What are the next steps for a patient with hematuria and anemia despite a negative urinalysis (UA)?

Management of Hematuria with Anemia Despite Negative Urinalysis

For patients with hematuria and anemia despite a negative urinalysis, a comprehensive urologic and nephrologic evaluation is necessary, including imaging studies, cystoscopy, and specialist referral to identify the underlying cause.

Diagnostic Approach

Initial Assessment

• A negative urinalysis does not rule out significant urologic or nephrologic disease, as some conditions causing hematuria may present intermittently 1
• The combination of hematuria and anemia indicates ongoing blood loss that requires thorough investigation, even with a negative UA 1, 2
• Determine if there was previous documentation of hematuria (gross or microscopic) as this affects the diagnostic approach 1

Laboratory Evaluation

• Complete blood count to assess the severity of anemia 1
• Serum creatinine to evaluate renal function 1
• Urine culture to exclude infection that might not be evident on initial urinalysis 1
• Urine cytology to evaluate for malignancy, especially in older patients 1
• Consider testing for proteinuria to assess for glomerular disease 3

Imaging Studies

• CT urography is the preferred initial imaging modality for comprehensive evaluation of the upper urinary tract in patients with hematuria and anemia 1, 3
• MR urography is an alternative if CT is contraindicated 1
• Renal ultrasound with retrograde pyelography can be considered if CT and MR are not feasible 1

Specialist Referral

• Urgent urologic referral is mandatory for patients with hematuria and anemia, even if urinalysis is negative 1, 4
• Nephrology referral should be considered if there is evidence suggesting glomerular disease (proteinuria, hypertension) 1, 3

Specific Diagnostic Considerations

Urologic Causes to Consider

• Urinary tract malignancy (bladder, kidney, ureter) may cause intermittent bleeding 1, 4
• Urolithiasis may cause intermittent hematuria with negative UA between episodes 5
• Ureteric strictures can cause chronic hematuria and anemia 6
• Benign prostatic hyperplasia can cause hematuria but should not be assumed to be the sole cause without proper evaluation 3

Nephrologic Causes to Consider

• Glomerular diseases may present with intermittent hematuria 3
• IgA nephropathy and thin basement membrane disease can cause episodic hematuria 2

Follow-up Recommendations

• If initial evaluation is negative, repeat urinalysis at 6,12,24, and 36 months 1, 7
• Monitor blood pressure at each follow-up visit 7
• Immediate re-evaluation is warranted if any of the following occur:
  • Recurrent gross hematuria
  • Abnormal urinary cytology
  • Worsening anemia
  • Development of new symptoms 7

Important Considerations

• Do not attribute hematuria solely to anticoagulant or antiplatelet medications without thorough investigation 1
• Persistent or recurrent hematuria after initial negative evaluation warrants repeat evaluation within three to five years 8
• Changes in clinical scenario (increase in degree of hematuria, development of gross hematuria, pain) warrant earlier re-evaluation 8
• The presence of anemia suggests significant blood loss that requires more urgent and thorough evaluation 4

Pitfalls to Avoid

• Do not assume a negative urinalysis rules out significant urologic disease 1, 2
• Do not delay urologic referral while waiting for other test results 1
• Do not attribute hematuria solely to benign conditions (like BPH) without proper evaluation 3
• Do not neglect follow-up even if symptoms temporarily resolve 7