hematuria clasificacion

8/16/2019 Hematuria Clasificacion

1/41074 British Journal of Nursing, 2014, Vol 23, No 20

Haematuria: classification,causes and investigations

It 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, 5–10%

of people with non-visible blood in urine and 20–25% 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 88–95% and if

diagnosed at a late stage, falls to 22–35%. 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

ClassificationBlood 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 dipstick-

positive 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 isdetected 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

2 hours of being voided (Siemens, 2010). People commonly

bring urine samples in a variety of containers—e.g. miniature

spirit bottles, jam jars etc—which 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 negativeresult (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-NVHRed 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

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

Northumbria Healthcare NHS Foundation Trust

Accepted for publication: September 2014

AbstractThe 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 5–10% 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

British Journal of Nursing.Downloaded from magonlinelibrary.com by 193.061.135.080 on January 13, 2015. For personal use only. No other uses without permission. . All rights rese



■ Benign prostatic hyperplasia

■ Glomerulonephritis (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%.

Haematuria in patients taking anticoagulants and antiplatelet medicationBlood in urine, either visible or non-visible, in people

taking anticoagulants (for example, warfarin) or antiplatelet

medication (such as aspirin), should be investigated inthe 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).

Assessment of haematuria 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 indicatea 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.

Physical examinationThere 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

prostate cancer

■ In women, vaginal examination to exclude gynaecological

causes of haematuria e.g. vaginal bleeding, prolapse or

urethral caruncle (benign tumour visible at the urethral

meatus).

Investigations

There are a number of investigations that should beundertaken 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.

Referral to haematuria clinicsBetween 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 40 years

with haematuria and persistent or recurrent urinary tractinfection and all people over 50 years with a-NVH should

be referred to a haematuria clinic for investigation within

2 weeks 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 50 years of age with a-NVH, no proteinuria

and normal serum creatinine should be referred to the

haematuria clinic for non-urgent investigation.

Referral to a nephrologistReferral to a nephrologist may be considered more

appropriate if acute glomerulonephr itis is clinically suspected,

i.e. some people under the age of 40 years 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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British Journal of Nursing, 2014, Vol 23, No 20 107

UROLOGY

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equivalent to PCR 50 mg/mmol or more, or urinary protein

excretion 0.5 g/24 hours or more) should also be referred to

a nephrologist (NICE, 2008).

InvestigationsPeople 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, toexclude upper tract pathology, a CT intravenous urography,

intravenous urogram (IVU) or a kidneys, ureters and bladder

(KUB) X-ray.

Flexible cystoscopyA 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 reducethe 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 31 days.

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).

IVUIVU 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.

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 only26% of small masses that measure 3 cm

(Silverman and Cohan, 2007).

KUB X-rayKUB 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 cytologyThe epithelial lining of the bladder sheds cells that are

voided in ur ine. 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 low-

grade 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 markersBladder 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).

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)




Risk factors for urological malignancy

Smoking history

It is estimated that cigarette smoking is the cause of bladdercancer 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).

Occupational risksIt is estimated that approximately 7-10% of bladder cancer

diagnoses in the UK are associated with occupational

exposures. Bladder cancer is therefore a recognised industrialdisease.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 historyCyclophosphamide 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 patient’s 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

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

2 years or more (Cancer Research, UK 2014).

Previous pelvic radiotherapy

People who have previously been treated with radiotherapyto the pelvic area e.g. for testicular, cervical or prostate cancer

have approximately twice the risk of developing bladder

cancer (Cancer Research, UK 2014).

Medical historyPeople 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).

ConclusionSeeing blood in urine is a worrying symptom for people and

it usually prompts them to urgently seek medical advice. NVHis 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 2 weeks, 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,

increasing their chance of being cured of their disease. BJN

Conflict of interest: none

British Association of Urological Surgeons (2008) Joint Consensus Statement on

the Initial Assessment of Haematuria. http://tinyurl.com/kes6owu (accessed 24September 2014)

Cancer Research UK (2011a) Information for GPs (online). http://tinyurl.com/ns9mvmj (accessed 24 September 2014)

Cancer Research UK (2011b) Early Diagnosis of Kidney and Bladder Cancers(online). http://tinyurl.com/ns9mvmj (accessed 24 September 2014)

Cancer Research UK (2014) Bladder Cancer Risk Factors. (online) http://tinyurl.com/qaj37wp (accessed 7 October 2014).

Edwards TJ, Dickinson AJ, Salvatore N, Gosling J, McGrath J (2006) Aprospective analysis of the diagnostic yield resulting from the attendance of4020 patients at a protocol-driven haematuria clinic.BJUI Int 97(2): 301-5

Kelly JD, Fawcett DP, Goldberg JC (2009) Assessment and management ofnon-visible haematuria in primary care. BMJ (online). http://tinyurl.com/muqng9s (accessed 24 September 2014). doi: 10.1136/bmj.a3021

Koss LG, Rana SH (2012) Koss’s Cytology of the Urinary Tract with HistopathologicCorrelations. Springer, New York

National Institute for Health and Care Excellence (2005) Referral Guidelinesfor Suspected Cancer. http://tinyurl.com/q3nrcyu (accessed 24 September2014)

National Institute for Health and Care Excellence (2008) Chronic kidneydisease. Early identification and management of chronic kidney disease inadults in primary and secondary care. http://tinyurl.com/qg3amfu (accessed24 September 2014)

Reynard J, Brewster S, Biers S (2013) Oxford Handbook of Urology. OxfordUniversity Press, Oxford

Rodgers M, Nixon J, Hempel S, Aho T, Kelly J, Neal D, et al (2006) Diagnostictests and algorithms used in the investigation of haematuria: systematicreviews and economic evaluation. Health Technol Assess 10(18): iii-iv, xi-259

Siemens (2010) Siemens Healthcare Diagnostics Reagent Strips for Urinalysis(Package Insert), Siemens, Erlangen

Silverman SG, Cohan RH (2007) CT Urography. An Atlas.Lipincott Williams &Wilkins, Philadelphia

The Free Dictionary (2007) Myoglobinuria (online). http://tinyurl.com/k4gz48k (accessed 24 September 2014)

Wadhwa N, Kumar S, Tiwari A (2012) Non-invasive urine based tests forthe detection of bladder cancer. J Clin Pathol 65(11): 970-5. doi: 10.1136/

jclinpath-2012-200812

Table 1. Possible causes of red-coloured urine

Intrinsic substances Foods Drugs

■ Bilirubin

■ Haemoglobin

■ Myoglobin

■ Porphyrins

■ Artificial food colourings

■ Beetroot

■ Blackberries

■ Blueberries

■ Fava beans

■ Paprika

■ Rhubarb

■ Adriamycin

■ Chloroquine

■ Desferoxamine

■ Levodopa

■ Methyldopa

■ Metronidazole

■ Nitrofurantoin

■ Phenolphthalein

■ Phenytoin

■ Phenazopyridine

■ Prochlorperazine

■ Quinine

■ Rifampin

■ Sulfonamides

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