen (PSA) should be offered after
counselling to male patients (once urinary tract infection
has been excluded) (National Institute for Health and Care
Excellence (NICE), 2005). Raised PSA would prompt
further investigation to exclude prostate cancer.
In addition people who have a-NVH should also have:
Blood pressure recorded
Proteinuria measured on a random urine sample. Send
urine to the laboratory for protein: creatinine ratio (PCR)
or albumin:creatinine ratio (ACR) on a random sample
(according to local practice). Raised blood pressure and
proteinuria may indicate glomerelonephtitis proteinuria.

Assessment of haematuria

Referral to haematuria clinics

Clinical history can identify possible causes and help to rule

out possible benign reasons for haematuria. The following
should be considered when assessing the condition:
At what point during voiding does blood appear? Blood at
the beginning of the stream, for example, would indicate
a prostatic or urethral cause, whereas blood on the toilet
tissue in females could have a gynaecological cause
Symptoms, e.g. pain, fever, urinary frequency urgency, that
could indicate a urinary tract infection or possible renal
calculi
Presence of clots; this would be conclusive of visible blood
in urine (red urine with clots in is haematuria as opposed
to coloured by other causes, and occasionally patients
describe having passed clots only without discolouration
of their urine)
Recent vigorous exercise, in particular running
Diet/foods that could discolour urine, e.g. beetroot (Table 1)
Medications that could discolour urine, for example,
prochlorperazine (Table 1)
Identification of risk factors for urological malignancy, e.g.
smoking history.

Between 20% and 25% of people with VH and 5-10%

of people with NVH will be found to have a urological
malignancy (Reynard et al 2013), therefore, all people with a
single episode of VH, s-NVH, all people aged over 40years
with haematuria and persistent or recurrent urinary tract
infection and all people over 50 years with a-NVH should
be referred to a haematuria clinic for investigation within
2weeks as instructed in the NICE (2005) guidelines.
People who have haematuria are often very anxious, not
only about what might be the cause of their haematuria but
also about the tests they will need to have. The 2-week wait
guideline ensures that people who have symptoms that may
be caused by cancer are seen within 14 days. Cancer must
then be diagnosed or excluded within 31 days and if it is
diagnosed, the patient should be treated within 62 days of
referral (NICE, 2005).
People under 50years of age with a-NVH, no proteinuria
and normal serum creatinine should be referred to the
haematuria clinic for non-urgent investigation.

Haematuria in patients taking anticoagulants

and antiplatelet medication

Physical examination
There are a number of different physical examinations that
can be conducted in order to assess for haematuria:
Examination of abdomen to exclude e.g. renal pain,
tenderness or masses
In men, rectal examination of the prostate to identify
any abnormality suggestive of benign enlargement or

1076

prostate cancer
women, vaginal examination to exclude gynaecological
causes of haematuria e.g. vaginal bleeding, prolapse or
urethral caruncle (benign tumour visible at the urethral
meatus).

In

Referral to a nephrologist
Referral to a nephrologist may be considered more
appropriate if acute glomerulonephritis is clinically suspected,
i.e. some people under the age of 40years who have a-NVH
with cola-coloured urine and an inter-current (usually upper
respiratory tract) infection (BAUS, 2008). Raised serum
creatinine and/or hypertension or proteinuria may indicate
renal disease, therefore, people with persistent a-NVH and
proteinuria (ACR 30 mg/mmol or more, approximately

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UROLOGY
equivalent to PCR 50mg/mmol or more, or urinary protein
excretion 0.5g/24hours or more) should also be referred to
a nephrologist (NICE, 2008).

Box 1. Terminology
Haematuria: blood in urine
Visible haematuria (VH): urine that is pink or red in colour
Non-visible haematuria (NVH): blood in urine which is
found on dipstick testing or microscopically
Symptomatic non-visible haematuria (s-NVH)
Asymptomatic non-visible haematuria (a-NVH)
Significant haematuria: 1+ or greater on two out of three
dipstick tests
Myoglobin: an oxygen-storing pigment found in muscle
tissue
Myoglobinuria (i.e. myoglobin in urine) is evidence of
severe muscle degeneration or injury, physical trauma, or
electrical injury (The Free Dictionary, 2007)

Investigations
People referred to a haematuria clinic for further investigation
will usually have a flexible cystoscopy to exclude bladder
and urethral pathology and a renal ultrasound scan, to
exclude upper tract pathology, a CT intravenous urography,
intravenous urogram (IVU) or a kidneys, ureters and bladder
(KUB) X-ray.

Flexible cystoscopy
A flexible cystoscope is a fine fibre optic tube that is inserted
into the bladder through the urethra to examine the bladder
urothelium, ureteric orifices and urethra. If the image is
transmitted to a monitor, the person performing the procedure
can show the patient and explain their results to them either
during or at the end of the procedure. A local anaesthetic
lubricant gel containing lidocaine and chlorhexidine is
inserted into the urethra to minimise discomfort and reduce
the risk of causing trauma and a urinary tract infection. The
risk of urinary tract infection is approximately 5% following
cystoscopy (Rodgers et al, 2006).
It may be possible for patients who do not wish to undergo
flexible cystoscopy under local anaesthetic to have the
procedure performed under sedation or general anaesthetic,
according to local policy.
It is possible to biopsy abnormal areas via a flexible
cystoscope. However, these biopsies will not be sufficient to
accurately stage cancer. Biopsies therefore, are not usually
performed if cancer is suspected, or even if a urothelial
malignancy is diagnosed and the patient will be asked to
return to have a cystoscopy and biopsies of any abnormal
areas, or transurethral resection of the bladder tumour
(TURBT) under general anaesthetic within 31days.
Flexible cystoscopy may be omitted if radiological
investigations conclusively demonstrate the presence of a
bladder tumour, in which case TURBT will be performed.

CT intravenous urography (IVU)

CT IVU provides an assessment of all of the major
urological structures except for the prostate and urethra and
is becoming the standard X-ray procedure for radiological
investigation of VH replacing IVU because of its increased
diagnostic accuracy. It can identify 80% of upper tract cancers
and 60% of bladder cancers and rarely gives false positive
results (Silverman and Cohan, 2007).

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IVU
IVU has for many years been the gold standard radiological
procedure for investigation of haematuria, able to identify
bladder and renal masses and renal calculi. However, it is unable
to differentiate between solid or cystic masses and is poor at
identifying small renal masses (Silverman and Cohan, 2007).
The procedure involves an injection of intravenous contrast and
several X-rays being taken as the contrast is eliminated by the
kidneys. A compression band may be fastened tightly around
the patients waist to improve visualisation of the kidneys.

British Journal of Nursing, 2014, Vol 23, No 20 

Renal ultrasound scan (USS)

USS is able to identify bladder and renal tumours and renal
calculi. It can also differentiate between renal cysts and renal
cancers. It is not, however, as sensitive as CT, identifying only
26% of small masses that measure <1 cm, 60% of masses
measuring 23 cm and 85% of masses measuring >3 cm
(Silverman and Cohan, 2007).

KUB X-ray
KUB is a plain X-ray of the kidneys, ureters and bladder and
may be used with USS in younger patients or for patients
who have contraindications to radiological contrast media,
(e.g. allergy or renal failure) to exclude renal calculi as the
cause of NVH. However, approximately 15% of renal calculi
are not radiopaque, and phleboliths (deposits of calcium in
blood vessels) may cause false-positive diagnosis of renal
calculi which then requires further investigation.

Urine cytology
The epithelial lining of the bladder sheds cells that are
voided in urine. These cells are centrifuged from the urine
and examined microscopically to identify abnormal cells.
Ideally the second void of the day should be collected
in a clean container and sent to the laboratory promptly.
Degeneration of cells means an early morning sample of
urine is unsuitable for cytological examination (Koss, 2012).
Urine cytology is not sensitive enough to diagnose lowgrade urothelial tumours and false positive results can be
found in people with benign conditions including urinary
calculi, chronic infection and inflammation, and in people
who have received radiotherapy or chemotherapy (Wadhwa
et al, 2012).

Voided markers
Bladder cancer cells release higher levels of nuclear matrix
protein (NMP22) than normal cells. Voided urine can be
tested for NMP22 at the haematuria clinic and the result be
available in 30 minutes, meaning patients can be informed at
the same time as their cystoscopy result. Like urine cytology,
false-positive results can also be found in people who have
a urine infection, renal calculi, haematuria, etc (Wadhwa et
al, 2012).

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Table 1. Possible causes of red-coloured urine

Intrinsic substances

Foods

Drugs
food colourings

Bilirubin

Artificial

Haemoglobin

Beetroot

Chloroquine

Myoglobin

Blackberries

Desferoxamine

Porphyrins

Blueberries

Levodopa

Previous pelvic radiotherapy

Fava

Methyldopa

People who have previously been treated with radiotherapy

to the pelvic area e.g. for testicular, cervical or prostate cancer
have approximately twice the risk of developing bladder
cancer (Cancer Research, UK 2014).

beans
Paprika
Rhubarb

Adriamycin

associated with people being at increased risk of developing

bladder cancer. Diabetics who have taken piogilitazone for
1-2 years have a 34% increased risk of developing bladder
cancer and the risk is doubles when people have taken it for
2years or more (Cancer Research, UK 2014).

Metronidazole
Nitrofurantoin
Phenolphthalein
Phenytoin
Phenazopyridine

Medical history

Prochlorperazine

People who are paraplegic have an increased risk of squamous

cell bladder cancer. This is likely to be because of their
increased risk of urinary tract infections and renal calculi
(Cancer Research UK, 2014).

Rifampin
Sulfonamides

Risk factors for urological malignancy

Smoking history
It is estimated that cigarette smoking is the cause of bladder
cancer in 38% of men and 34% of women diagnosed (Cancer
Research UK, 2014). Current smokers have two to three
times the risk of people who have never smoked with the risk
increasing with the number of years people have smoked and
the number of cigarettes smoked each day.
Smoking cessation reduces the risk, but the risk of
developing bladder cancer remains higher in people who
have quit smoking than in people who have not smoked for
more than 20 years. (Cancer Research UK, 2014).

Seeing blood in urine is a worrying symptom for people and

it usually prompts them to urgently seek medical advice. NVH
is often identified during health screening or investigation of
unrelated symptoms. Both symptoms require further
investigation to exclude transient causes, e.g. urine infection.
People with significant haematuria should be referred to a
haematuria clinic for investigation within 2weeks, if they fulfil
the criteria to exclude a urological cancer. This action will
ensure that people who are found to have cancer as the cause
of their haematuria will be diagnosed and treated early,
BJN
increasing their chance of being cured of their disease.

Occupational risks

Conflict of interest: none

It is estimated that approximately 7-10% of bladder cancer

diagnoses in the UK are associated with occupational
exposures. Bladder cancer is therefore a recognised industrial
disease.People who work in occupations that are at increased
risk of developing bladder cancer include painters, people
who are highly exposed to diesel fumes or polycyclic
aromatic hydrocarbons (PAH), a by-product of combustion
processes and people who work with or have worked with
aniline dyes (Cancer Research UK, 2014).

Medication history
Cyclophosphamide and pioglitozone are drugs that are

KEY POINTS
n Blood in urine is classified as either visible haematuria (VH) or non-visible
haematuria (NVH)
n Looking at a patients clinical history can identify possible causes and guide
apppropriate referral and investigation
n Assessment includes a combination of flexible cytoscopy and radiological
investigations
n Haematuria should be investigated promptly to aid early diagnosis of cancer

1078

Conclusion



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Quinine

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