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脑胶质瘤术后低纤维蛋白原血症1例临床分析

作者:未知

  【摘要】 纤维蛋白原(FIB)在凝血级联反应、纤维蛋白溶解、应激和炎症中起重要作用。低纤维蛋白原血症目前已知与急性创伤性凝血病、术后出血和不良预后等有关。本研究对1例女性脑胶质瘤术后低纤维蛋白原血症患者进行临床分析, 其磁共振成像显示右侧额颞叶、右侧基底节区占位性病变, 术后病理为胶质瘤。患者术后发生低纤维蛋白原血癥, 其他凝血功能相关指标均正常。经输注血浆以及冷沉淀, 低纤维蛋白原血症得到纠正, 但术后CT发现颅内血肿, 患者最终遗留左侧肢体乏力以及认知障碍而出院, 表明在大量失血、血液稀释、肿瘤本身和手术创伤等综合因素影响容易产生低纤维蛋白原血症, 且与患者术后颅内血肿有关。当围术期血浆FIB浓度低于正常水平时, 应及时纠正。一旦出现严重的血浆FIB缺乏, 应根据实际情况以及自身条件补充FIB。
  【关键词】 低纤维蛋白原血症;脑胶质瘤;纤维蛋白原;颅内血肿;神经外科术后
  DOI:10.14163/j.cnki.11-5547/r.2019.02.070
  【Abstract】 Fibrinogen (FIB) plays an important role in the coagulation cascade, fibrinolysis, stress and inflammation. Low fibrinogenemia is currently known to be associated with acute traumatic coagulopathy, postoperative bleeding, and poor prognosis. In this study, clinical analysis was made on a female patient with hypofibrinogenemia after glioma surgery. Magnetic resonance imaging showed a lesion in the right frontal temporal lobe and right basal ganglia, and the postoperative pathology was glioma. Hypofibrinogenemia occurred after operation, and other coagulation function related indicators were normal. After plasma infusion and cryoprecipitation, hypofibrinogenemia was corrected, but after operation, intracranial hematoma was found on CT, and the patient was discharged from hospital with left limb weakness and cognitive impairment. It is suggested that hypofibrinogenemia is prone to occur due to a combination of factors such as massive blood loss, hemodilution, tumor itself and surgical trauma, and it is related to postoperative intracranial hematoma. When the perioperative plasma FIB concentration is lower than the normal level, it should be corrected in time. In case of severe plasma FIB deficiency, FIB should be supplemented according to the actual situation and its own conditions.
  【Key words】 Hypofibrinogenemia; Glioma; Fibrinogen; Intracranial hematoma; Postoperative neurosurgery
  纤维蛋白原(fibrinogen, FIB)作为一种糖蛋白, 其在肝脏中合成, 并在凝血、血小板聚集、纤维蛋白溶解、炎症和肿瘤生长中发挥重要作用[1]。在凝血过程中, FIB中的血纤肽A和B被凝血酶切割形成纤维蛋白单体, 进而形成纤维蛋白, 稳定血小板的聚集[2]。当血浆中的FIB<1.5 g/L即可诊断为低纤维蛋白原血症[3]。虽然目前对神经外科围术期血浆纤维蛋白原浓度缺乏统一的指南和共识, 但已有研究表明低纤维蛋白原血症与术后颅内血肿的发生相关, 并影响患者的预后[4-6], 因此应引起广大神经外科医生的重视, 围术期应及时纠正低纤维蛋白原血症。本研究中对1例女性脑胶质瘤术后低纤维蛋白原血症患者进行临床分析, 现报告如下。
  1 临床资料
  患者, 女, 41岁, 因反复头痛伴抽搐、视觉模糊1年, 于2017年3月2日入院。入院前的头颅磁共振成像提示右侧额颞叶以及基底节区占位性病变。入院后患者出现急性头痛和呕吐, 不久便昏迷。双侧瞳孔大小不等, 右侧散大;右侧瞳孔直接、间接对光反射消失, 左侧则迟钝。头颅CT显示右侧额颞叶、基底节区占位性病变, 中线结构向左侧移位约1.4 cm。患者术前实验室检查无异常, 也无肝病病史以及异常出血史。遂急诊行开颅肿瘤切除术以及去骨瓣减压术, 手术中肿瘤位于右侧额颞顶、岛叶, 肿瘤组织呈白色冻胶状, 肿瘤边界不清呈侵润性生长, 部分脑组织受压移位, 瘤周水肿明显。在切除过程中可见肿瘤血供丰富, 创面呈弥漫性渗血, 止血较为困难。手术持续约13 h, 最终对肿瘤进行大部分切除。术中出血量约3000 ml, 尿量3250 ml, 输注去白红细胞12 U, 新鲜冷冻血浆1400 ml, 晶体液4500 ml, 胶体液2000 ml。手术结束时, 复查凝血四项提示FIB浓度为1.25 g/L(参考范围2.00~5.00 g/L), 其余凝血指标[凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)、国际标准化比值(INR)、凝血酶原活动度(PTA)、凝血酶时间(TT)、血小板(PLT)]均较术前无异常。患者返回病房后遂输注新鲜冰冻血浆400 ml以及2 U冷沉淀, 其血浆FIB浓度改善并于手术后第3天逐渐恢复正常。而术区范围内的血肿于术后第1天的头颅CT中发现, 经过2周的时间大部分已自行吸收。出院时患者遗留左侧肢体乏力以及认知功能障碍, 其肿瘤标本最终的病理支持星形细胞瘤(Ⅱ~Ⅲ级)的诊断。   2 討论
  Adelmann等[4]发现术后血浆FIB的平均浓度为1.7 g/L的患者, 其发生术后颅内血肿的几率较平均浓度为2.4 g/L的患者更大。而围术期的FIB<1.5 g/L已被证实是术后发生颅内血肿的危险因素[5]。Wei等[6]研究表明在颅内原发性肿瘤患者接受手术治疗后, 血浆FIB浓度的下降与术后颅内出血、预后不良相关。早期的研究发现纤维蛋白可促进肿瘤生长和转移形成, 抑制凝血或促进纤溶[7]。与非肿瘤组织相比, 在原发性恶性脑肿瘤和侵袭性脑转移瘤中尿激酶型纤溶酶原激活物受体(u-PAR)和尿激酶型纤溶酶原激活物(u-PA)的表达增加了30倍, 这意味着在这些肿瘤组织中可能发生纤溶亢进[8]。而脑肿瘤患者发生纤溶亢进也已出现在早期的报道中[9]。近期刘克君等[10]报道了脑肿瘤患者术前即发生低纤维蛋白原血症的病例, 认为脑肿瘤引起的纤溶亢进是可能的原因。开颅手术本身又可进一步加重纤溶亢进[11]。因而纤溶亢进与术后低纤维蛋白原血症的发生有一定关系。研究表明过度的补液以及输血可造成血液稀释[12-14], 引起凝血功能的紊乱。本例患者术中液体入量明显大于出量, 而短期内大量的失血使得血浆中的FIB丢失严重, 难以在短期内恢复。新鲜冰冻血浆中FIB的浓度在1~3 g/L[15]之间。在一项研究中, 按12.2 ml/kg的量对患者输注新鲜冰冻血浆, 血浆FIB仅增加0.4 g/L[16]。这意味着当患者大量失血后, 即使补充了血浆、液体, 患者仍有可能因血液稀释、FIB的严重消耗而发生低纤维蛋白血症。目前国内外对神经外科围术期血浆FIB浓度应维持在怎样的水平以及处理低纤维蛋白原血症仍缺乏统一的共识和指南。2016年发布的修订后的欧洲创伤指南建议, 当血浆FIB<1.5~2.0 g/L[13], 应补充FIB。也是在2016年, 欧洲麻醉学会发布了围手术期发生严重出血的管理指南, 建议对严重出血和血浆FIB<1.5 g/L(或产科出血2.0 g/L)的患者补充FIB[14]。在补充FIB的选择上, 除了血浆之外, 还有FIB浓缩物和冷沉淀。冷沉淀是从血浆中提取的, 富含着高分子的蛋白如FⅧ、von Willebrand因子和FIB, 其中FIB的浓度比血浆中的高很多, 通常为15 g/L[17]。2015年美国麻醉协会发布的围术期血液管理指南建议, 对于围术期严重出血的病人, 当FIB<0.8~1.0g /L时, 应输注冷沉淀[18]。但当患者发生严重出血时, 不推荐单一使用冷沉淀进行止血, 应联合输注血浆以及血小板[19]。FIB浓缩物也是从人血浆中提取的, 是一种经热处理后冻干的粉末[20]。目前, FIB浓缩物在大出血情况下的使用有所增加并取得良好的效果[21, 22]。2018年法国围术期止血工作小组(GIHP)建议使用FIB浓缩物的初始剂量为25~50 mg/kg[23]。总之, 选择FIB浓缩物还是冷冻沉淀作为FIB的补充在各国都存在差异, 也存在着争议[20]。在我国, 对有条件的医院, 仍以冷沉淀作为补充FIB的主要手段。综上所述, 大量失血、血液稀释、肿瘤本身和手术创伤等综合因素影响容易产生低纤维蛋白原血症, 且与患者术后颅内血肿有关。当围术期血浆FIB浓度低于正常水平时, 应及时纠正。一旦出现严重的血浆FIB缺乏, 应根据实际情况以及自身条件补充FIB。
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  [收稿日期:2018-11-12]
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