Abstracts

Rationale: The mechanism of AED side effects is usually divided into two types, depending on idiosyncrasy and dose-dependence. Severe cytopenia and liver dysfunction are reported as well-known but uncommon AED side effects depending on idiosyncrasy. However, in clinical practice we often find haematological and biochemical change caused by AED more than reported. Several studies reported haematological difference by AED not depending on idiosyncrasy, nevertheless those studies included patients with multiple AED therapy. Therefore, we investigated how AED monotherapy affects haematological and biochemical parameters. Methods: We retrospectively recruited 478 patients untreated with AED. We excluded patients from analysis in accordance with the following exclusion criteria: (1) patients with malignant cancer, trauma, cerebrovascular disease, liver or renal dysfunction (2) discontinued AED or switched AEDs within 2 weeks (3) no blood sample before and after 3 months from AED initiation (4) others such as pregnancy. Sixty-seven of 478 (14%) patients with CBZ (carbamazepine: n=28), VPA (sodium valproate: n=19) or LEV (levetiracetam: n=20) were selected for further analysis. We examined haematological and biochemical parameters and AED plasma concentration of patients medicated AED monotherapy within 3 months before and from 2 weeks to 3 months after AED commencement. We compared the haematological and biochemical parameters between pre- and post-medication and assessed correlations between the rate of parameters (post-/pre-medication) and AED plasma concentration. Results: In patients with CBZ, WBC (white blood cell) count was significantly lower at post-medication (pre- 6.2±1.9×10³/µL, post- 5.3±1.6×10³/µL, P3/µL in 18 patients. The rate of WBC change had a tendency to correlate with plasma concentration at post-medication, but not significant (the Pearson’s correlation coefficient, R²=0.38, P=0.056). GGT (gamma-glutamyltransferase) and ALP (alkaline phosphatase) count was significantly higher at post-medication (GGT: pre- 28.4±17.9 U/L, post- 63.6±42.5 U/L, P4/µL, post- 20.7±6.3×10⁴/µL, P=0.006). The rate of Plt change did not correlate with VPA plasma concentration. In patients with LEV, there was no significant difference in all parameters between pre- and post-medication. Conclusions: The reduction of WBC caused by CBZ were observed in 18/26 patients. It was revealed that GGT and ALP was increased at high frequency. We revealed tendency that the higher the CBZ concentration, the lower WBC count, therefore it is possible that reduction of WBC is induced by dose-dependence. We should watch carefully haematological and biochemical parameters in patients with AED especially in the case of high AED dosage. Funding: None