双胎贫血-红细胞增多序列征分析及文献复习

Twin anemia-polycythemia sequence: a case report and literatures review

目的探讨双胎贫血-红细胞增多序列征(TAPS)的临床特点,并进行文献复习。方法选择2016年5月,四川大学华西第二医院新生儿科收治的单绒毛膜双羊膜囊(MCDA) TAPS新生儿(新生儿1、2)为研究对象。采用回顾性分析方法,收集本对TAPS新生儿的临床病例资料,对其临床特点进行分析。本研究对TAPS文献进行复习时,设定检索策略为:以"双胎贫血红-细胞增多序列征"为关键词,在中国知网、维普中文科技期刊数据库、万方数据知识服务平台中,检索TAPS相关文献,检索时间设定为各数据库建库至2018年8月31日。总结TAPS的临床特点及其诊断、治疗与预后。本研究遵循的程序符合2013年修订的《世界医学协会赫尔辛基宣言》要求。结果①对本对TAPS新生儿母亲的临床资料采集如下:29岁,自然受孕,G_1P_0,孕龄为11^(+6)孕周时,于本院建卡进行定期产前检查,乙型肝炎病毒携带病史20^+年(接受定期随访);孕龄为16^(+5)孕周时,超声检查提示MCDA双活胎。于孕龄为36^(+4)孕周时发现重度妊娠期肝内胆汁淤积症,予以地塞米松促胎肺成熟、保肝及降胆汁酸等治疗1 d后,经剖宫产术分娩一对活男婴。②对本对TAPS新生儿的临床资料采集如下:均为男性,出生胎龄为36^(+5)周。其中,新生儿1:出生体重为2 420 g,生后1、5、10 min Apgar评分均为10分,生后1 h+58 min转入本院新生儿科,全身皮肤红紫,胃管内反复抽出咖啡色胃液,穿刺部位、脐带残端可见渗血。转入本院新生儿科时,血红蛋白(Hb)值为278 g/L,血细胞比容为78.4%,网织红细胞百分比为3.0%,诊断为红细胞增多症等。新生儿2:出生体重为1 870 g,生后1、5、10 min Apgar评分均为10分,生后34 min转入本院新生儿科,全身皮肤苍白、反应差,竖颈差,四肢肌张力减低,原始反射减弱,转入本院新生儿科时,Hb值为63 g/L,血细胞比容为21.2%,网织红细胞百分比为39.7%,诊断为重度新生儿贫血等。新生儿1、2的Hb差值为215 g/L,并且新生儿2与新生儿1网织红细胞百分比的比值为13.2,确诊为TAPS双胎新生儿。新生儿1、2均合并多系统并发症,分别予以部分换血、输血治疗后好转出院,生后随访1年,生长发育均正常。③文献复习结果:按照本研究设定的文献检索策略,共计检索出7篇报道TAPS研究的文献,涉及25对(50例)TAPS新生儿/胎儿的临床特点、诊治及预后等方面研究。其中,受血儿均表现为多血貌,供血儿均表现为贫血貌。50例TAPS新生儿/胎儿的治疗结局为:37例(74.0%)好转出院,1例(2.0%)纳入原始研究时尚未娩出,9例(18.0%)死亡,2例(4.0%)因严重并发症放弃治疗后结局不详,1例(2.0%)新生儿因气腹征转院接受进一步治疗后失访。在37例好转出院的TAPS新生儿中,4例(10.8%)合并低白蛋白血症,4例(10.8%)合并神经系统损害,22例(59.5%)合并心血管系统并发症,14例(37.8%)合并呼吸系统并发症,14例(37.8%)合并新生儿黄疸;对其均缺乏长期随访,长期预后均不详。结论国内报道的TAPS多于生后才被确诊,新生儿临床特点主要为MCDA新生儿的生后Hb差值大(>80 g/L),而羊水量差异不明显,可合并多系统并发症,其长期预后目前尚不明确。对MCDA新生儿的大脑中动脉峰值流速(MCA-PSV)测定与胎盘超声检查,可协助临床于产前尽早诊断TAPS。

Objective To explore the clinical characteristics of twin anemia-polycythemia sequence (TAPS), and review the literatures. Methods On May 2016, a pair of monochorionic-diamniotic (MCDA) TAPS twin newborns (No.1 neonate and No.2 neonate) in Department of Neonatology, West China Second University Hospital, Sichuan University were selected as research subjects. The clinical data of two TAPS neonates were collected by retrospective analysis method, and its clinical features were analyzed. With the keyword of "twin anemia-polycythemia sequence" as Chinese keyword, TAPS-related literatures were searched from China National Knowledge Infrastructure, VIP database, and Wanfang Data Knowledge Service Platform. Literature retrieval time was set from the establishment of database to August 31, 2018. Then relevant literatures were reviewed to summarize the clinical features, diagnosis, treatments and prognosis of TAPS in China. This study was consistent with the requirements of World Medical Association Declaration of Helsinki revised in 2013. Results ①The pregnant mother of the two TAPS neonates was 29 years old, nature conceived, G1P0, who received regular prenatal examinations at 11 +6 gestational weeks in our hospital, and with hepatitis B virus infection for more than 20 years (follow-up regularly). At 16 +5 gestational weeks, ultrasound examination was performed on her and revealed MCDA twins pregnancy. Severe intrahepatic cholestasis of pregnancy was diagnosed at 36 +4 gestational weeks, and then the pregnant mother took dexamethasone to promote fetal lung maturation, hepatoprotective and bile acid lowering therapy. One day later, delivery of a pair of male infants was conducted by cesarean section.②No.1 and No.2 neonates both were male infants at 36 +5 weeks of pregnancy. No.1 neonate with 2 420 g of birth weight, all 10 Apgar scores at 1, 5 and 10 min after birth, was treated in Department of Neonatology in our hospital at 1 h and 58 min after birth. The skin of the whole body was red and purple. Coffee-colored gastric fluid was repeatedly extracted from the stomach tube. Seepage of blood could be found at the site of puncture and the remnant of the umbilical cord. The hemoglobin (Hb) value was 278 g/L, hematocrit was 78.4%, and the percentage of reticulocyte was 3.0% at the time of transferring to Department of Neonatology. He was diagnosed as polycythemia and so on. No. 2 neonate with 1 870 g of birth weight, all 10 Apgar scores at 1, 5 and 10 min after birth, was transferred to the Department Neonatology of our hospital at 34 min after birth. The whole body was pale, the reaction was poor, the vertical neck was poor, the muscle tension of the limbs was reduced, and the original reflex was weakened. The Hb value was 63 g/L, hematocrit was 21.2%, and the percentage of reticulocyte was 39.7% at the time of transferring to Department of Neonatology. He was diagnosed as severe neonatal anemia and so on. No.1 neonate of the TAPS twins was characterized with sanguineous appearance, while No.2 neonate suffered from anemia. The difference of Hb level between twins was 215 g/L, and the ratio of reticulocyte percentage was 13.2, so they were finally diagnosed as TAPS twins. Various complications that involved multiple systems were documented in both of the twins. Partial exchange transfusion and blood transfusion were administrated according to the clinical manifestations separately. The follow-up for one year after discharge suggested normal growth and development for both of the twins.③Literatures review revealed 7 Chinese reports about TAPS according to the literature search strategy in this study, including 25 twins (50 cases) of TAPS neonates/ fetuses, and their clinical characteristics, diagnosis and treatment, and prognosis. All of the donor babies showed anemia appearance, while their twins were sanguineous appearance. Among the 50 cases of TAPS neonates/ fetuses, 37 cases (74.0%) discharged from hospital, and 9 of them (18.0%) died, while 2 babies (4.0%) were with unexpected outcome after giving up treatment due to serious complications. One of them (2.0%) was lost from the follow-up after transferring to other hospital for further treatment due to neonatal pneumoperitoneum. While the remaining one (2.0%) was still a fetus when included in original study. Among the 37 cases of TAPS neonates discharged from hospital, hypoalbuminemia was documented in 4 of them (10.8%), while neurological complications in 4 babies (10.8%), cardiac complications in 22 babies (59.5%) and respiratory complications in 14 babies (37.8%). Neonatal jaundice was observed in 14 babies (37.8%). There were no data about long-term follow-up, and the long-term prognoses of them all were unknown. Conclusions TAPS in China was mainly diagnosed when the babies were born. The obvious differences of Hb level between the MCDA twins (>80 g/L), while without obvious differences of amniotic fluid volume is the main clinical feature of TAPS, and multiple system complications can be observed. The long-term prognosis of TAPS is still unknown with insufficient data available. Middle cerebral artery peak flow velocity (MCA-PSV) measurements of MCDA neonates and placental ultrasonography can be helpful for the early prenatal diagnosis of TAPS.