G-CSF治療Ticlopidine造成顆粒性白血球缺乏：一病例報告

Granulocyte Colony Stimulating Factor for Agranulocytosis Secondary to Ticlopidine--Report of a Case

嗜中性白血球減少是血液疾病的一種，嚴重的嗜中性白血球減少通常是藥物所造成的。雖然藥物引起嗜中性白血球減少的發生率並不高，但因有致命之虞，因此使用這類藥品時需嚴密監測，若發生嗜中性白血球減少則必須作適當處理並加以治療。成大醫院曾在住院病人中發現一例疑似抗血小板凝集藥物Ticlopidine所引發的顆粒性白血球缺乏，此病人為不穩定心絞痛患者，因再次胸痛入院，住院期間原使用Aspirin治療冠狀動脈疾病，後來懷疑有胃腸出血徵兆，而改用Ticlopidine，38天後White blood cell (WBC)降至2.1 X 10的9次方/L，Absolute neutrophil count (ANC)為 0.168 X 10的9次方/L，Hemoglobin (Hb)為 9.7g/dl，Platelet(PLT)217 X 10的9次方/L，併發感染發燒，懷疑是Tidopidine造成的顆粒性白血球缺乏，及時停用Ticlopidine，並給于G-CSF與抗生素治療，一星期後WBC升到15.4 X 10的9次方/L、 ANC 8.9 X 10的9次方/L，病情也逐漸好轉。本文乃針對抗血小板凝集藥物Ticlopidine引起嗜中性白血球減少的機轉原因與處理方式加以探討，並回顧國內外相關文獻報告，期待藉由此病例的研討能讓醫師、藥師警覺到Ticlopidine臨床使用上之適應症與安全性，需依規定作好藥物監測工作；進而了解臨床藥師如何協助醫師查證藥物所導致的顆粒性白血球缺乏，及時建議停藥，並作適當處置，得以避免病情惡化。

Neutropenia is a blood disease. Severe neutropenia is most often drug-induced. Though the incidence is low, it can be fatal. Therefore, the use of neutropenia-inducing drugs needs to be closely monitored. Proper care and treatment is essential should neutropenia occur. We report a 70-years-old female patient with agranulocytosis induced by the antiplatelet agent, ticlopidine in National Cheng Kung University Hospital. This patient, who had unstable angina, was hospitalized for recurrent chest pain. During hospitalization, aspirin was initially used to treat coronary artery disease, and was later changed to ticlopidine because of suspicious gastrointestinal bleeding symptom. After 38 days of treatment, the patient’s white blood cell count (WBC) lowered to 2.1 X 1000000000/L. with absolute neutrophil count (ANC) 0.168 X 1000000000/L, hemoglobin 9.7g/dl and platelet count 217 X 1000000000/L. The patient suffered from complicated infection and fever, which was suspected to be caused by ticlopidine-induced agranulocytosis. Ticlopidine was immediately discontinued and granulocyte colony stimulating factor and antibiotics were given. One week later, the patient’s WBC increased to 15.4 X 1000000000/L, ANC to 8.9 X lO00000000/L, and the patient’s condition improved. This article focuses on the mechanism and management of neutropenia induced by the antiplatelet agent, ticlopidine. Relevant reports and articles are also reviewed. We hope that through this case discussion, both physicians and pharmacists will become alert to the clinical indications and safety of ticlopidine, as well as to the importance of drug monitoring. We also address how clinical pharmacists can help in detecting drug-induced agranulocytosis and provide appropriate suggestions when necessary.