Haematuria

Definition of Haematuria: the presence of blood in the urine.

Macroscopic (gross) haematuria: the patient has seen blood.

Microscopic or dipstick haematuria: blood identified by urine microscopy or by dipstick testing, either in association with other urological symptoms - symptomatic microscopic haematuria - or during a routine medical examination (e.g. for insurance purposes) - asymptomatic microscopic haematuria.

Microscopic haematuria has been variably defined as 3 or more, 5 or more, or 10 or more red blood cells (RBCs) per high-power field.

Urine dipsticks test for heme (i.e. they test for the presence of haemoglobin and myoglobin in urine). Heme catalyses the oxidation of orthotolidine by an organic peroxidase, producing a blue coloured compound. Dipsticks are capable of detecting the presence of haemoglobin from 1 or 2 RBCs.

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  False +ve urine dipstick: occurs in the presence of myoglobinuria, bacterial peroxidases, povidone, hypochlorite.
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  False -ve urine dipstick (rare): occurs in the presence of reducing agents (e.g. ascorbic acid prevents the oxidation of orthotolidine).

Is microscopic or dipstick haematuria abnormal?

A few RBCs can be found in the urine of normal people. The upper limit of normal for RBC excretion is 1 million per 24h (as seen in healthy medical students). In healthy male soldiers undergoing yearly urine examination over a 12-yr period, 40% had microscopic haematuria on at least 1 occasion and 15% on 2 or more occasions. Transient microscopic haematuria may occur following rigorous exercise, sexual intercourse, or from menstrual contamination.

The fact that the presence of RBCs in the urine is normal explains why a substantial proportion of patients with microscopic and dipstick haematuria, and even macroscopic haematuria will have normal haematuria investigations (i.e. no abnormality is found). No abnormality is found in approximately 50% of subjects with macroscopic haematuria and 70% with microscopic haematuria, despite full conventional urological investigation (urine cytology, cystoscopy, renal ultrasonography, and IVU).¹

Haematuria causes and investigation

Urological causes of haematuria

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  Cancer: bladder (TCC, SCC), kidney (adenocarcinoma), renal pelvis and ureter (TCC), prostate
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  Stones: kidney, ureteric, bladder
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  Infection: bacterial, mycobacterial (TB), parasitic (schistosomiasis), infective urethritis
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  Inflammation: cyclophosphamide cystitis, interstitial cystitis
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  Trauma: kidney, bladder, urethra (e.g. traumatic catheterization), pelvic fracture causing urethral rupture
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  Renal cystic disease (e.g. medullary sponge kidney)
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  Other urological causes: BPH (the large, vascular prostate), loin pain haematuria syndrome, vascular malformations
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  Nephrological causes of haematuria tend to occur in children or young adults and include, commonly, IgA nephropathy, postinfectious glomerulonephritis; less commonly, membranoproliferative glomerulonephritis, Henoch Schanlein purpura, vasculitis, Alport's syndrome, thin basement membrane disease, Fabry's disease, etc.
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  Other medical causes of haematuria: include coagulation disorders congenital (e.g. haemophilia), anticoagulation therapy (e.g. warfarin); sickle cell trait or disease; renal papillary necrosis; vascular disease (e.g. emboli to the kidney cause infarction and haematuria).
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  Nephrological causes are more likely in the following situations: children and young adults; proteinuria; red blood cell casts.

Urological investigation of haematuria

Conventional urological investigation involves urine culture (where, on the basis of associated cystitis symptoms urinary infection is suspected), urine cytology, cystoscopy, renal ultrasonography, and IVU.

Diagnostic cystoscopy:  Nowadays this is carried out using a flexible, fibreoptic cystoscope, unless radiological investigation demonstrates a bladder cancer, in which case one may forego the flexible cystoscopy and proceed immediately to rigid cystoscopy and biopsy under anaesthetic (transurethral resection of bladder tumour (TURBT).

Should cystoscopy be performed in patients with asymptomatic microscopic haematuria?

The AUA's Best Practice Policy on Asymptomatic Microscopic Hematuria recommends cystoscopy in all high-risk patients (high risk for development of TCC) with microscopic haematuria (see risk factors below). In asymptomatic, low-risk patients it states that it may be appropriate to defer cystoscopy but if this is done, urine should be sent for cytology. However, the AUA also states that the decision as to when to proceed with cystoscopy in low-risk patients with persistent microscopic hematuria must be made on an individual basis after a careful discussion between the patient and physician.

It is our policy to inform such patients that the likelihood of finding a bladder cancer is low, but nevertheless we recommend flexible cystoscopy. The patient then makes a decision as to whether or not to proceed with cystocopy based on their interpretation of low risk.

If no cause for haematuria is found (microscopic or macroscopic) is further investigation necessary?

Some say yes, quoting studies that show serious disease can be identified in a small number of patients where, in addition, retrograde ureterography, endoscopic examination of the ureters and renal pelvis (ureteroscopy), contrast CT, and renal angiography were done.
Others say no, citing the absence of development of overt urological cancer during 2 -4 year follow-up in patients originally presenting with microscopic or macroscopic haematuria (though without further investigations).

When urine cytology, cystoscopy, renal US, and IVU are all normal, we perform CT scanning of the kidneys and ureters and retrograde ureterography in: 

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  patients at high risk for TCC^*
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  where microscopic or dipstick haematuria persists at 3 months
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  where macroscopic haematuria persists