What are the management and treatment options for a patient who develops aplastic anemia after taking a single dose of naproxen?

Management of Naproxen-Induced Aplastic Anemia

Immediately discontinue naproxen and initiate supportive care with transfusion support, followed by immunosuppressive therapy or hematopoietic stem cell transplantation depending on disease severity, patient age, and donor availability. 1, 2

Immediate Actions

Stop the offending drug immediately – naproxen must be permanently discontinued as the causative agent of drug-induced aplastic anemia. 3, 4

• Obtain complete blood count with differential, reticulocyte count, and peripheral smear to assess severity of pancytopenia 1
• Perform bone marrow biopsy and aspirate to confirm diagnosis and rule out hypocellular myelodysplastic syndrome or acute leukemia 1
• Initiate supportive care with irradiated and filtered blood products to prevent transfusion-associated complications 2
• Monitor for infection with temperature checks at least twice daily, and initiate broad-spectrum intravenous antibiotics immediately if fever >38.2°C develops 3

Severity Grading and Risk Stratification

Classify disease severity based on absolute neutrophil count (ANC), platelet count, and reticulocyte count to determine treatment approach. 1

• Severe aplastic anemia is defined by bone marrow cellularity <25% with at least two of: ANC <0.5 × 10⁹/L, platelets <20 × 10⁹/L, or reticulocytes <20 × 10⁹/L 1, 5
• Perform HLA typing immediately for all patients to identify potential matched sibling donors 2
• Obtain cytogenetic analysis and flow cytometry to distinguish aplastic anemia from hypocellular MDS 1

Definitive Treatment Algorithm

For Young Patients (<40 years) with Severe Disease:

Hematopoietic stem cell transplantation is first-line therapy if an HLA-identical sibling donor is available, with survival rates exceeding 90% in young patients. 1, 6

• Use bone marrow as the stem cell source with ATG-containing conditioning regimen 6
• Matched unrelated donor transplantation is increasingly considered first-line for very young patients lacking sibling donors 6

For Patients Without Matched Donors or Age >40 Years:

Immunosuppressive therapy with horse antithymocyte globulin (ATG) plus cyclosporine is the standard regimen, achieving response rates of 60-70%. 1, 2, 6

• Horse ATG demonstrates significantly higher response rates and overall survival compared to rabbit ATG 6
• Continue cyclosporine for prolonged periods as maintenance therapy 2, 5

For Treatment-Naïve Severe Disease (Emerging Approach):

Combine eltrombopag with horse ATG plus cyclosporine starting from day 1 and continuing for 6 months, yielding complete response rates of 58% and overall response rates of 94% at 6 months. 2

For Refractory Disease:

Add eltrombopag to supportive care for patients refractory to initial immunosuppressive therapy, with response rates of 40-48%. 2, 6

Monitoring During Treatment

• Obtain complete blood count with differential weekly during initial treatment 1
• Monitor for improvement in blood counts and reduction in transfusion requirements 1
• For patients on eltrombopag, monitor liver function tests regularly as hepatotoxicity (increased transaminases) occurs in 13% of patients and represents the only dose-limiting toxicity 2
• Monitor for thromboembolism as thrombosis is a serious adverse event with eltrombopag therapy 2
• Continue monitoring until sustained normalization of counts is documented 3

Critical Pitfalls to Avoid

Do not delay treatment initiation while awaiting complete diagnostic workup – this can be harmful in severe disease. 1

• Never reintroduce naproxen or other NSAIDs – drug-induced aplastic anemia has a dose-independent idiosyncratic mechanism with high mortality risk upon re-exposure 4
• Distinguish between aplastic anemia and hypocellular MDS or leukemia, as inappropriate treatment can worsen outcomes 1
• If ANC drops below 1.0 × 10⁹/L, hospitalize immediately for infection surveillance and consider G-CSF, which improves neutropenia in 60-75% of cases 3
• Maintain platelet transfusions to prevent bleeding complications 1
• Be aware that rebound thrombocytopenia may occur upon eltrombopag discontinuation – in robust responders, abrupt discontinuation is described rather than gradual tapering 2

Prognosis

The prognosis of drug-induced aplastic anemia is similar to idiopathic aplastic anemia, with patients responding to bone marrow transplantation or immunosuppressive therapy in comparable fashion. 4 However, idiosyncratic drug-induced aplastic anemia carries high mortality without appropriate treatment. 4