Rapid Leukocyte Reduction after a Re-challenge with Balproate in a Patient with Neutropenia and Thrombocytopenia: A Case Report

重新使用valproate治療曾因valproate引起的白血球和血小板低下病人造成白血球快速減少：案例報告

林峯立(Feng-Li Lin)；詹宏裕(Hung-Yu Chan)

Neutropenia ； Thrombocytopenia ； Hematologic abnormality ； Valproate ； Re-challenge ； 白血球低下 ； 血小板低下 ； 血液學異常 ； valproate ； 重新使用

醫學與健康期刊

7卷2期（2018 / 09 / 01）

123 - 129

英文

Valproate has been associated with a variety of hematologic abnormalities, such as neutropenia, thrombocytopenia and pancytopenia. Although it is less common for thrombocytopenia to accompany neutropenia, their co-occurrence is potentially more serious than the occurrence of thrombocytopenia alone. Herein we reported a patient who had valproaterelated neutropenia and thrombocytopenia and experienced rapid leukocyte reduction after valproate was reintroduced. A 33-year-old female patient with Turner syndrome and schizophrenia was started on continuous valproate for mood symptoms, poor impulse control and seizure prevention from February 7th, 2011 to February 6th, 2014 in a psychiatric chronic ward. Her psychotropic medications were tapered down initially due to her unstable physical condition arising from pneumonia and then brought back up her ordinary dose after her pneumonia had stabilized. The patient appeared neutropenia starting on 26th day and then also thrombocytopenic on the 33rd day of the readmission to acute ward. We discontinued valproate, and the patient's neutropenia and thrombocytopenia subsided within a week. We reintroduced valproate (1000 mg/day) one week later, and the patient developed a drop in leukocytes. We once again discontinued valproate, and nine days later her leukocyte counts rose. Although previous case studies have reported that reintroducing valproate in patients with a history of drug-induced hematologic abnormalities may be safe, this did not prove to true in our patient. Valproate should be reintroduced with caution and careful monitoring of patient's hematologic profile, especially in a patient with previous valproate-induced side effects.

使用valproate藥物造成的血液學副作用包含白血球低下、血小板低下及全血球低下。血小板低下合併白血球低下相對少見，且危險性較單獨發生血小板低下高。本文報告一位重新使用valproate治療，曾因valproate引起的白血球和血小板低下的病人，造成白血球快速減少。一位33歲女性，被診斷為透納氏症及思覺失調症。在精神科病房中使用valproate治療衝動控制不佳、情緒起伏大及控制癲癇。由於肺炎，她停止valproate使用，但在肺炎穩定後又再度服用valproate。再度服用後第26天發現白血球低下，第33天有血小板低下。白血球低下及血小板低下在停止valproate一週內緩解。我們在一週內將valproate加回1000mg/d，病人的白血球再度下降。立即停用valproate後9天，病人的白血球回升。過去曾有報告指出在曾因valproate引起的白血球低下病人身上重新使用valproate是安全的，但此個案報告顯示不同的結果。醫師在重新使用valproate時，需要留心血液學的相關副作用，尤其是曾出現valproate引起的白血球低下病史的病人。

1. Acharya, S1,Bussel, JB(2000).Hematologic toxicity of sodium valproate.J Pediatr Hematol Oncol,22,62-5.
2. Barr, RD,Copeland, SA,Stockwell, ML,Morris, N,Kelton, JC(1982).Valproic acid and immune thrombocytopenia.Arch Dis Child,57,681-4.
3. Bhatt, V,Saleem, A(2004).Review: Drug-Induced Neutropenia- Pathophysiology, Clinical Features, and Management.Ann Clin Lab Sci,34,131-7.
4. Daniel, D,Storch, MD(2000).Severe leukopenia with valproate.J Am Acad Child Adolesc Psychiatry,39,1208-9.
5. Hung, WC,Hsieh, MH(2012).Neutropenia associated with the comedication of quetiapine and valproate in 2 elderly patients.J Clin Psychopharmacol,32,416-7.
6. Kohli, U,Gulati, S(2006).Valproate induced isolated neutropenia.Indian J Pediatr,73,844.
7. Pantelis, C,Adesanya, A(2001).Increased risk of neutropenia and agranucytosis with sodium valproate used adjunctively with clozapine.Aust N Z J Psychiatry,35,544-5.
8. Stewart, JT(2011).Successful reintroduction of valproic acid after the occurrence of pancytopenia.Am J Geriatr Pharmacother,9,351-3.
9. Stoner, SC,Deal, E,Lurk, JT(2008).Delayed onset neutropenia with divalproex sodium.Ann Pharmacother,42,1507-10.