达沙替尼致反复发作部分可逆性肺动脉高压一例并文献复习

Repeated partially reversible pulmonary arterial hypertension related to dasatinib：a case report and literature review

目的 探讨达沙替尼导致肺动脉高压的临床特点和转归.方法 回顾分析1例达沙替尼治疗过程中出现肺动脉高压患者的临床特点.以“达沙替尼”、“肺动脉高压”为关键词在万方数据库和中国期刊全文数据库进行检索,以“dasatinib,pulmonary arterial hypertension”为关键词在Pubmed 数据库进行检索.结果 患者男,55岁,因诊断“慢性粒细胞性白血病”应用“达沙替尼100 mg/d”治疗,用药36个月后出现胸闷、乏力及全身水肿,纽约心功能分级Ⅳ级,超声心动图示右侧房室内径均扩大,室壁增厚,右心室收缩功能减低,主肺动脉及左右分支增宽,估测肺动脉收缩压（sPAP）115 mmHg（1 mmHg =0.133 kPa）,伴心包积液,左侧房室内径正常,左心室收缩功能正常.胸部B超提示双侧胸腔积液.此后患者自行停药并恢复用药5次,停药后症状均好转,前3次停药后超声心动图sPAP可降至37 ～ 82 mmHg,心包及胸腔积液消失,第4次停药后1年肺动脉压力维持80 mmHg,再次自行服药.因患者拒绝右心导管检查,结合病史及其他相关检查结果,除外肺实质疾病、肺血栓栓塞症、结缔组织病及其他药物引起的肺动脉高压,诊断为达沙替尼引起的部分可逆性肺动脉高压,随访至今.共检索到中文文献1篇,英文文献14篇,报道24例患者,其中男12例,女12例,年龄17 ～74岁.结论 达沙替尼可导致部分可逆性肺动脉高压,反复用药后肺动脉高压可能难以逆转.用药期间应监测超声心动图,出现肺动脉高压停药后不建议再次使用达沙替尼.

Objective To study the clinical features and prognosis of pulmonary arterial hypertension related to dasatinib.Methods A case of pulmonary arterial hypertension （PAH） during dasatinib therapy was retrospectively analyzed and the related literature was reviewed.Results A 55-year-old male with chronic myelogenous leukemia was treated with dasatinib at a dosage of 100 mg/d.After 36 months of initiating the therapy,he presented with chest distress,fatigue and general edema.His heart function was graded as NHYA Ⅳ.Transthoracic Doppler echocardiography documented right ventricle enlargement,right ventricular wall thickening,reduction of right ventricular systolic function,widening of the main pulmonary artery and branches,and an estimated systolic pulmonary arterial pressure（SPAP） of 115 mmHg（1 mmHg =0.133 kPa）,with pericardial effusion and normal systolic left ventricular function.Chest ultrasound documented bilateral pleural effusion.The patient had taken and withdrew dasatinib 5 times by himself.The symptom had improved after stopping the drug,with SPAP decreasing to 37-82 mmHg measured by echocardiography at the first 3 times,and the pleural effusion and the pericardial effusion had disappeared.But 1 year after the 4th withdrawal of the drug,his pulmonary arterial pressure had failed to decrease,and he had taken the drug again by himself.Other causes of pulmonary arterial hypertension such as lung parenchymal diseases,pulmonary thromboembolism,connective tissue diseases,other drug induced PAH,were excluded by extensive examinations.The patient refused to receive right-sided heart catheterization.The patient was followed until now.Conclusions Dasatinib can cause partially reversible PAH.But after repeated use of the drug,PAH may become irreversible.Monitoring SPAP by transthoracic Doppler echocardiography is necessary during dasatinib therapy.