A 12-year-old boy is brought to the office for evaluation of intermittent dark urine and exertional fatigue for 2 weeks. He has had no trauma, fever, muscle aches, dysuria, or urinary frequency or urgency. The patient underwent aortic valve replacement with a mechanical valve for bicuspid aortic regurgitation a year ago, and he takes daily warfarin. Temperature is 37.5 C (99.5 F), blood pressure is 110/64 mm Hg, pulse is 98/min, and respirations are 16/min. Cardiac examination reveals a regular rate and rhythm with crisp mechanical heart valve clicks. Abdomen is soft and nontender. There is no edema. Urinalysis reveals the following:
| Specific gravity | 1.020 |
| Protein | none |
| Blood | 3+ |
| Leukocytes | negative |
| Bacteria | none |
| White blood cells | 1-2/hpf |
| Red blood cells | 1-2/hpf |
| Casts | none |
| Crystals | none |
What is the best next step in management?
Show Explanatory Sources
This patient with dark urine has heme positivity on urine dipstick but very few urinary red blood cells (RBCs), findings that occur with myoglobinuria or hemoglobinuria. In the absence of muscle aches (eg, rhabdomyolysis), this patient with a mechanical aortic valve most likely has hemoglobinuria, a condition in which free hemoglobin is present in the urine. Increased turbulence through the prosthetic valve causes shearing forces on the RBCs, which can lead to intravascular hemolysis and release of free hemoglobin.
Hemoglobinuria occurs when free hemoglobin exceeds both the saturation of serum haptoglobin and the resorptive capacity of the proximal tubule. The result is urine that is red (ie, hemoglobin pigment) or brown (ie, methemoglobin pigment) with detection of heme (ie, positive blood) on urine dipstick but with only 0-2 RBCs in the urine, which is normal and considered negative, in contrast to hematuria (≥3 RBCs/hpf).
The best next step in evaluation of this pediatric patient with suspected hemolysis is a complete blood count to confirm the presence of and assess the severity of anemia, which is likely the cause of this patient's exertional fatigue. Additional findings of mechanical intravascular hemolysis include low haptoglobin, elevated lactate dehydrogenase, increased reticulocytes, and schistocytes on peripheral smear.
(Choice A) The risk of bleeding is increased with anticoagulant therapy, such as warfarin, a vitamin K antagonist. However, true hematuria with elevated RBCs in the urine would be expected.
(Choices C, D, and F) Evaluation of hematuria can include renal and bladder ultrasound for signs of nephrolithiasis (eg, flank pain, urinary crystals), serum complement levels for signs of glomerulonephritis (eg, hypertension, proteinuria, urinary RBC casts), and urine culture for signs of infection (eg, dysuria, pyuria). However, this patient's urinalysis is not consistent with hematuria.
(Choice E) Two sets of blood cultures from separate venipuncture sites are indicated for suspected infective endocarditis (IE). Although a prosthetic valve increases the risk of IE, fever and/or new murmur are classic signs that are not seen in this patient. In addition, hematuria due to IE-associated acute kidney injury would cause ≥3 RBCs and often protein in the urine.
Educational objective:
Hemoglobinuria, in which free hemoglobin is present in the urine, should be suspected in a patient with risk factors for intravascular hemolysis (eg, mechanical valve) and red/brown urine that is heme positive but negative for red blood cells. The first step in evaluation of hemolytic anemia is a complete blood count.