Johnston Jackie P, Nerenberg Steven F
Department of Pharmacy, St. Joseph's University Medical Center, Paterson, NJ, USA.
Pharmacy Practice and Administration, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ, USA.
Am J Case Rep. 2020 Dec 30;21:e927830. doi: 10.12659/AJCR.927830.
BACKGROUND Valproic acid is utilized for the management of various disease states, but coagulation changes, such as thrombocytopenia, can limit use. Valproic acid is a highly protein-bound drug. Serum levels of 50-100 mcg/mL are considered therapeutic, with minimal risk of toxicity when maintained within the recommended therapeutic index. We present a case of valproic acid-induced thrombocytopenia associated with spontaneous systemic bleeding. CASE REPORT A 57-year-old woman with history of generalized anxiety disorder and choreiform movements presented to the Emergency Department with 1 day of oral and vaginal bleeding. The patient had been started on valproic acid for choreiform movements 3 weeks prior. On physical exam, the patient was noted to have atraumatic contusions and ecchymosis. A CT head revealed left temporal frontal subdural hematoma (4.5 mm), acute subdural hematoma along the posterior aspect of the interhemispheric falx (5 mm), mass effect on the right lateral ventricle, and an approximately 3 mm right-to-left midline shift. Laboratory testing was notable for platelets 4000/μL, hemoglobin 7.3 g/dL, hematocrit 23.1%, fibrinogen 467 mg/dL, and valproic acid random level 26.3 μg/mL. Thromboelastography releveled normal values except for a decreased maximum amplitude of 33.4 mm. CONCLUSIONS Although the clinical relevance is still debated, few case reports of significant bleeding related to valproic acid-induced thrombocytopenia exist. To the best of our knowledge, this is the first case report of spontaneous systemic bleeding due to valproic acid-induced thrombocytopenia in the setting of normal fibrinogen levels. Furthermore, this report demonstrates the potential risk of thrombocytopenia with subtherapeutic VPA levels.
丙戊酸用于多种疾病状态的治疗，但凝血变化，如血小板减少，可能会限制其使用。丙戊酸是一种高度蛋白结合药物。血清水平为50 - 100 mcg/mL被认为具有治疗作用，当维持在推荐治疗指数范围内时，毒性风险最小。我们报告一例丙戊酸诱导的血小板减少症并伴有自发性全身出血的病例。病例报告：一名57岁女性，有广泛性焦虑症和舞蹈样动作病史，因口腔和阴道出血1天就诊于急诊科。该患者在3周前开始使用丙戊酸治疗舞蹈样动作。体格检查发现患者有非创伤性瘀斑和瘀点。头颅CT显示左侧颞额叶硬膜下血肿（4.5 mm），大脑镰后部急性硬膜下血肿（5 mm），对右侧脑室有占位效应，以及约3 mm的右向左中线移位。实验室检查结果显示血小板计数为4000/μL，血红蛋白7.3 g/dL，血细胞比容23.1%，纤维蛋白原467 mg/dL，丙戊酸随机水平26.3 μg/mL。血栓弹力图除最大振幅降至33.4 mm外，其余指标恢复正常。结论：尽管临床相关性仍存在争议，但与丙戊酸诱导的血小板减少症相关的严重出血的病例报告很少。据我们所知，这是第一例在纤维蛋白原水平正常情况下因丙戊酸诱导的血小板减少症导致自发性全身出血的病例报告。此外，本报告显示了亚治疗剂量丙戊酸水平时发生血小板减少症的潜在风险。
