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胎儿和新生儿同种免疫性血小板减少症的新进展。

New developments in fetal and neonatal alloimmune thrombocytopenia.

机构信息

Department of Pediatrics, Weill Cornell Medicine, New York, NY.

Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Weill Cornell Medicine, New York, NY.

出版信息

Am J Obstet Gynecol. 2021 Aug;225(2):120-127. doi: 10.1016/j.ajog.2021.04.211. Epub 2021 Apr 8.

Abstract

Fetal and neonatal alloimmune thrombocytopenia, the platelet equivalent of hemolytic disease of the fetus and newborn, can have devastating effects on both the fetus and neonate. Current management of fetal and neonatal alloimmune thrombocytopenia in a subsequent affected pregnancy involves antenatal administration of intravenous immune globulin and prednisone to the pregnant woman to prevent the development of severe fetal thrombocytopenia and secondary intracranial hemorrhage in utero. That therapy has proven to be highly effective but is associated with maternal side effects and is expensive. This commentary describes 4 advances that could substantially change the current approach to detecting and managing fetal and neonatal alloimmune thrombocytopenia in the near future. The first would be an introduction of a program to screen all antepartum patients in this country for pregnancies at risk of developing fetal and neonatal alloimmune thrombocytopenia. Strategies to implement this complex process have been described. A second advance is testing of cell-free fetal DNA obtained from maternal blood to noninvasively determine the fetal human platelet antigen 1 genotype. A third, in preliminary development, is creation of a prophylactic product that would be the platelet equivalent of Rh immune globulin (RhoGAM). Finally, a fourth major potential advance is the development of neonatal Fc receptor inhibitors to replace the current medical therapy administered to pregnant women with an affected fetus. Neonatal Fc receptor recycles plasma immunoglobulin G to increase its half-life and is the means by which immunoglobulin G crosses the placenta from the maternal to the fetal circulation. Blocking the neonatal Fc receptor is an ideal way to prevent maternal immunoglobulin G antibody from causing fetal and neonatal alloimmune thrombocytopenia in a fetus at risk of developing that disorder. The pertinent pathophysiology and rationale for each of these developments will be presented in addition to our thoughts relating to steps that must be taken and difficulties that each approach would face for them to be successfully implemented.

摘要

胎儿和新生儿同种免疫性血小板减少症是胎儿和新生儿溶血病的血小板等同物,可对胎儿和新生儿造成毁灭性影响。目前,在后续受影响的妊娠中,胎儿和新生儿同种免疫性血小板减少症的管理涉及对孕妇进行产前静脉注射免疫球蛋白和泼尼松治疗,以防止胎儿严重血小板减少症和宫内继发性颅内出血的发生。该疗法已被证明非常有效,但与母体副作用有关,且费用昂贵。本文述评介绍了 4 项进展,这些进展可能会在不久的将来极大地改变当前检测和管理胎儿和新生儿同种免疫性血小板减少症的方法。首先是在全国范围内引入一项计划,对所有产前患者进行筛查,以发现有发生胎儿和新生儿同种免疫性血小板减少症风险的妊娠。已描述了实施这一复杂过程的策略。其次是测试从母亲血液中获得的无细胞胎儿 DNA,以无创方式确定胎儿人类血小板抗原 1 基因型。第三,初步开发了一种预防性产品,它将是 Rh 免疫球蛋白(RhoGAM)的血小板等同物。最后,第四个潜在的主要进展是开发新生儿 Fc 受体抑制剂,以替代目前用于治疗受影响胎儿的孕妇的药物治疗。新生儿 Fc 受体可使血浆免疫球蛋白 G 循环,从而延长其半衰期,并且是免疫球蛋白 G 从母体循环向胎儿循环转移的途径。阻断新生儿 Fc 受体是防止母体免疫球蛋白 G 抗体引起胎儿和新生儿同种免疫性血小板减少症的理想方法,而胎儿有发生这种疾病的风险。除了我们对必须采取的步骤和每种方法在成功实施过程中可能面临的困难的想法之外,本文还将介绍这些进展的相关病理生理学和基本原理。

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