丙戊酸（valproic acid）治療後高血氨病人CRP和血小板之相關性分析及臨床意義

Analysis of the Clinical Significance of CRP and Platelet in Patients with Hyperammonemia after Treatment with Valproic Acid and its Clinical Application

丙戊酸（valproic acid, VPA）是一個廣效性的抗癲癇藥物，可單獨使用或與其他抗癲癇藥物併用於治療失神性發作（absence seizure）。有研究指出丙戊酸劑量增加1mg會使高血氨症（hyperammonemia, AMM）的風險增加0.1%，但也有文獻表明丙戊酸可以預防炎症和細胞凋亡，可有效控制癲癇發作。Ｃ反應性蛋白試驗（C-Reactive protein, CRP）是炎症標誌物，因丙戊酸的抗炎特性，想探討臨床經丙戊酸治療的病人，是否有通過抗炎，抗凋亡保護大腦免受損傷，況且臨床上經丙戊酸治療的癲癇患者，其對高血氨症還尚未有充分的研究。所以收集215位經丙戊酸治療的病患，分組後使用回歸統計比對其丙戊酸、CRP和血氨之統計分析，分析後發現大部分年長者和慢性精神科病房裡長期使用丙戊酸治療的病患，醫師再給予丙戊酸治療，可使病患體內丙戊酸濃度升高，達到毒性劑量（toxic level: >100μg/mL），進而抑制腦部炎症保護大腦免受損傷使CRP降低，但因病患本身長期服用丙戊酸，容易併發高血氨；臨床上給予青少年急性丙戊酸治療，其體內丙戊酸濃度升高達到毒性劑量會抑制腦部炎症保護大腦免受損傷，CRP會降低但並未出現高血氨。經由此研究結果，醫師對年紀大、肝功能異常病患施以丙戊酸治療須保持警惕，並常規監測血氨濃度，若發現病患血氨濃度偏高且一般治療無效，可考慮以其他治療藥物來替代丙戊酸。未來希望能更詳細分析臨床上男女患者使用丙戊酸有毒性劑量治療下誘導血小板減少症的臨床意義。

Valproic acid is a broad-spectrum antiepileptic drug that can be used alone or in combination with other antiepileptic medications to treat absence seizures. It indicated that an increase of 1mg in valproic acid dosage can result in a 0.1% higher risk of hyperammonemia in our research. However, valproic acid’s anti-inflammatory and anti-apoptotic properties could effectively control seizures. Given its anti-inflammatory attributes, the investigation explores if valproic acid can shield the brain from damage through CRP.
This study addressed a research gap by examining 215 valproic acid-treated patients. Classification was based on valproic acid levels, CRP, and blood ammonia. The results unravel significant patterns.
In older patients with chronic conditions, valproic acid administration (toxic level: >100 μg/mL) elevated valproic acid levels, reducing brain inflammation and CRP. However, prolonged valproic acid use posed a hyperammonemia risk. Conversely, acute valproic acid treatment in adolescents yielded reduced CRP without hyperammonemia despite elevated valproic acid.
In patients of advanced age or with compromised liver function, cautious valproic acid administration is advisable, alongside regular blood ammonia monitoring. Alternatives should be considered if elevated levels surface and standard treatments prove ineffective.
Future research aims to delve deeper into the clinical significance of valproic acid-induced platelet reduction, particularly across gender lines.