培门冬酰胺酶引起的颅内静脉窦血栓形成8例临床分析  

Cerebral venous sinus thrombosis caused by pegasparaginase: a clinical analysis of 8 cases

作　　者：颜银燕 刘宏涌[2] 余莉华[1] 林丹娜[1] 黄露露 赖肖蓉 张亚芥 资娟 吴莉 廖旭 杨丽华[1] Yan Yinyan;Liu Hongyong;Yu Lihua;Lin Danna;Huang Lulu;Lai Xiaorong;Zhang Yajie;Zi Juan;Wu Li;Liao Xu;Yang Lihua(Department of Pediatric Hematology,Zhujiang Hospital,Southern Medical University,Guangzhou 510282,China;Department of Pediatrics,Foshan Women and Children Hospital,Foshan 528000,China)

机构地区：[1]南方医科大学珠江医院小儿血液科,广州510282 [2]广东省佛山市妇幼保健院儿科,佛山518000

出　　处：《中华神经医学杂志》2022年第5期462-468,共7页Chinese Journal of Neuromedicine

摘　　要：目的探讨培门冬酰胺酶(PEG-Asp)引起的颅内静脉窦血栓形成(CVST)的危险因素和预后。方法南方医科大学珠江医院小儿血液科自2016年12月至2021年7月采用PEG-Asp化疗252例急性淋巴细胞白血病(ALL)患儿,其中合并CVST 8例。回顾性分析PEG-Asp引起的CVST患儿的临床表现、实验室检查和影像学特征、治疗及预后。结果(1)4例CVST发生在诱导缓解阶段,3例发生在再诱导阶段,1例发生在巩固阶段。2例患儿接受PEG-Asp化疗1次后发生CVST,1例接受PEG-Asp化疗2次后发生CVST,5例接受PEG-Asp化疗2次以上后发生CVST。发生CVST的时间距末次使用PEG-Asp的中位时间为20.5 d。(2)临床表现为阵发性头痛(4例)、恶心或呕吐(3例)、抽搐(2例)、持续性视物模糊(1例)。(3)CVST的发生部位依次为乙状窦(6例)、横窦(4例)、上矢状窦(4例),其中1例合并左侧额顶叶及右侧顶叶皮层出血,1例合并可逆性后部白质脑病综合征,8例患儿均未合并其他部位血栓。(4)部分患儿凝血功能异常,发生CVST时3例患儿纤维蛋白原下降,2例抗凝血酶Ⅲ下降,3例D-二聚体升高。(5)6例患儿使用低分子肝素(LMWH)治疗,其中4例序贯使用利伐沙班,1例序贯使用华法林。抗凝总疗程为56 d。(6)6例患儿经治疗后症状均消失,4例复查磁共振静脉造影(MRV)显示血栓消失,2例血栓范围缩小。1例合并颅内出血的患儿未再使用PEG-Asp,7例在后续化疗期间再次使用PEG-Asp,其中1例再次合并CVST,经抗凝治疗后血栓范围缩小。结论ALL患儿在应用PEG-Asp化疗期间出现无法解释的神经系统症状时,需高度警惕CVST发生,应尽早行头颅增强MRI和MRV以早期诊断。部分患儿合并凝血功能异常,LMWH、华法林和利伐沙班抗凝治疗有效,预后良好,无后遗症。大部分患儿再次使用PEG-Asp不会再次发生CVST。Objective To investigate the risk factors and prognoses of cerebral venous sinus thrombosis(CVST)caused by pegasparaginase(PEG-Asp).Methods A total of 252 children with acute lymphoblastic leukemia(ALL)were treated with PEG-Asp chemotherapy in our hospital from December 2016 to July 2021,including 8 children with CVST.The clinical manifestations,laboratory and imaging features,treatments and prognoses of these children with CVST caused by PEG-Asp were analyzed retrospectively.Results(1)CVST occurred during induction chemotherapy in 4 children,during re-induction chemotherapy in 3 children,and during consolidation stage in one child.CVST occurred in two children who received PEG-ASP chemotherapy once,in one child who received PEG-Asp chemotherapy twice,and 5 children who received PEG-Asp chemotherapy more than twice.The median time between CVST occurrence and last treatment of PEG-Asp was 20.5 d.(2)The clinical manifestations included paroxysmal headache(n=4),nausea or vomiting(n=3),convulsions(n=2)and persistent blurred vision(n=1).(3)CVST appeared at the sigmoid sinus(n=6),transverse sinus(n=4)and superior sagittal sinus(n=4),of which one child was complicated with hemorrhage in left frontal parietal and right parietal cortex,and one with reversible posterior encephalopathy syndrome;8 children were not complicated with thrombus in other parts.(4)Some of the children were complicated with abnormal blood coagulation.When CVST occurred,fibrinogen level decreased in 3 children,anti-thrombin III level decreased in 2 children,and D-dimer level increased in 3 children.(5)Six children were treated with low molecular weight heparin(LMWH),of which,4 were treated with rivasaban and one with warfarin sequentially.The total course of anticoagulation was 56 d.(6)The symptoms of 6 children disappeared after anticoagulation;Magnetic resonance venography(MRV)showed disappeared thrombus in 4 children and reduced thrombus range in 2 children.One child with intracranial hemorrhage did not use PEG-Asp anymore;7 accepted PEG-Asp furt

关 键 词：急性淋巴细胞白血病 培门冬酰胺酶 颅内静脉窦血栓形成 儿童 

分 类 号：R743.3[医药卫生—神经病学与精神病学]