|
Valproic acid and thrombocytopenia: cross-sectional
study
CH Ko, CK Kong, PWT Tse
Developmental Disabilities Unit, Department of Paediatrics, Caritas
Medical Centre, 111 Wing Hong Street, Shamshuipo, Hong Kong
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.
Hong Kong Med J 2001;7:15-21
Key words: Anticonvulsants/adverse effects; Thrombocytopenia/chemically
induced; Valproic acid/adverse effects
|
