抗癫痫药物治疗后发生低纤维蛋白原血症的临床研究  

Hypofibrinogenemia after treatment with antiseizure medications

作　　者：董燕[1] 史亚丽 苏彤 贾天明[1] 徐瑞娟 梅道启[3] 崔甲昱 杜开先[1] 金亮 张晓莉[1] DONG Yan;SHI Ya-li;SU Tong;JIA Tian-ming;XU Rui-juan;MEI Dao-qi;CUI Jia-yu;DU Kai-xian;JIN Liang;ZHANG Xiao-li(Department of Pediatric Neurology,the Third Affiliated Hospital of Zhengzhou University,Zhengzhou,Henan 450052,China;Department of Medication Administration,the Third Affiliated Hospital of Zhengzhou University,Zhengzhou,Henan 450052,China;Department of Neurology,Zhengzhou Children's Hospital,Zhengzhou,Henan 450018,China)

机构地区：[1]郑州大学第三附属医院小儿神经内科,河南郑州450052 [2]郑州大学第三附属医院医务部,河南郑州450052 [3]郑州市儿童医院神经内科,河南郑州450018

出　　处：《中华实用诊断与治疗杂志》2023年第5期480-485,共6页Journal of Chinese Practical Diagnosis and Therapy

基　　金：河南省小儿脑损伤重点实验室暨河南省儿科疾病临床医学研究中心联合开放课题(KFKT2021003);河南省儿童神经发育工程研究中心开放课题(SG201910);河南省医学科技攻关计划联合共建项目(LHGJ20190339)。

摘　　要：目的 观察癫痫患儿规范应用抗癫痫发作药物(antiseizure medications, ASMs)或联合糖皮质激素治疗后低纤维蛋白原血症发生情况及严重程度,探讨抗癫痫治疗后发生低纤维蛋白原血症的因素和治疗结局。方法 33例应用ASMs或联合糖皮质激素规范治疗后发生低纤维蛋白原血症的癫痫患儿,确诊低纤维蛋白原血症后给予人纤维蛋白原、必要时降低丙戊酸钠药物剂量等治疗。记录癫痫发作类型、综合征类型、病因、治疗后发生低纤维蛋白原血症的中位时间、发生低纤维蛋白原血症时的治疗方案;于抗癫痫治疗前、诊断低纤维蛋白原血症时、低纤维蛋白原血症治疗次日及治疗后1个月检测纤维蛋白原(fibrinogen,Fib)、凝血酶原时间、凝血酶时间、活化部分凝血活酶时间、纤维蛋白降解产物、D-二聚体、中性粒细胞计数、白细胞计数、血红蛋白、血小板计数。随访至2022年8月,观察患儿低纤维蛋白原血症复发情况。结果 33例发作类型为痉挛发作24例,强直-阵挛发作6例,强直痉挛发作2例,肌阵挛发作1例;婴儿癫痫性痉挛综合征21例;病因不明14例,结构性病因13例,遗传性病因6例;1例因不易止血发现且合并轻度肝功能损伤,余32例在随访期间常规检测血常规、凝血功能时发现。诊断低纤维蛋白原血症时,33例中32例应用丙戊酸钠,其中26例(含21例婴儿癫痫性痉挛综合征)应用糖皮质激素联合丙戊酸钠等ASMs, 1例应用糖皮质激素联合左乙拉西坦、托吡酯及氯硝西泮,6例未应用糖皮质激素(5例应用丙戊酸钠联合其他ASMs, 1例单用丙戊酸钠)。诊断低纤维蛋白原血症时Fib水平[0.930(0.850, 0.980)g/L]低于抗癫痫治疗前[2.460(2.140, 2.675)g/L](Z=-5.013,P<0.001),凝血酶时间[(20.676±1.756)s]长于抗癫痫治疗前[(18.284±1.605)s](t=7.478,P<0.001),活化部分凝血活酶时间[(34.803±5.446)s]短于抗癫痫治疗前[(40.447±5.402)s](t=-6.030,P<0.00Objective To observe the occurrence and severity of hypofibrinogenemia in children with epilepsy after glucocorticoid(GC)treatment or combined with standardized antiseizure medications(ASMs),and to explore the influencing factors and treatment outcomes of hypofibrinogenemia.Methods Thirty-three children with epilepsy developed hypofibrinogenemia after standardized ASMs or combined with GC treatment,and were given human fibrinogen supplementation after confirming the diagnosis of hypofibrinogenemia,and if necessary,the sodium valproate dose was reduced.The types of seizures,syndrome and etiologies,median time of hypofibrinogenemia after treatment,and treatment options at the diagnosis of hypofibrinogenemia were observed.The levels of fibrinogen,prothrombin time,thrombin time,activated partial thromboplastin time,fiber degradation products,D-dimer,absolute neutrophil count,white blood cell count,hemoglobin and platelet count were recorded before antiseizure treatment,at the diagnosis of hypofibrinogenemia,the next day after treatment and one month after treatment of hypofibrinogenemia.The follow up was conducted till August 2022to observe the recurrence of hypofibrinogenemia.Results In 33patients,the seizures were classified as spastic seizures in 24patients,tonic-clonic in 6,tonic spasm in 2,and myoclonic in 1.Twenty-one patients were diagnosed as infantile epileptic spasms syndrome.The etiology was unclear in 14patients,structural in 13,and genetic in 6.Hypofibrinogenemia was detected due to difficulty in stopping bleeding and mild liver dysfunction in 1patient,and during blood routine and coagulation function test during follow-up in 32 patients.At the time of hypofibrinogenemia diagnosis,32of 33patients received sodium valproate,of which 26patients(including 21patients with infantile spasms syndrome)received GC combined with sodium valproate and other ASMs,1patient received GC combined with levetiracetam,topiramate and clonazepam,and 6patients received no GC(including 5received sodium valproate combined with ot

关 键 词：癫痫 儿童 低纤维蛋白原血症 丙戊酸钠 糖皮质激素 

分 类 号：R742.1[医药卫生—神经病学与精神病学] R725.5[医药卫生—临床医学]