What is the best course of treatment for a 19-year-old patient with a history of pulmonary embolism and superficial thrombophlebitis, currently on Eliquis (apixaban), presenting with symptoms of urinary frequency, urgency, hematuria, and dysuria?

Treatment of Acute Cystitis in a Young Patient on Apixaban

Treat this patient with standard short-course antibiotic therapy for uncomplicated cystitis while continuing apixaban, as the hematuria is most likely secondary to the urinary tract infection rather than anticoagulation alone. 1

Clinical Reasoning

This 19-year-old presents with classic symptoms of uncomplicated cystitis: dysuria, frequency, urgency, and hematuria occurring over 1 day. 1 The European Association of Urology guidelines define uncomplicated cystitis as acute cystitis in patients without relevant anatomic or functional urinary tract abnormalities and no comorbidities—though this patient's anticoagulation status requires consideration. 1

Key Diagnostic Considerations

• Diagnosis can be made clinically based on the focused history of lower urinary tract symptoms (dysuria, frequency, urgency) without requiring urine culture in typical presentations. 1
• Urine culture is NOT routinely indicated for uncomplicated cystitis with typical symptoms, as it adds cost without improving diagnostic accuracy. 1
• However, obtain a urine culture in this case because the patient is on anticoagulation and has hematuria, making this presentation somewhat atypical and warranting documentation of the pathogen. 1

Hematuria in the Context of Anticoagulation

The critical question is whether the hematuria represents:

1. A complication of anticoagulation requiring intervention
2. A symptom of the UTI itself

The evidence strongly suggests the UTI is the primary driver:

• Hematuria is a common symptom of uncomplicated cystitis itself, occurring in otherwise healthy patients not on anticoagulation. 1, 2
• While apixaban can cause hematuria, research shows it is actually safer than other anticoagulants (warfarin, rivaroxaban) in terms of hematuria risk. 3
• Studies demonstrate that anticoagulant-associated hematuria is frequently precipitated by underlying genitourinary pathology (30% of cases), with UTI being a common trigger. 4
• Most anticoagulant-related hematuria is mild to moderate and resolves with treatment of the underlying condition without needing to stop anticoagulation. 5

Antibiotic Selection and Duration

Recommend 3-day antibiotic therapy as the optimal duration for uncomplicated cystitis:

• Three-day therapy is superior to single-dose treatment, eradicating infection in virtually all patients while decreasing relapse rates. 2
• First-line options include nitrofurantoin, trimethoprim-sulfamethoxazole, or fosfomycin, chosen based on local resistance patterns and patient tolerance. 1
• Avoid fluoroquinolones as first-line due to ecological concerns unless other options are contraindicated. 1

Management of Apixaban

Continue apixaban without interruption:

• This patient has a history of pulmonary embolism, placing them at high risk for recurrent thromboembolism if anticoagulation is interrupted. 6
• The ESC guidelines emphasize that patients with PE require >3 months of anticoagulation and face lifelong recurrence risk. 1
• Stopping anticoagulation for mild-to-moderate hematuria in the setting of acute infection is not recommended when the hematuria is likely secondary to the UTI. 5
• If hematuria were severe enough to require holding anticoagulation, it should be held for <2 days and restarted promptly. 5

Critical Pitfalls to Avoid

• Do NOT use bridging anticoagulation with heparin if apixaban needs to be temporarily held, as this increases bleeding risk without benefit. 6
• Do NOT routinely stop anticoagulation for hematuria that is likely UTI-related, as the thrombotic risk outweighs the bleeding risk in this young patient with recent PE. 6, 5
• Do NOT obtain post-treatment urine cultures if symptoms resolve, as this is not indicated for asymptomatic patients. 1

Follow-Up Strategy

• Reassess in 2-3 days to confirm symptom resolution, particularly the hematuria. 1
• If symptoms persist or recur within 2 weeks, obtain urine culture with susceptibility testing and consider 7-day therapy with an alternative agent. 1
• Monitor renal function after treatment, as impairment increases both bleeding and thrombotic risks with DOACs like apixaban. 6
• If hematuria persists after UTI treatment resolves, then consider urological evaluation for other pathology, though this is unlikely in a 19-year-old. 4

Special Consideration: Underlying Thrombophilia

The combination of PE and superficial thrombophlebitis at age 19 suggests possible underlying thrombophilia. Ensure this patient:

• Has been evaluated for inherited or acquired thrombophilia
• Understands the need for long-term or indefinite anticoagulation given unprovoked VTE at young age 1
• Is scheduled for 3-6 month re-evaluation after the PE event per ESC guidelines 1, 7