Sodium Valproate-Associated Thrombocytopenia in Antiepileptic Drug Polypharmacy: A Case Report and Review of the Literature.

BACKGROUND Drug-induced thrombocytopenia (DITP) is a potentially life-threatening adverse drug reaction, representing approximately 20% to 25% of acquired thrombocytopenia cases. Sodium valproate (VPA) and levetiracetam are widely used antiepileptic drugs; reported incidences of VPA-associated thrombocytopenia range from 5% to 32%, depending on serum concentrations. Although both agents are frequently combined in the management of refractory epilepsy, limited information is available regarding their synergistic hematological risks. CASE REPORT We encountered a case of DITP in a 31-year-old man with an epileptic mental disorder who was receiving VPA and levetiracetam in combination. The patient had previously received either VPA or levetiracetam as monotherapy without thrombocytopenia onset. However, after initiation of combination therapy, the patient developed progressive thrombocytopenia, with a nadir platelet count of 47×10⁹/L. Laboratory testing revealed a serum VPA concentration of 112.4 μg/mL, exceeding the therapeutic range (50-100 μg/mL). After VPA discontinuation, the platelet count gradually recovered to 93×10⁹/L, approaching normal levels. CONCLUSIONS This case highlights a potential pharmacokinetic interaction between levetiracetam and VPA, suggesting that levetiracetam can influence VPA metabolism. It underscores the importance of close therapeutic drug monitoring of VPA concentrations during combination therapy and emphasizes the need for further investigation into metabolic interactions between novel and conventional antiepileptic agents.