The elucidation of amniotic fluid embolism

羊水栓塞的阐明

• 批准号: 12671589
• 负责人: OI Hidekazu
• 金额: $ 2.3万
• 依托单位: HAMAMATSU UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12671589/
• 关键词: amniotic fluid embolism; Sialyl Tn; Zinc coproporphyrinl; Sialyl Tn; Zinc coproporphyrinl; Sialyl・Tn; Zinc coproporphrin 1; 亜鉛コプロポルフィリン I; アナフィラキシーショック

We classified AFE patients into two groups. One is the established AFE group : fetal materials are found in maternal pulmonary vessels at autopsy. Another is the potential AFE group who fills with modified Benson's criteria. 1) currently pregnant or within 12 hours after delivery, 2) one or more of the following to require medical treatment severely, a) cardiac arrest b) large amount of bleeding after delivery within 2 hours (more than 1500ml except for atonic bleeding), c) disseminated intravascular coagulation, d) respiratory distress, 3) absence of other medical explanations for clinical course. We discovered specific fetal antigens, Sialyl Tn (STN) and Zinc coproporphyrin1 (Zn-CP1), which present in meconium and developed quantitative methods to determine fetal antigen leakage into maternal circulation. One hundred thirty five patients, 20 with established AFE and in 115 with potential AFE, were recruited from institutions all over the world including Japan. These patients were ava … More ilable to evaluate the STN and Zn-CP1 level in serum. The cut-off points in serum were provided 46.0U/ml(STN) and 1.6pmol/ml (Zn-CP1), respectively, as mean plus 2SD. The serum levels of STN and Zn-CP1 in 135 patients with AFE showed higher concentrations than those in control(STN:163.4±229.1U/ml [established AFE], 70.5±198.5 [potential AFE]vs. 29.5±8.8U/ml [control], Zn-CP1:30.2±26.7pmol/ml[established AFE], 84.0±193.9 [potential AFE] vs. 0.50±0.54pmol/ml[control]). Positive rate of STN in patients with AFE, established AFE and potential AFE was 84.6% and 18.5% respectively. Meanwhile positivity of Zn-CP1 was 75.0% and 57.0%, respectively. The findings of AFE in lung sections were divided 2 types. One was that the structure of the lung tissues were almost normal when the patients died within 1 day. This cause of death was the dysfunction of pulmonary ventilated system and circulation, because the embolus and fibrin deposite could be found out intra pulmonary vessels. Second was that the structure of the lung tissues were almost destroyed similar to adult respiratoly distress syndrome when the patients died after a few days. The leukocytes in the region of pulmonaty vasculature, where the TKH-2 immunostaining was positive, were mainly composed of neutrophils. Using a monoclonal antibody against neutrophil elastase, this region showed strong staining for neutrophils. It is conceivable that the activated neutrophils-derived hypercytokinemia may result in the cause of death of AFE after a few days. In concern of this result, the inflammatory cytokine IL-8 was measured in the patients with AFE. IL-8 in the died patients was significant higher than in the survived patients. We suggest when the values of IL-8 are indicated over 400pg/ml, the prognosis of AFE patients is poor. An updated analysis, preterm labor and pre-eclampsia was approved more in the patients with AFE compared with the other complication. The appearance of AFE was occurred frequently in both multipara and inducted delivery. The pregnant women with multipara and the complications of preterm labor and pre-eclampsia should not be inducted easily without the medical indication. The registration system of AFE was started from August 2003 officially in the society of Japan obstetrics and gynecology. The registration of the patients with AFE are rapidly increasing. Less

我们将AFE患者分为两组。一个是已建立的AFE组：在尸检时，在母亲的肺血管中发现了胎儿物质。另一种是潜在的AFE组，他们用修改后的Benson标准填充。1)正在怀孕或分娩后12小时内；2)下列一种或多种严重需要治疗的疾病；a)心脏骤停；b)产后2小时内大量出血(除紧张性出血外，超过1500毫升)；c)弥漫性血管内凝血；d)呼吸窘迫；3)临床病程缺乏其他医学解释。我们发现了胎粪中存在的特异性胎儿抗原唾液酸氨基转移酶(STN)和锌协同卟啉1(Zn-CP1)，并建立了检测胎儿抗原渗入母体循环的定量方法。从包括日本在内的世界各地的机构招募了135名患者，其中20名已确诊为AFE，115名可能患有AFE。这些患者都是AVA…更不能评估血清中STN和锌-CP1的水平。血清分界点分别为46.0U/m l(STN)和1.6pm o l/m l(锌-CP1)，平均值+2SD。血清STN和锌-CP1水平明显高于对照组(STN：163.4±229.1U/ml，70.5±198.5[潜在AFE]比29.5±8.8U/ml，锌-CP1：30.2±26.7pmol/ml[建立AFE]，84.0±193.9[潜在AFE]比0.50±0.54pmol/ml]。STN在AFE、既往AFE和潜在AFE患者中的阳性率分别为84.6%和18.5%。同时，锌-CP1的阳性率分别为75.0%和57.0%。肺切片的AFE表现可分为两种类型。一种是患者在1天内死亡时肺组织结构基本正常。死亡原因为肺内血管内可见栓子和纤维蛋白沉积，导致肺呼吸系统和循环功能障碍。第二，患者几天后死亡，肺组织结构几乎被破坏，类似于成人呼吸窘迫综合征。TKH-2免疫染色阳性的肺血管区域的白细胞主要由中性粒细胞组成。使用抗中性粒细胞弹性蛋白酶的单抗，该区域中性粒细胞染色较深。可以想象，激活的中性粒细胞衍生的高细胞分裂素血症可能导致几天后AFE的死亡。为此，对AFE患者的炎性细胞因子IL-8进行了检测。死亡组IL-8水平显著高于存活组。提示当IL-8>400pg/ml时，AFE患者预后较差。最新的分析显示，与其他并发症相比，早产和先兆子痫在AFE患者中得到了更多的认可。AFE的出现在经产妇和引产中均较常见。对经产妇及有早产、先兆子痫并发症的孕妇，在无内科指征的情况下，不宜轻易引产。日本妇产科学会从2003年8月起正式启动AFE注册制度。AFE患者的登记人数正在迅速增加。较少

项目成果

大井豪一: "【産婦人科救急治療ガイド】産科救急疾患とその初期治療 母体 羊水塞栓症"産婦人科治療. 84. 784-786 (2002)

大井刚一：《【妇产科急救指南】产科急救疾病及其初期治疗孕产妇羊水栓塞》妇产科治疗. 84. 784-786（2002）。

H.Kobayashi: "Histological diagnosis of amniotic fluid embolism by monoclonal antibody TKH-2 that recognizes NeuAc α2-6GalNAc epitope."Hum Pathol. 28. 428-433 (1997)

H.Kobayashi：“通过识别 NeuAc α2-6GalNAc 表位的单克隆抗体 TKH-2 进行羊水栓塞的组织学诊断。”Hum Pathol。28. 428-433 (1997)

大井豪一: "【妊娠中の肺の生理と肺疾患】羊水塞栓"産婦人科の世界. 53. 45-49 (2001)

Goichi Oi：“[怀孕期间的肺生理学和肺部疾病]羊水栓塞”《妇产科世界》53. 45-49 (2001)。

大井豪一: "周産期の出血と血栓症"金原出版(In press). (2004)

大井刚一：“围产期出血和血栓形成”金原出版社（2004 年出版）。

Michael D.Benson, Hiroshi Kobayashi, Richar K.Silver, Hidekazu Oi, Paul A.Greenberger, Toshihiko Terao: "Immunologic studies in presumed amniotic fluid embolism."Obstet Gynecol. 97. 510-514 (2001)

Michael D.Benson、Hiroshi Kobayashi、Richar K.Silver、Hidekazu Oi、Paul A.Greenberger、Toshihiko Terao：“假定羊水栓塞的免疫学研究。”Obstet Gynecol。