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Haematuria: History Taking and Differential Diagnoses

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Overview

Haematuria describes blood in the urine. Currently, haematuria should only be tested if clinically indicated. There is no evidence to support screening for haematuria in the general population. As little as 1 mL of blood can discolour 1 L of urine.

Definitions

Haematuria may be described as:

  • Visible (macroscopic or gross) haematuria: urine that is visibly discoloured by blood (may be brown to red)
  • Non-visible (microscopic) haematuria: urine that is not visibly discoloured, but testing identifies the presence of blood (e.g. urine dipstick or 3+ red blood cells per high-powered field in microscopy)

Causes

Common causes of haematuria include:

Infective causes include:

  • Cystitis
  • Tuberculosis
  • Prostatitis
  • Urethritis
  • Schistosomiasis

Malignant causes may include:

Inflammatory causes include:

Traumatic causes:

  • Accidental trauma
  • Catheter or foreign body insertion
  • Prolonged and severe exercise
  • Rapid emptying of the bladder (e.g. after catheterising for acute retention)

Structural causes:

Other causes:

  • Menstruation
  • Abuse
  • Some foods (e.g. beetroot)

History Taking

History of presenting complaint

With each presenting complaint, ask the following:

  • When did it start?
  • Did it come on suddenly or gradually?
  • Is it continuous or intermittent?
  • Has this ever happened before?

Ask questions about haematuria:

  • How much blood do they think they are passing?
  • What colour is their urine?
  • When does the blood come out?
    • Initial haematuria (blood at the start of the stream) and terminal haematuria – suggests urethral, prostate, or bladder neck pathology
    • Total haematuria (blood throughout the stream) – suggests bladder, ureter, or kidney pathology
  • Are there any clots?
  • Have they had any urinary retention?

Associated symptoms

  • Do they have any pain?
    • Use SOCRATES
    • Flank pain or loin-to-groin pain suggests renal stones
    • Vague abdominal pain can suggest polycystic kidney disease
  • Do they have any dysuria?

Do they have any lower urinary tract symptoms (LUTS)? These can suggest urinary outflow obstruction, such as BPH or prostate cancer:

  • Do they have increased urinary frequency?
  • Do they have urinary urgency?
  • Is there a poor urinary stream?
  • Do they need to strain to pass urine?
  • Do they have a feeling of incomplete bladder emptying?
  • Do they need to wake up at night to pass urine?

Features suggesting infection:

  • Are they passing any discharge?
  • Do they have any fever?

Other features to explore:

  • Has there been any recent vigorous physical activity? – even if exercise-induced haematuria may be possible, other causes must be ruled out
  • Are there any features of nephrotic syndrome?
    • Peripheral oedema?
  • Are there features of a systemic inflammatory disorder?
    • Joint pains?
    • Skin rashes?
  • Have they recently had a sore throat?
  • Are there any constitutional symptoms? – may suggest malignancy or systemic inflammation:

Past medical history

Questions include:

  • Do they have any other medical conditions?
  • Have they ever had any surgery?
  • Do they take any regular medications?
    • Do they take any anticoagulants?
    • Do they take NSAIDs such as ibuprofen?
  • Do they take any over-the-counter medications, herbal remedies, or supplements?

Family history

Is there any family history of:

  • Similar symptoms?
  • Kidney, bladder, or prostate cancer?
  • Kidney problems in general?

Allergy history

  • Are they allergic to anything?
    • What happens during the allergic reaction?

Social history

  • Do they smoke?
    • If so, how much and how long?
  • Do they drink alcohol?
    • If so, how much and how long?
  • Do they use any illicit drugs?
    • If so, how much and how long?
  • What is their occupation? Have they ever been exposed to chemicals?
    • Some chemicals such as benzene, dyes, and aromatic amines are linked to bladder cancers
  • Has there been any recent foreign travel?
    • May suggest an infective cause such as schistosomiasis

Physical Examination

Overview

Examinations to consider are:

  • Vital signs:
    • Fever may suggest an infection
    • Hypertension may suggest a cause of nephritic syndrome
    • Hypotension and tachycardia may suggest severe blood loss
  • Abdominal examination:
    • Cachexia may suggest malignancy
    • Flank or costovertebral tenderness may suggest pyelonephritis or malignancy
    • Flank masses may suggest malignancy
    • Suprapubic tenderness may suggest cystitis and urinary retention
  • Digital rectal examination – may be considered in men to assess for:
    • Prostatic enlargement, suggesting BPH or prostate cancer
    • Tenderness – suggesting prostatitis

Investigations

Initial tests

Initial tests include:

  • Urine dipstick – a useful initial bedside test:
    • Confirms haematuria and differentiates from non-haematuria-producing causes of discoloured urine (e.g. certain foods)
    • Proteinuria suggests glomerulonephritis
    • Leukocytes suggest inflammation
    • Nitrites suggest infection
  • Urine microscopy:
    • ≥3 red blood cells per high-power field suggests non-visible haematuria
    • Visible haematuria is usually obvious on microscopy
    • Red cell casts suggest a glomerular or tubular source of bleeding
    • White blood cells and white cell casts suggest inflammation
    • Crystals suggest renal stones
    • Bacteria suggest a UTI
  • Urine cultures:
    • Identifies the causative pathogen in infection
  • Urine cytology:
    • If malignancy is suspected, renal cell and prostate cancers are not detected by this test
  • Full blood count (FBC):
    • May show anaemia suggesting severe bleeding
    • May show leukocytosis suggesting infection or renal stones
  • Urea and electrolytes (U&Es) and estimated glomerular filtration rate (eGFR):
    • May show derangements suggesting renal dysfunction
  • C-reactive protein:
    • May be elevated in inflammation
  • Coagulation testing:
    • May be considered in patients who take anticoagulants or where coagulopathy is suspected
  • Imaging (see below).

Imaging

Patients with haematuria should have imaging of the:

  • Upper urinary tract (kidneys and ureters) – done via CT urogram or ultrasound:
    • An ultrasound scan is commonly used but is less accurate
    • A CT urogram is preferred in those at high risk of malignancy
  • Lower urinary tract (bladder, urethra, and prostate) – done via flexible cystoscopy

Referral

NICE guidelines

Refer patients via a suspected cancer pathway (2-week-wait) if they are:

  • Aged ≥45 and have:
    • Unexplained visible haematuria without a UTI
    • Visible haematuria that persists or recurs after successfully treating a UTI or
  • ≥60 and have unexplained non-visible haematuria and either:
    • Dysuria or
    • A raised white cell count on a blood test

Consider a non-urgent referral for bladder cancer in those ≥60 with recurrent or persistent UTIs.

Differential Diagnoses

Urinary tract infection (UTI)

  • There may be features of infection such as dysuria, and polyuria
  • Fever and suprapubic tenderness may be seen
  • Urinalysis is positive for nitrites and may also be positive for leukocytes

Acute pyelonephritis

  • Patients generally have a fever, loin pain, nausea, and vomiting
  • Costovertebral (renal angle) tenderness
  • Urinalysis is positive for nitrites and may be positive for leukocytes

Benign prostatic hyperplasia

  • Lower urinary tract symptoms (LUTS) may be present, such as hesitancy, polyuria, incomplete emptying, and weak stream
  • A digital rectal exam may reveal a smoothly enlarged prostate

Prostate cancer

  • LUTS may be present
  • Unexplained weight loss may be present
  • A digital rectal exam may reveal a nodular, irregular, and/or diffusely enlarged and hard prostate
  • There may be a family history of similar features

Bladder cancer

  • Most patients present with painless visible haematuria
  • There may be a history of smoking, exposure to chemicals (such as aromatic amines), or a history of schistosomiasis
  • There may be a pelvic mass, however, there are often no abnormal findings on a physical examination

Trauma-induced haematuria

  • Flank trauma or fractured lower ribs suggest renal trauma
  • Pelvic trauma and/or an inability to pass urine suggests bladder trauma
  • Genital trauma may suggest urethral trauma

Coagulopathy or anticoagulant use

  • Patients may have a history of anticoagulant use (e.g. atrial fibrillation or mechanical valves)
  • There may be a history of easy bruising and prolonged bleeding
  • Coagulation studies may be deranged
  • Other causes need to be ruled out

Autosomal dominant polycystic kidney disease (ADPKD)

  • Most commonly presents between 30-60 years with haematuria and chronic loin pain
  • Patients may be hypertensive and have recurrent UTIs
  • Enlarged kidneys may be felt on abdominal palpation
  • Renal ultrasound shows cystic lesions
  • There may be a family history of similar features

Acute nephritic syndrome

  • Causes include anti-glomerular basement membrane disease (Goodpasture’s syndrome), IgA nephropathy, post-streptococcal glomerulonephritis, lupus nephritis, and vasculitis
  • See nephritic syndrome for more information
  • Haematuria, proteinuria, hypertension, and oliguria may be present
  • IgA nephropathy presents 1-2 days following an upper respiratory tract infection. There may also be episodes of recurrent visible haematuria
  • Post-streptococcal glomerulonephritis presents 1-2 weeks after an infection with Streptococcus species

Clot retention

  • Clots may be present in the urine
  • Urinary obstruction may be present
  • Catheterisation using a 3-way catheter and a bladder washout until the urine runs clear should be performed

Alport syndrome

  • Usually seen in childhood with non-visible haematuria, progressive renal failure, sensorineural deafness, and ocular complications such as lenticonus or retinitis pigmentosa
  • There may be a family history of similar features

Extrapulmonary tuberculosis

  • Features similar to a UTI are seen (e.g. dysuria and polyuria)
  • Urinalysis shows pyuria but no bacteria (sterile pyuria) is seen
  • Acid-fast staining is positive

Renal stones

  • Patients may have sudden-onset severe loin-to-groin pain and nausea
  • Costovertebral (renal) angle tenderness may be seen
  • There may be a family history
  • Urinalysis shows haematuria, and pyuria, and may show the presence of crystals
  • A non-contrast CT of the kidneys, ultrasound, and bladder (CT KUB) may show stones

Menstruation

  • No urinary symptoms are present
  • An examination is normal
  • There may be a history of cyclic haematuria
  • Diagnosis is often clinical

Exercise-induced haematuria

  • There is a recent history of vigorous exercise
  • Physical examination is normal and urinalysis should show red blood cells only
  • Haematuria resolves in around 3 days

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