What is the appropriate management for a patient presenting with hematuria and bilirubin in their urine?

Management of Hematuria with Bilirubinuria

The presence of both hematuria and bilirubin in the urine suggests hemolysis with hemoglobinuria rather than true hematuria, requiring immediate evaluation for hemolytic anemia with measurement of hemoglobin, haptoglobin, LDH, indirect bilirubin, and peripheral blood smear to assess for schistocytes and anemia. 1

Critical Initial Distinction

The combination of "hematuria" with bilirubinuria is highly unusual and demands careful interpretation:

• True hematuria (red blood cells in urine) does not cause bilirubinuria - bilirubin elevation occurs with hemolysis, not bleeding 1
• Hemoglobinuria from intravascular hemolysis can cause urine dipstick to be positive for "blood" without actual RBCs present, and this occurs alongside bilirubinuria from hemolysis 2
• Confirm whether urine microscopy shows actual RBCs versus hemoglobin pigment alone - this distinction is essential 1, 3

Immediate Laboratory Evaluation Required

When urine shows both blood and bilirubin, obtain urgently:

• Complete blood count to assess for anemia and thrombocytopenia (platelet count <150,000/mm³ or 25% reduction) 1
• Peripheral blood smear to look for schistocytes indicating microangiopathic hemolysis 1
• Haptoglobin level (will be reduced in hemolysis), LDH (elevated), and indirect bilirubin (elevated) 1, 2
• Direct Coombs test to confirm non-immune hemolytic anemia 1
• Urine microscopy to differentiate true hematuria (RBCs present) from hemoglobinuria (no RBCs, only hemoglobin pigment) 3, 2
• Serum creatinine to assess for acute kidney injury, which can occur with severe hemolysis 1, 2

If Hemolytic Anemia is Confirmed (Thrombotic Microangiopathy)

The triad of non-immune hemolytic anemia, thrombocytopenia, and renal involvement (hematuria/hemoglobinuria and/or proteinuria and/or elevated creatinine) indicates thrombotic microangiopathy requiring urgent differentiation between atypical HUS, TTP, and secondary causes. 1

• Immediately measure ADAMTS13 activity (severely deficient <10 IU/dL in TTP) - this test must be sent urgently before any plasma-based therapy 1
• Check stool for verocytotoxin-producing E. coli (VTEC) to exclude STEC-HUS 1
• Assess for complement-mediated aHUS if ADAMTS13 is normal and STEC is negative 1

Specific Considerations in Children

• In neonates with hemolysis and bilirubinuria, consider α-hemolytic bacteria (particularly Enterococcus) causing hemolysis through hemolysin secretion - obtain urine culture 4
• In children <1 year old with hemolysis, consider mutations in complement-unrelated genes (DGKE, WT1) and inborn errors of cobalamin metabolism (MMACHC) 1
• After strenuous exercise (especially kendo or running), consider march hemoglobinuria - urine will be occult blood positive without RBCs on microscopy, with hemosiderin in proximal tubules 2

If True Hematuria is Present (RBCs on Microscopy)

When microscopy confirms actual RBCs alongside bilirubin, this unusual combination requires:

• Assess for dysmorphic RBCs or RBC casts indicating glomerular disease - tea-colored urine with proteinuria >2+ suggests glomerulonephritis 1
• In children, obtain detailed history for sickle cell disease, hemophilia, familial renal disease, and hearing loss (Alport syndrome) 1
• Check for infection - presence of white cells and microorganisms indicates UTI, which can rarely cause hemolysis in neonates with α-hemolytic bacteria 1, 4

Imaging Approach for True Hematuria

• Renal ultrasound is the first-line imaging to assess kidney size, echogenicity, and structural abnormalities 1
• CT urography is NOT appropriate for isolated nonpainful, nontraumatic hematuria in children 1
• In adults with gross hematuria, CT urography is preferred, but the presence of bilirubinuria makes hemolysis more likely than urologic pathology 5

Common Pitfalls to Avoid

• Do not assume dipstick-positive "blood" equals true hematuria - always confirm with microscopy to distinguish RBCs from hemoglobin/myoglobin 3, 2
• Do not delay hemolysis workup if both blood and bilirubin are present on dipstick - this combination strongly suggests intravascular hemolysis 1, 2
• In children with isolated microscopic hematuria without proteinuria, no imaging is indicated as clinically significant renal disease is unlikely 1
• Do not attribute findings to exercise or medications without excluding serious hemolytic conditions, especially if acute kidney injury is present 2