C H Ko1, C K Kong, P W Tse. 1. Developmental Disabilities Unit, Department of Paediatrics, Caritas Medical Centre, 111 Wing Hong Street, Shamshuipo, Hong Kong.
Abstract
OBJECTIVE: 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.
OBJECTIVE: 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.
Authors: Donna C Davidson; Michael P Hirschman; Sherry L Spinelli; Craig N Morrell; Giovanni Schifitto; Richard P Phipps; Sanjay B Maggirwar Journal: J Immunol Date: 2010-11-29 Impact factor: 5.422
Authors: Negar Golchin; Hannah Johnson; Paul M Bakaki; Neal Dawson; Elia M Pestana Knight; Sharon B Meropol; Rujia Liu; James A Feinstein; Shari D Bolen; Lawrence C Kleinman; Alexis Horace Journal: Drugs Ther Perspect Date: 2019-07-12