Haematuria (Painless Microscopic)

• Defined as 3 or more RBC per High-Power Field
• The use of dipstick readings alone to prompt further imaging or endoscopic evaluation for haematuria is not recommended due to reliability of the test with significant confounding factors1-3. A positive dipstick result should prompt workup with 3 samples for urine microscopy which has the added benefit of examining red cell morphology and increased accuracy1-5.

• It should be noted that in Sweden a national policy was adopted in 1999 of abandoning investigation of individuals with asymptomatic microscopic haematuria. A report in 2023 33 concluded that this policy did not adversely affect that survival of patients with bladder cancer in Sweden. While this approach may be regarded as extreme, the risk stratification of patients (low, intermediate and high) and the subsequent different management of each classification -see here RISK STRATIFICATION for URINARY MALIGNANCY – would appear to be a satisfactory compromise
• Malmström, P.U. and G. Truls, Abandoning testing for asymptomatic microscopic haematuria in Sweden - a long-term follow-up. Scand J Urol, 2023. 58: p. 109–114. RISK STRATIFICATION for URINARY MALIGNANCY

• Transient microscopic haematuria may be induced by a variety of activities, such as vigorous exercise, menstruation, mild trauma, sexual intercourse. These causes should be excluded prior to diagnostic work up of microscopic haematuria.
• Following exclusion of transient causes, it is recommended to repeat microscopy x 3 and advise to avoid the above confounders 1-3, 5.

• It is important to distinguish glomerular from non-glomerular microscopic haematuria Glomerular vs non-glomerular haematuria
• Tests for renal disease include measurement of blood pressure, detection of proteinuria and urinary red cell casts and blood urea and electrolyte levels.
• However, patients should still proceed to risk stratification for malignancy and urologic workup as indicated concurrent to renal workup 1

• It is important to risk stratify patients prior to the selection of appropriate diagnostic investigations to balance advantages with potential harms and overevaluation 1, 3, 6-12.
• Microscopic haematuria is common while underlying urinary malignancy is infrequent. Risk stratification is required to avoid risks of evaluation (procedural, radiation etc) and correctly identify patients who may benefit from earlier, more extensive evaluation 3
• There is insufficient evidence to support the use of urinary bio-markers to detect transitional cell carcinomas 1, 4, 13, 14.
• Urine cytology is not recommended in the workup of patients with microscopic haematuria 1, 4. Urologists may decide to request cytology on a high suspicion of carcinoma in situ (symptomatic microscopic haematuria)1.
• Risk stratification and suggested management here is as per the 2025 AUA/SUFU guideline update 3.

Patients at negligible/low-risk of urinary malignancy 0%-0.4% 3:

• Men <40 year of age
• Women <60
• Patients who have never smoked or smoked <10 pk yr
• 3-10 RBC/HPF
• No previous macroscopic haematuria 
• No other risk factors for urothelial cancer  

Patients at intermediate risk of urinary malignancy 0.2-3.1%3:

• Men 40-59
•  Women >/= 60 
• 10-30 pk yr smokers
• 11-25 RBC/HPF
• One or more other risk factors for urothelial cancer
• Previously low risk and persistent Painless Microscopic Haematuria with 3-25 RBC/HPF.

Patients at high risk of urinary malignancy 1.3%-6.3% 3:

• Men >60
• Women should not be considered high risk on age criteria alone
• >30 pk yr smokers
• >25 RBC/HPF
• History of macroscopic haematuria
• Previously low risk but >25 RBC/HPF on re-evaluation.

• Ultrasound is accurate for evaluation of upper tract disease 15, 16, especially for renal cell carcinomas >1cm 13, 17, 18 but may miss some upper tract transitional cell carcinomas, particularly those too small to cause obstruction 18.
• The incidence of upper tract disease in asymptomatic microscopic haematuria is very low 1, 3, 16-19.
• Ultrasound has the benefit of no ionising radiation exposure to the patient, no risk of contrast allergy and wide availability 3, 13.
• Rare missed or subsequent cancers following evaluation with ultrasound in a large microscopic haematuria cohort were shown at follow up to be early-stage disease suggesting timely diagnosis 16.
• Abnormal US findings may prompt further workup with CT 15, 16
• Cystoscopy remains the diagnostic gold standard for evaluation of the lower urinary tract in patients with intermediate or high risk asymptomatic microscopic haematuria 3, 16. Across prospective studies and systematic review data, cystoscopy demonstrates consistently high sensitivity (approximately 87–100%) and very high negative predictive value (approximately 98–100%) for bladder cancer detection, outperforming any imaging modality for intravesical disease 20. Its key strength lies in direct visualisation of the bladder mucosa, enabling detection of small papillary tumours and flat lesions such as carcinoma in situ, which are frequently occult on ultrasound (US) and CT urography (CTU) 20, 21.
• Cystoscopy is invasive and associated with patient discomfort, risk of urinary tract infection, haematuria and dysuria[20]. False-positive findings may lead to unnecessary downstream interventions such as transurethral resection with benign histology, particularly in patients with low pre-test probability of malignancy 21.
• Cystoscopy does not assess the upper urinary tract and therefore cannot replace imaging when renal or ureteric pathology must be excluded 21.

• Radiographic (conventional) Intravenous Urography (IVU) is  no longer recommended for workup of painless microscopic haematuria 6, 13, 22, 23, unless CT is unavailable.

• CT Urography is accurate for assessment of upper tract transitional cell carcinoma 11, 13, 24, 25.
• Some guidelines do not recommend routine use of CT urography in microscopic haematuria 6, 21, 26, 27.
• Diagnostic yield of CT urography in the workup of Painless Microscopic Haematuria in patients with negative cystoscopy is low 0.6% 28, suggesting a stepwise diagnostic approach may be preferred, following counselling in patients who prefer to avoid CT urography, acknowledging the risks of radiation and contrast reactions.
• Cystoscopy remains the diagnostic gold standard for evaluation of the lower urinary tract in patients with haematuria. Across prospective studies and systematic review data, cystoscopy demonstrates consistently high sensitivity (approximately 87–100%) and very high negative predictive value (approximately 98–100%) for bladder cancer detection, outperforming any imaging modality for intravesical disease 20. Its key strength lies in direct visualisation of the bladder mucosa, enabling detection of small papillary tumours and flat lesions such as carcinoma in situ, which are frequently occult on ultrasound (US) and CT urography (CTU) 20, 21.
• Cystoscopy is invasive and associated with patient discomfort, risk of urinary tract infection, haematuria and dysuria 20. False-positive findings may lead to unnecessary downstream interventions such as transurethral resection with benign histology, particularly in patients with low pre-test probability of malignancy 21.
• Cystoscopy does not assess the upper urinary tract and therefore cannot replace imaging when renal or ureteric pathology must be excluded 21.

• Repeat urine microscopy is recommended in 6 or 12 months following negative investigation and discussion with the patient 3.
• If the patient develops visible haematuria in the meantime, then suggest further urology workup1, 27, 29.
• Some guidelines do not recommend routine follow up of lower risk patients following negative assessment 13.
• Low numbers of newly diagnosed malignancies have been observed in patients with persistent microscopic haematuria and prior negative evaluation, particularly in low risk categories 30-32.

• Microscopic examination of urinary sediment must always follow dipstick-positive findings to verify microhematuria
• The absence of microscopic RBCs in strongly dipstick-positive samples suggests alternative causes, eg, myoglobinuria, hemoglobinuria from lysed erythrocytes, or other causes of pseudohematuria

• Glomerular causes of microscopic haematuria is usually associated with by proteinuria, casts, or dysmorphic RBCs, and indicates at least moderate kidney disease

• Nonglomerular causes typically demonstrate normal RBCs on microscopic urinalysis without proteinuria or casts.