From the Guidelines
The development of anemia with elevated reticulocytes in a neonate with systemic HSV on acyclovir is most likely due to acyclovir-induced hemolytic anemia, which requires prompt management. The immediate recommendation is to obtain a complete blood count with reticulocyte count, peripheral blood smear, direct Coombs test, and serum acyclovir levels. Consider reducing the acyclovir dose if possible while maintaining therapeutic efficacy (typically from 20 mg/kg/dose three times daily to a lower dose) or switching to an alternative antiviral agent if severe hemolysis is present, as the current dose of 20 mg/kg/dose three times daily is recommended for neonatal HSV disease treatment 1. Ensure adequate hydration with IV fluids to prevent acyclovir crystallization in the kidneys. Monitor hemoglobin levels daily until stabilized. This hemolytic anemia occurs because acyclovir can cause immune-mediated destruction of red blood cells or direct toxic effects on erythrocytes, particularly in neonates with immature renal function leading to drug accumulation. The elevated reticulocyte count indicates the bone marrow is responding appropriately to the hemolysis. If anemia is severe (hemoglobin <8 g/dL) or the neonate is symptomatic, a blood transfusion may be necessary. Once the HSV infection is adequately treated, consider transitioning to oral acyclovir suppressive therapy to prevent recurrence while avoiding further hemolysis. Key considerations include:
- Monitoring for signs of hemolysis and adjusting the acyclovir dose accordingly
- Maintaining adequate hydration to prevent acyclovir crystallization
- Regularly assessing hemoglobin levels and considering blood transfusion if necessary
- Transitioning to oral acyclovir suppressive therapy after adequate treatment of the HSV infection, as recommended for neonatal HSV disease treatment 1.
From the FDA Drug Label
WARNING Acyclovir tablets is intended for oral ingestion only. Renal failure, in some cases resulting in death, has been observed with acyclovir therapy (see ADVERSE REACTIONS: Observed During Clinical Practice and OVERDOSAGE). Thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS), which has resulted in death, has occurred in immunocompromised patients receiving acyclovir therapy. The development of new anemia with elevated reticulocytes in a neonate with systemic HSV on acyclovir may be related to hemolytic uremic syndrome (HUS), a known adverse reaction of acyclovir therapy, especially in immunocompromised patients 2.
- Key points:
- Acyclovir therapy has been associated with HUS.
- HUS can cause anemia with elevated reticulocytes.
- Neonates with systemic HSV are considered immunocompromised. However, the FDA drug label does not directly answer whether acyclovir causes new anemia with elevated reticulocytes in neonates with systemic HSV.
From the Research
New Anemia with Elevated Reticulocytes in Neonate with Systemic HSV on Acyclovir
- The provided studies do not directly address the issue of new anemia with elevated reticulocytes in a neonate with systemic HSV on acyclovir.
- However, the studies provide information on the safety and efficacy of acyclovir in treating neonatal HSV infections 3, 4, 5, 6.
- Acyclovir is a selective antiherpes agent that is effective in treating HSV infections, but it can cause adverse effects such as renal dysfunction and nephrotoxicity 5, 7.
- The study by 3 found that clinical and laboratory adverse events (AEs) were common among infants with neonatal HSV treated with high-dose acyclovir, but severe AEs were rare.
- Another study by 4 discussed the management of HSV infections in neonates, including the use of parenteral acyclovir, but did not mention anemia or elevated reticulocytes as a specific adverse effect.
- The study by 7 reported cases of acyclovir-induced renal failure, which may be relevant to the development of anemia in neonates, but the exact mechanism is not clear.
- Overall, while the studies provide some information on the safety and efficacy of acyclovir in treating neonatal HSV infections, they do not directly address the issue of new anemia with elevated reticulocytes in a neonate with systemic HSV on acyclovir 3, 4, 5, 6, 7.