1. HAEMATURIA (Whistle-stop tour)
Sarah-jayne Pollock
GPST1
04/09/2019
1 in 5 adults with visible blood in the urine and 1 in 12 adults with non-visible blood in the urine are subsequently discovered to have bladder cancer
Around 19,100 people in England are diagnosed with bladder or kidney cancer each year.
Both cancers affect men and women, although they are more common in men.
Most people diagnosed with bladder and kidney cancers are over 50, although people of all ages can be affected.
Smokers have a much higher risk of these cancers. Other things that increase your risk of getting bladder or kidney cancer include:
being overweight or obese some jobs, because of exposure to certain chemicals other medical conditions, such as kidney failure a family history of cancer

2. Objectives
Definition
Causes
Assessment
Referral guidelines

3. Haematuria
Haematuria is the presence of red blood cells in the urine. It can either be:
Macroscopic
(Visible / gross haematuria )
Microscopic
(Non-visible / dipstick positive haematuria)
Haematuria itself is a symptom and therefore management involves finding and treating the cause
In many cases no cause is found but certain cases must be investigated

4. Location! Location! Location
Pyelonephritis
Glomerulonephritis
Lithiasis
Acute Cystitis
Prostate: Ca / BPH
Inherited diseases (SCD, Polycystic Kidney Disease)
Medications
Tumors
Injury
Exercise
[Beeturia]
Kidney: IgA Nephropathy, Thin Basement Membrane disease, Alports syndrome
Extraglomperular: Benign or malignant tumors, PCKD, SCD, Pyelonephritis, Stones, Renal papillary necrosis, Trauma
Ureters: Stones, tumor, stricture, infection, trauma
Bladder: Benign / malignant tumors, stones, infection, chronic irritation, trauma

5. Assessment History Examination Urinalysis Routine Bloods Investigate
Smoking; Occupation
Examination BP
Urinalysis
Routine Bloods
PCR
Investigate
USS KUB
CT KUB
Cystoscopy

6. Significant Haematuria
Any single episode of macroscopic haematuria
Any single episode of microscopic haematuria in the absence of a UTI or other transient cause
Persistent asymptomatic microscopic haematuria
2/3 dipstick positive cases of microscopic haematuria (> 5 rbc per high power field in 2/3 or greater consecutive centrifuged specimens at least 1 week apart)

7. When to Refer According to the BAUS website…
Your GP will arrange urgent referral to the Haematuria Clinic of your local urology unit if:
you are over the age of 45 years, and have visible blood in the urine in the absence of infection
the blood fails to clear following antibiotic treatment for urinary infection
you have non-visible bleeding but significant urinary symptoms
you have non-visible bleeding, and you are over the age of 60 years with a high white blood count on a blood sample or discomfort when you are passing urine
referral criteria from primary care (haematuria)
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if malignancy is suspected then patients may be referred without prior investigation (1)
first-line investigations that may be undertaken in primary care are indicated in the investigations of haematuria section of the system
Urological referral
urological referral for further investigation is indicated in the following patients
all patients with macroscopic haematuria of any age
some patients <40 yrs with cola-coloured urine and an inter-current (usually upper respiratory tract) infection will have an acute glomerulonephritis, and a nephrology referral may be considered more appropriate if clinically suspected
all patients with symptomatic non-visible haematuria (s-NVH) (any age).
all patients with asymptomatic (a-NVH) aged ≥40 yrs
NB - in young adults (<40 yrs) who presents with cola-coloured urine and an inter-current (usually upper respiratory tract) infection, nephrology referral may be considered more appropriate since they are more likely to have acute glomerulonephritis than urological disease (1)  
Nephrological referral
nephrological referral, is indicated for patients
who have had a urological cause excluded
have not met the referral criteria for a urological assessment
need for a nephrology referral in this situation depends on factors other than simply the presence of haematuria
nephrology referral is recommended if there is concurrent
evidence of declining GFR (by >10ml/min at any stage within the previous 5 years or by >5ml/min within the last 1 year)
stage 4 or 5 CKD (eGFR <30ml/min)
significant proteinuria (ACR ≥30mg/mmol or PCR ≥50mg/mmol)
isolated haematuria (i.e. in the absence of significant proteinuria) with hypertension in those aged <40
visible haematuria coinciding with intercurrent (usually upper respiratory tract) infection
in the event the above criteria are not met, haematuria itself (visible or non-visible) does not require nephrology referral. Such patients should however continue to be monitored in primary care (1).
The National Institute for Health and Clinical Excellence (NICE) Cancer Referral guidelines recommends urgent referral of the following patients (considering bladder and renal cancers):
refer people using a suspected cancer pathway referral (for an appointment within 2 weeks) for bladder cancer if they are:
aged 45 and over and have:
unexplained visible haematuria without urinary tract infection or
visible haematuria that persists or recurs after successful treatment of urinary tract infection, or
aged 60 and over and have unexplained non-visible haematuria and either dysuria or a raised white cell count on a blood test
note in the previous version of the guidance (4) NICE stated to "..in patients aged 50 years and older who are found to have unexplained microscopic haematuria, an urgent referral should be made" :
Reference:
(1) Renal Association and British Association of Urological Surgeons (2008). Joint Consensus Statement on the Initial Assessment of Haematuria
(2) National Institute for Health and Clinical Excellence (NICE) Referral guidelines for suspected cancer  
(3) The Renal Association (May 2006).UK CKD Guidelines
(4) National Institute for Health and Clinical Excellence (NICE) Referral guidelines for suspected cancer  

8. It is the diagnosis of bladder cancer where there have been major changes for UK Urological practice in this document. Previously any painless visible haematuria of any age was referred by the 2WW guidelines. However as the PPV of any haematuria was 0.99 for men < 45 years, 2WW referral is recommended only for people with visible haematuria age >45 without a UTI, or persisting/recurring despite treatment of a UTI. NICE have raised the age limit for 2WW non-visible haematuria to 60 years of age with one of the additional findings:  Dysuria (PPV 4.5)  Raised White cell count on blood testing (PPV 3.9) Asymptomatic non-visible haematuria has a PPV of 0.79% and 1.6% for patients aged years and >60 years respectively and no longer require urgent referral. (Previously, any patients over 50 years who were found to have unexplained microscopic haematuria – an urgent referral was suggested). They have recommended a non-urgent referral for patients >60 years with recurrent UTIs (without haematuria) due to PPV 0.5%. The guideline development group considered that this was a population in which cancer could be missed (despite the below threshold PPV) and thus a nonurgent referral has been suggested. Due to the rising of the age parameters in both visible and non-visible haematuria but with the addition of recurrent/persistent UTIs – NICE expect the exercise to be cost neutral or a small cost increase.

9. The renal cancer guidance mirrors that of the bladder cancer as above
The renal cancer guidance mirrors that of the bladder cancer as above. PPV for renal cancer for any haematuria increases with age. In men from it increases from 4.35% (45-54 years of age) to 11.21% (65-74 years) but the PPV for 85 years). Again the PPV for age 5% for renal cancer however they recommended referral for this cohort of patients to be directed to colorectal (PPV >10% for colorectal cancer). The finding of a clinical mass on examination should be managed by either a colorectal or gynaecological (ovarian) 2WW appointment rather than a urological referral. There has been no mention in this document of how to refer the incidental finding of an abdominal mass identified clinically or on imaging that is thought to be arising from the urinary tract.

10. There is little change in comparison to the 2005 document apart from the removal of PSA testing in men with lower back pain (due to PPV 0.13) and weight loss in the elderly – only a very small number of men with weight loss, without LUTs with a normal DRE have been found in the literature. They suggest investigation into myeloma in primary care in the first instance. There is no mention of an age cut-off for referral or need for a certain life expectancy.

11. Microscopic haematuria This clinical review highlights one of the big problems of microscopic haematuria – when is it clinically relevant? (BMJ 2009;338:a3021) Microscopic haematuria statistics 2.5–20% of the population may have microscopic haematuria but less than 1.5% of these have significant pathology. So some people with microscopic haematuria will have serious underlying pathology, but a significant proportion won't. We risk over-investigating this latter group, and perhaps doing them harm. In 2006 the National Institute for Health Research concluded that it was not possible to develop an evidence-based guideline for the investigation and management of patients with microscopic haematuria because there simply wasn't enough evidence. So expert consensus opinion is the best we have. This clinical review was keen to introduce two new terms – visible and non-visible haematuria – to replace micro- and macroscopic haematuria, but for now I'll stick to the terms we are all familiar with as I can't see the benefit of using the new terms.
Investigations (and see flow chart below) If symptomatic or persistent asymptomatic microscopic haematuria: Measure blood pressure Bloods: Cr and eGFR Assess for proteinuria: spot ACR or PCR is fine. This review considered that 'trace' of haematuria on dipstick should be considered negative, and only ≥ + should be considered positive because of the sensitivities of the test sticks. Haemolysed and non-haemolysed blood on dipstick should be treated in the same way. If asymptomatic then 2 out of 3 dipsticks should be positive before further investigation is warranted (≥ 1+ blood). Urine microscopy is rarely indicated in primary care – samples degrade too quickly to produce reliable results and may falsely reassure you. Proteinuria is a marker of glomerular damage, especially when present in large amounts (at low levels it may indicate tubular disease or dysfunction). The presence of proteinuria and haematuria makes the likelihood of glomerular disease more likely: referral to the renal team is indicated. Significant proteinuria is 0.5g/day on 24 hr collection or spot PCR ratio of ≥50mg/mmol or spot ACR of ≥ 30mg/mmol. Do antiplatelet agents or anticoagulants cause haematuria? In those on aspirin or warfarin with painless macroscopic haematuria, up to 25% have an underlying pathology (so 75% or more don't). In those on aspirin or warfarin, 10% have painless microscopic haematuria, which is in line with the normal population. Only 10% of these had an underlying pathology. The authors conclude that because rates of microscopic haematuria are similar to the population rates we should not attribute it to the drugs without first investigating other causes. Managing microscopic haematuria Suggested algorithm for investigating haematuria (from BMJ article referenced above and adapted from the British Association of Urological Surgeons and the Renal Association). The authors recommend referring all those with symptomatic microscopic haematuria, although most in general practice would not do this if a UTI was the most likely cause – however, it may be worth considering this option if haematuria persists after treatment for a UTI or if UTIs are recurrent (?underlying cause). NICE Suspected cancer referral guidelines (2015 NG12) recommend urgent referral on 2ww pathway patients: Aged ≥60y with unexplained non-visible haematuria and either dysuria or raised blood white cell count (bladder cancer).