Determining the amount and source of haematuria are two issues to address during investigation. A thorough history and examination should exclude a UTI, trauma, contamination from menstruation, and temporary causes; medications and physiological causes such as exercise, prosthetic heart valves and pregnancy (Urology, 2013) (Thomas, et al., 2007), as well as identifying risk factors for disease (Rodgers, et al., 2006) such as recurrent UTIs, other symptoms, family history, smoking, chemical exposure such as benzenes, previous haematuria and analgesia overuse (Grossfeld, et al., 2001). Examination of macroscopic haematuria must include assessment of vital signs to avoid haemodynamic instability; pallor; oedema; cachexia; tenderness in the flanks and suprapubic areas; prostatic assessment and lymph nodes.
Obtaining uncontaminated mid-stream urine (MSU) is required to test the urine. Various methods of urinalysis can be performed, most routine of which is dipstick analysis. Microscopic haematuria can be detected by urine dipstick, with confidence that presence of blood in the urine will cause a change on the dipstick; however a negative test cannot rule out haematuria (Rodgers, et al., 2006). A positive dipstick result cannot differentiate between types of haematuria such as blood or free haemoglobin. False positives are possible in haemoglobinurea, myglobinurea, beetroot, porphyria and some drugs (Longmore, et al., 2008). Dipsticks are so sensitive they may yield false positives in normal individuals (Kumar & Clark, 2005). Dipsticks cannot distinguish between causes or sites of origin of blood (Figure 1) (Kumar & Clark, 2005) and are one-off tests so may miss patients with pathologies such as malignancy, where haematuria is not always present (Rodgers, et al., 2006). False negatives can occur with high urinary levels of ascorbic acid (Tomson & Porter, 2002)Further investigation is often necessary.
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Urine MC&S, FBC, ESR, CRP, clotting and Us&Es all help narrow down possible diagnoses and causes of haematuria (Longmore, et al., 2008). Microscopy urinalysis requires a fresh sample; stored urine samples may undergo degradation and cause lysis of RBCs, potentially altering microscopy findings, making this investigation less reliable, especially in dilute urine samples (Tomson & Porter, 2002). The presence of hyaline red cell casts on microscopy is indicative of glomerulonephritis (Kumar & Clark, 2005) rather than the urinary tract as the site of bleeding. Further cytology, imaging and cystoscopy can aid determining other causes presenting as asymptomatic microscopic haematuria such as IgA nephropathy, thin glomerular basement membrane disease and Alportââ‚¬â„¢s syndrome (Kumar & Clark, 2005).
Cultures may help rule out UTIs as a cause of haematuria, normally indicated by the presence of white cells in urine and raised ESR, CRP or WCC. Further tests must be combined with other clinical findings to determine the cause of haematuria; e.g. biochemistry for raised serum creatinine alongside proteinuria and hypertension indicates renal disease. Cytology, voided markers and cystoscopy are alternative investigations used for diagnosis of cancers and for visualising the urinary tract for lesions causing haematuria (Rodgers, et al., 2006).
Imaging techniques may be performed in further investigation, each with its uses and limitations. Abdominal radiographs may detect radiopaque calculi, IV urography/pylography detect lesions though have a risk of allergy to dyes used. USS may detect lesions but is particularly user-dependent, CT is used to further investigate and localise lesions picked up on IVU and urinary stones. MRI is costly and less available than other modalities so is not used routinely (Rodgers, et al., 2006). Immunology and biopsies are indicated in particular circumstances, where symptoms and other test results indicate their use.
Figure 1 ââ‚¬" adapted from (Thomas, et al., 2007)
Figure 2 ââ‚¬" adapted from (Thomas, et al., 2007)
Microscopic asymptomatic haematuria found on routine new admission dipstick may be physiological (Rockall, et al., 1997) or unexplained -50% of people with flank pain without stones have microscopic haematuria (Malmstrom, 2003), while studies show that of those fully investigated for AMH, a cause was found in as few as 32% (Grossfeld, et al., 2001). Those with physiological haematuria with a negative dipstick 2 weeks later may be discharged with advice to return if symptoms develop if a nephrological opinion concurs (Rockall, et al., 1997).
Bladder cancers rarely present with AMH alone, and have been found to be no less advanced than malignancies presenting with macroscopic haematuria (Longmore, et al., 2008) (Mohr, et al., 1987), meaning treatment options are not altered. Recurrent UTIs causing macroscopic haematuria and heavy painless haematuria should both be urgently referred to a haematuria clinic within 2 weeks (Urology, 2013). The presence of significant pathology associated with haematuria increases with age (Ritchie, et al., 1986), so The Oxford Handbook recommends immediate referral to a Urologist and an USS, with a nephrology referral only indicated in cases suspicious of glomerulonephritis (Longmore, et al., 2008) (Rodgers, et al., 2006).
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Any episode of symptomatic or macroscopic haematuria needs further investigation, with pathology being more likely (Kelly, et al., 2009) (Rockall, et al., 1997). Result from other tests may influence a renal or urological referral depending on the proposed source of haematuria. Symptomatic patients <40y/o and all patients >40y/o with haematuria, symptomatic or otherwise, require referral to a urologist. Asymptomatic patients do not require referral (Anderson, et al., 2008) (Kelly, et al., 2009). A nephrological referral should be considered for those who have no urological pathology but with renal symptoms such as falling GFR, proteinuria, hypertension or with pre-existing kidney disease (Anderson, et al., 2008)(See appendix 2).
Underlying pathology cannot be excluded in those meeting neither urological or nephrological referral criteria, nor those with negative investigation findings. Longer term monitoring of LUTS, gross haematuria and changes in renal symptoms mentioned above is therefore appropriate in these cases (Anderson, et al., 2008). Within primary care, full investigations are repeated after 2 years for patients with macroscopic haematuria and after 1 year for those with microscopic haematuria, when no cause is found after initial investigation (Dentistry, 2006). Patients in higher risk groups such as smokers and those exposed to chemical exposures must receive follow-up appointments due to haematuria sometimes presenting years before bladder cancer diagnosis (Grossfeld, et al., 2001) (Hiatt & Ordonez, 1994). Repeated cytology may detect carcinoma-in-situ and high-grade tumours which could benefit from early intervention and treatment (Grossfeld, et al., 2001). For patients whom you have high suspicion of disease or persistent haematuria, repeat investigation may be warranted for 3 years, after which time the patient may be discharged if no cause is found through repeated investigation (Grossfeld, et al., 2001).
Alternatively urine cytology, blood pressure and urinalysis may be repeated at 6, 12, 24 and 36 months, during which time urological referral is advised if changes are found or symptoms arise (Grossfeld, et al., 2001) (Wollin, et al., 2009).
Haematuria can vary both in cause and severity. The presence of haematuria cannot be considered in isolation, and must be taken in context with a good history and examination in order to choose the most appropriate care pathway for the patient, avoiding unnecessary invasive investigation and treatment where possible. Reassuring the patient of the possible benign causes of haematuria can make the investigation process less stressful.
Microscopic haematuria is the presence of >5 RBCs seen on microscopy without transient cause or contamination. Macroscopic haematuria is the presence of visible blood in the urine. Both macroscopic and microscopic haematuria can be symptomatic or asymptomatic. Cytology should be performed on anyone with microhaematuria.
Nephrological referral is indicated in patients with signs of renal disease such as oedema and hypertension, and for those with red cell casts or elevated creatinine on further investigation (Wollin, et al., 2009). Urological referral is indicated in patients >40y/o or those with symptomatic haematuria (Kelly, et al., 2009) (Anderson, et al., 2008).
Patients with negative investigations should be followed up at 6, 12, 24 and 36 months with repeat urinalysis, cytology and BP checks. Should these findings deteriorate or symptoms appear, appropriate referral to a urologist or nephrologist is required to find and treat the cause of haematuria. If no positive findings occur after 3 years of investigation, the patient can be discharged (Wollin, et al., 2009) (Grossfeld, et al., 2001).
Anderson, J. et al., 2008. Joint Consensus Statement on the Initial Assessment of Haematuria, s.l.: BAUS/RA Guidelines.
Britton, J., Dowell, A. & Whelan, P., 1989. Dipstick hematuria and bladder-cancer in men over 60: results of a community study. BMJ, Volume 299, pp. 1010-1012.
Dentistry, B. a. t. L. Q. M. S. o. M. a., 2006. Haematuria. Management of Adults in Primary Care, s.l.: Clinical Effecticeness Group.
Fracchia, J. et al., 1995. Evaluation of asymptomatic microhematuria. Urology, Volume 46, pp. 484-489.
Grossfeld, G. D. et al., 2001. Asymptomatic Microscopic Hematuria in Adults: Summary of the AUA Best Practice Policy Rcommendations. American Family Physician, 63(6), pp. 1145-1154.
Grossfeld, G. et al., 2001. Evaluation of asymptomatic microscopic hematuria in adults: the American Urological Association best practice policy - part II: patient evaluation, cytology, voided markers, imaging, cystoscopy, nephrology evaluation, and follow-up. Urology, Volume 57, pp. 604-610.
Hiatt, R. & Ordonez, J., 1994. Dipstick urinalysis screening, asymptomatic microhaematuria, and subsequent urological concers in a population-based sample.. Cancer Epidemiology, Biomarkers & Prevention, 523(3), pp. 439-443.
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Decision algorithm for the investigation of non-visible haematuria and the referral criteria
adopted by the British Association of Urological Surgeons and the Renal Association. GFR,
glomerular filtration rate; PCR, protein:creatinine ratio; ACR, albumin:creatinine ratio. (Kelly, et al., 2009)