Mr Timothy Hargreave provides advice on a common clinical conundrum

HAEMATURIA (blood in the urine) may be visible (macroscopic) or microscopic. Visible haematuria is dramatic and most patients will not allow the matter to be ignored! All patients with macroscopic haematuria should be investigated.

In clinical and medico-legal practice it is usually microscopic haematuria that causes problems because for every person with macroscopic haematuria there are hundreds with lab or dipstick-positive microscopic haematuria.

Everyone has blood in the urine

The average normal person has about 1 million red blood cells in the urine each 24 hours which equates to about one red blood cell per high power field when the urine is examined under the microscope. An excess of red blood cells in the urine can occur with various pathological conditions of the kidney and bladder. One of the most common is urinary tract infection and thus microscopic haematuria is a relatively frequent occurrence in women because they are more prone to such infections. Potentially lifethreatening conditions such as bladder cancer can also cause macroscopic or microscopic haematuria. The diagnostic challenge is to distinguish those people with amounts of blood sufficient to require further investigation and not to miss serious and life-threatening conditions such as bladder cancer.

The most frequently used method to test for blood is the chemical dipstick. In general the threshold for dipstick testing is designed to show negative when there are very low (normal) numbers of red cells in the urine and positive if more than normal, but with any lab test which involves thresholds there are false positives and negatives. In the interests of safety the threshold for the dipstick test tends to err on the side of false positive results. This results in relatively large numbers of people having positive dipstick tests for blood in the urine who then go on to further investigations which all turn out to be normal.

To avoid massive over-investigation it is normally recommended that in the absence of any other urinary symptoms or indicators (see my red flags opposite) referral for specialist opinion or investigations (cystoscopy and ultrasound imaging of the kidneys) should be deferred until after at least two positive dipstick tests. A less selective policy would be prohibitively expensive and probably do more harm than good. Although cystoscopy is a low-risk procedure there are nevertheless some risks, such as introducing urinary infection (or very rarely urethral trauma), and these have to be considered when dealing with large numbers of people. Most instances of chemical haematuria are of no significance and it is this dilemma that is a recurring source of litigation.

Processing urine specimens

Ideally patients should be given clear written instructions or directed to an appropriate website (e.g. www.patient.co.uk/health/Midstream- Specimen-of-Urine-(MSU).htm). For those who are asked to provide a repeat sample following an initial positive test it is worthwhile re-emphasising collection instructions as people tend to take a lot more care for any repeat test. For detection of true positive blood it is best to collect a midstream sample taken during the first void after waking.

A common error which can result in litigation is the single positive test which is then forgotten, filed, ignored or simply written off as a false positive because of the lack of any symptoms. Another problem is failure of communication between health screening clinics, occupational health clinics and general practice so that results are not collated and nobody identifies that more than one urine test has been positive. It is always a good idea to advise the patient that there is a positive for blood urine test and that the test needs to be repeated and that the patient should chase the matter up if arrangements fail. Written advice to the patient is particularly helpful when different agencies are involved.

Red flags

There are a number of indicators which would lower my threshold for investigation or would indicate the need for a third urine test three to six months later in a situation where the first test is positive and the second test negative.

More than one positive for blood urine dipstick test or more than one positive for blood urine lab test. Further investigation is normally indicated in this situation.

Proteinuria and in particular casts (if microscopy has been performed) may indicate renal disease. To confirm proteinuria it is often appropriate to repeat the urine test taking particular care about urine collection, especially in women. Other indicators of possible renal disease include hypertension and raised blood urea or creatinine. There is a trap for the unwary in patients with indicators of renal disease and macroscopic haematuria as renal disease may co-exist with bladder pathology such as transitional cell carcinoma. The general rule is that all patients with macroscopic haematuria should have a cystoscopy and upper tract imaging by ultrasound. There has been litigation when a more advanced bladder cancer has been found after several years of medical treatment for renal impairment.

Ask about symptoms. With the exception of obvious urinary infection (e.g. frequency, dysuria and positive urine bacterial culture), any other symptoms such as dysuria, pain and tiredness should be a red flag. Debris or bits and pieces in the urine, particularly in an older person, should not be ignored.

Regard men with suspicion! Men are generally less prone to urinary infection than women and microscopic haematuria is less frequent. Older men may get urinary infection in association with prostate obstruction and residual urine but microscopic haematuria may also occur with prostate cancer.

Beware of smokers. There is a strong association between tobacco smoking (particularly cigarettes) and transitional cell cancer of the bladder. This is the fifth most common cancer in the UK (twice as common in men) and in its early stages can be treated through a cystoscope or by intravesical chemotherapy and without the need for major ablative surgery or radiotherapy. Missed bladder cancer despite two or more positive blood urine tests is a recurring source of avoidable litigation.

Consider occupation. Modern health and safety legislation restricting the use of carcinogenic chemicals in the rubber and chemical industries has made occupation a less important consideration. However, previous exposure to organic chemicals or mention in the patient history of past surveillance urine tests by an industrial occupational health service are indicators that the person may be at risk.

Recurrent urinary infection. Do not dismiss positive urine blood tests in the patient (often an elderly woman) with recurrent urinary infections, as squamous cell carcinoma of the bladder is associated with chronic urinary infection.

NICE guidelines

Current NICE guidelines (www.nice.org.uk/CG027) on referral for suspected urological cancer are more or less in accord with my own red flags although I take particular note of cigarette smoking. But the guidelines do not address the common situation where there is one positive test and then a repeat test 2-3 weeks later that is negative.

My bottom line advice is:

One positive test with no other indicators: wait 2 weeks and repeat test taking care to emphasise proper collection of the sample. If still positive refer for investigations. If negative discuss with patient and advise to come back if any symptoms or any change in urine colour OR arrange repeat urine test in 3-6 months; if 3-6 month repeat test negative no further action. Arranging the repeat test in 3-6 months has the advantage of not relying on the patient.

One positive test with a red flag indicator: the choice depends on the red flag indicator but is either to refer for investigation or repeat the urine test. If the repeat test is negative then I would organise a third repeat test in 3-6 months and of course advise the patient to come back if any symptoms.

Mr Timothy Hargreave MS FRCSEd FRCPEd FEB(Urol) is a senior fellow in the Department of Surgery at Edinburgh University and a former consultant urological surgeon at the Western General Hospital, Edinburgh

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