Haematuria

You will regularly see patients with blood in their urine, most often picked up incidentally on a urine drip. Your initial assessment should aim to identify whether this is due to a UTI (or other transient cause) and whether it is urological or nephrological with the help of measuring the patient’s blood pressure, bloods (FBC, U&Es, CRP) and a urine PCR. Occasionally, patients may complain of significant haematuria and an ABCDE assessment is required to assess and manage this. Here we’ve focussed on immediate investigations, management and the pathways these patients should follow.

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Definition of haematuria

  • Visible haematuria (VH) is known as macroscopic or gross haematuria
  • Non-visible haematuria is known as microscopic or urine dipstick positive haematuria. It may be symptomatic (sNVH) or asymptomatic (aNVH). Up to 5% of patients with aNVH are found to have a urinary malignancy.
  • Significant haematuria is any episode of VH, sNVH (in the absence of a UTI or transient cause) or persistence in aNVH (across 2 of 3 urine dipstick).
  • All patients with significant haematuria (with aNVH in ≥40 years) should be considered for urology referral

Common causes of haematuria

As you can imagine, blood may originate from anywhere in the urinary tract from the kidneys to the urinary meatus. The most common are:

  • UTIs (by far)
  • Benign prostate hypertrophy
  • Renal stones
  • Urethritis
  • Bladder tumours
  • Prostate cancer

Haematuria is a very broad topic that encompasses a wide differential diagnosis, from Urinary Tract Infection (UTI) to cancer (figure 1). Therefore, it is best to separate it into microscopic or macroscopic haematuria.

haematuria causes
Figure 1: Causes of haematuria other than UTIs (source)

Immediate management

Visible haematuria can sometimes be a medical emergency. If there is evidence of cardiovascular collapse or acute urinary retention, the patient requires immediate management.

In patients with cardiovascular compromise:

• Resuscitate the patient with the aim of volume replacement, treatment of coagulopathy and achieving haemostasis.
• Emergency surgical intervention may be needed if there is significant bleeding of the bladder
• Blood transfusion may also be required.

In patients with acute urinary retention (usually secondary to a blood clot):

• Insert a 3-way urinary catheter (consult a senior if you have any problems catheterising)
• If a urethral injury, bladder injury or a fractured penis is suspected, obtain a urethrogram before attempting catheterisation a
• Avoid suprapubic catheterisation or bladder aspiration to prevent seeding of a potential bladder tumour

If there are no indications for admission ensure that the patient is discharged safely and that they are advised on the management of haematuria as well as when to seek medical help.

Visible haematuria

Visible haematuria, as the name suggests, is visible blood in the urine (usually pink or red)

Causes
1. Urologic malignancy
• Bladder cancer
• Prostate cancer
• Renal cell carcinoma

2. Renal disease (Non-malignant)
Glomerular disease
• Ig A nephropathy
• Alport syndrome
• Lupus nephritis
• Haemolytic uraemic syndrome

Non-glomerular renal disease
• Hydronephrosis
• Acute tubular necrosis
• Renal cyst
• Nephrolithiasis
• Hypercalciuria
• Polycystic kidney disease
• Renal artery stenosis
• Malignant hypertension

3. Non-renal causes (non-malignant)
• Sexual intercourse
• Trauma (blunt trauma or catheterisation)
• Menstrual contamination
• Vigorous exercise
• Urinary tract infection
• Prostatitis
• Endometriosis
• Menstruation
• Benign prostatic hyperplasia

4. Medications
• Cyclophosphamide
• Propafenone hydrochloride
• Aminoglycosides
• Amitriptyline
• Analgesics
• Aspirin
• Anti-epileptic drugs
• Oral contraceptives
• Warfarin
• Diuretics

5. Mimics (substances other than blood that cause urine discolouration)
Intrinsic
• Bilirubin
• Haemoglobin
• Myoglobin

Extrinsic
• Artificial food colouring
• Beetroot
• Rhubarb

Drugs
• Chloroquine
• Levodopa
• Phenytoin
• Quinine
• Sulfonoamides

History and examination
• Patients will typically complain of blood in their urine when they first present.

Important: Ensure that the patient is not in cardiovascular distress or experiencing acute urinary retention. These are medical emergencies and require urgent treatment.]

• Take a full urological history including symptoms of a UTI (frequency, urgency, dysuria), prostatic symptoms (hesitancy, dribbling and poor stream), nocturia, incontinence

• Obtain a full gynaecological and sexual history

• Enquire about red flags and systemic symptoms such as: nausea, vomiting, anorexia, fevers, night sweats, weight loss (Note: painless haematuria hints towards urological malignancy more so than painful haematuria)

• Ask about past medical history of urological issues including UTIs, family history, social history including smoking

• A general question of ‘have you had a water infection before?’ ‘Do you think it could be it again?’ Would usually open your door to more information.

Assess
• Blood pressure
• Abdomen for any tenderness

Perform
• DRE (to exclude tumours)

Investigations
1. Bloods
• FBC
• U&Es
• CRP
• Urine protein-creatinine ratio
• eGFR
• Coagulation
PSA (for male)
• Glucose
• HbA1c

2. Urinalysis
• Assess urine sample for visible haematuria
• Perform a urine dipstick to assess for haematuria
• Send a urine MC&S

Note since 2018, Public Health England had issued guidelines advising not to urine dip people over the age of 65, as a positive finding with nitrate, leukocytes, and blood, on an asymptomatic patient does not represent UTI, and does not require antibiotics treatment. This was a push to curb the overprescribing of antibiotics in the community and hospital settings.

3. Imaging
• CT KUB or US KUB
• Cystoscopy (to rule of malignancy)

Management
• The emergency management of gross haematuria is stated above and is aimed at achieving cardiovascular stability and free drainage of urine with or without a catheter.

Visible haematuria would always prompt a nurse give you a bleep and when that happens, follow the steps below:

Carry out an ABCDE assessment & stop the bleeding

Consider causes such as trauma and any use of anticoagulation or antiplatelets, which may be required to be withheld depending on the severity of bleeding. Do not stop a patient’s anticoagulation without discussion with your seniors (and haematology).

Generally speaking, if the urine is rosé in colour, then we can just increase the fluid intake and manage conservatively. A merlot colour means it is old blood, and therefore they may be blood clots in the bladder, and fresh red blood means fresh active bleeding.

The management for the latter two would be to insert a 3-way urinary catheter, by inserting a bigger catheter, you have a bigger balloon (20ml), this will act as a pressure point on the bleeding site. This is because most bleeding occurs from the neck of the bladder. Secondly, a 3-way catheter would also allow you to do bladder washout and irrigation, which is very useful in clearing blood clots inside the bladder.

Then you would do the investigations mentioned before including FBC, U&Es, Creatinine, eGFR, Coagulation, PSA (for male), Glucose, HbA1c, Blood pressure reading, and consider the use of CT KUB or Ultrasound KUB. Please also check for risk factors with urothelial cancers, especially smoking history.

Lastly, please contact Urology for them to consider any other management plan or doing cystoscopy to investigate the cause of the bleeding.

If strong suspicion of malignancy, ensure patient is referred via the 2 week wait cancer pathway.

Risk factors for urothelial cancer:
• Smoking
• Family history of bladder cancer
• Occupational exposure to carcinogens
• Pelvic irradiation
• Cyclophosphamide treatment
• Previous schistosomiasis infection

Potential signs of malignancy may include:
• In the absence of a urinary infection- urgency, frequency, dysuria, haematuria
• Unexplained weight lost
• Night sweats
• Loss of appetite
• Mass effect symptoms to abdomen (heaviness, pain, mass) or bladder (urge, urinary frequency)

Outisde the emergency setting

Treatment is based on the underlying cause
• Treat any UTIs
• Conservative management of stones or urological referral if they are unlikely to pass spontaneously
• Treat benign prostatic hyperplasia
• Remove any tumours
• Treat any glomerular diseases

Non-visible haematuria

According to the American Urological Association Guidelines Committee:

“The recommended definition of microscopic haematuria is 3 or more red blood cells per high-power microscopic field in urinary sediment from two of three properly collected urinalysis specimens. This definition accounts for some degree of haematuria in normal patients, as well as the intermittent nature of haematuria in patients with urologic malignancies.”

(Murphy, Crabtree, Jukkola and Soloway, 1981)” Quoted on Medscape (“What is the AUA recommended definition of microscopic haematuria?”, 2020).

Causes
1. Urologic malignancy
• Renal cell carcinoma
• Bladder cancer
• Prostate cancer

2. Renal disease (Non-malignant)
Glomerular disease
• Alport syndrome
• Lupus nephritis
• Haemolytic uraemic syndrome

Non-glomerular renal disease
• Hydronephrosis
• Acute tubular necrosis
• Renal cyst
• Nephrolithiasis
• Hypercalciuria
• Sickle cell disease
• Renal artery stenosis
• Malignant hypertension

3. Non-renal causes (non-malignant)
• Sexual intercourse
• Trauma (urethral injury or catheterisation)
• Menstrual contamination
• Vigorous exercise
• Urinary tract infection
• Prostatitis
• Digital Rectal Exam (DRE)

4. Medications
• Cyclophosphamide
• Aminoglycosides
• Amitriptyline
• Analgesics
• Aspirin
• Anti-epileptic drugs
• Oral contraceptives
• Warfarin
• Diuretics

5. Mimics (substances other than blood that cause urine discolouration)
• Presence of haemoglobin or myoglobin giving a false positive result. This is why microscopic confirmation of intact red blood cells is needed for a definitive diagnosis

History and examination
• The history and examination should focus on finding information that could help hint towards a cause such as urological malignancy, renal disease and non-malignant causes of microhaematuria.

Be aware of loin pain in the elderly. Microhaematuria and loin pain may prompt you to look for a renal stone but ensure you rule out a leaking abdominal aortic aneurysm.

• Take a full urological history including symptoms of a UTI (frequency, urgency, dysuria), prostatic symptoms (hesitancy, dribbling and poor stream), nocturia, incontinence

• Obtain a full gynaecological and sexual history

• Ask about a past medical history of urological issues including UTIs, family history, social history including smoking

• A general question of ‘have you had a water infection before?’ ‘Do you think it could be it again?’ Would usually open your door to more information.

Assess
• Blood pressure
• Abdomen for any tenderness, masses or renal pain

Perform
• A urethral and rectal examination for men
• A pelvic exam for women

Investigations
1. Bloods
• FBC
• U&Es
• CRP
• Urine protein-creatinine ratio
• eGFR
• Coagulation
• PSA (for male)
• Glucose
• HbA1c

2. Urinalysis
• Perform a urine dipstick to assess for haematuria. However, this should not be used as a diagnostic tool as microscopic assessment of urinary sediment is required for a diagnosis.

• A positive urine dipstick may be an incidental finding and so you must investigate if it is part of a normal variant or urinary tract infection (UTI) or part of something serious.

• Send a urine MC&S

Note since 2018, Public Health England had issued guidelines advising not to urine dip people over the age of 65, as a positive finding with nitrate, leukocytes, and blood, on an asymptomatic patient does not represent UTI, and does not require antibiotics treatment. This was a push to curb the overprescribing of antibiotics in the community and hospital settings.

3. Imaging
• The choice of imaging varies and there is no gold-standard imaging technique that has been agreed upon.

Choices include:
• Renal ultrasound
• Computed Tomography Urography
• Magnetic resonance urography
• Cystoscopy

A prompt referral to the Renal or Urology services in your hospital should be made once you have gathered all the information.

Summary of the common causes of haematuria

Common causesFeatures
UTILUTS +/- leucocytosis / nitrates on urine dip
Nephrolithiasis (Renal stones)Flank / loin pain or sudden acute onset
MalignancyPainless haematuria, check risk factors
Post interventionalRecent catheterisation or other procedures
Glomerulonephritis (or CKD)Look for nephritic syndrome, check BP, urine PCR & discuss with renal
VasculitisCheck ESR, CRP, ANA etc, look for family history and other risk factors.
Transient haematuriaUsually in young fit athletes
MensurationCheck LMP date, or ask the patient.
Sexual activity / TraumaClinical history
Common causes of haematuria and their features

References

  • Medscape.com. 2020. What Is The AUA Recommended Definition Of Microscopic Hematuria?. [online] Available here. [Accessed 10 June 2020].
  • Murphy, W., Crabtree, W., Jukkola, A. and Soloway, M., 1981. The Diagnostic Value of Urine Versus Bladder Washing in Patients with Bladder Cancer. Journal of Urology, 126(3), pp.320-322.
  • Saikat, R., 2020. What Are Causes For Blood In The Urine, Other Than Infection?. [image] Available here. [Accessed 10 June 2020].
  • Trust, C., 2020. Urology Referrals – Oxford University Hospitals. [online] Available here. [Accessed 11 June 2020].
  • Dynamed – Gross Hematuria – Approach to the Adult
  • Dynamed – Microhematuria – Approach to the Adult

Written by: Dr Alexander Tam (FY1)
Reviewed by Dr Sevgi Kozakli (FY4)
Edited by: Mudassar Khan (Y3 Medical Student)

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