OBJECTIVES. To investigate the relationship between platelet count and serum valproic acid level, age, duration of valproic acid therapy, and polytherapy, and to determine the clinical significance of thrombocytopenia associated with high-dosage valproic acid therapy.

DESIGN. Cross-sectional study.

SETTING. Residential unit for neurologically impaired children and paediatric out-patient clinic, Hong Kong.

PATIENTS. Ninety-six neurologically impaired children who were treated with valproic acid between 1 July 1991 to 3 June 1999. The comparison group consisted of 48 children receiving antiepileptic drugs other than valproic acid.

INTERVENTION. Low- or high-dosage valproic acid, using the threshold value of 40 mg/kg/d.

MAIN OUTCOME MEASURES. Platelet count and liver function, duration of valproic acid treatment, dosage, and trough serum valproic acid concentration.

RESULTS. Seventeen (17.7%) patients in the treatment group developed thrombocytopenia, compared with two (4.2%) in the comparison group (P<0.05). The platelet count was negatively correlated to serum valproic acid level and age, and positively correlated to polytherapy. The duration of valproic acid treatment was not a confounding factor in the age-related decrease in platelet count. Children with a trough level of >450 micromol/L or a daily dose of >40 mg/kg were more likely to develop thrombocytopenia. Thrombocytopenia was mild in most cases.

CONCLUSIONS. A trough valproic acid level of >450 micromol/L or a daily dose of >40 mg/kg should alert the clinician to the risk of developing thrombocytopenia. The risk is further increased for older children. The platelet count should be monitored for patients receiving a high concentration of valproic acid who are also receiving drugs that would affect homeostasis, or who are undergoing surgical procedures.

Key words: Anticonvulsants/adverse effects; Thrombocytopenia/chemically induced; Valproic acid/adverse effects

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