Fetale und neonatale Alloimmunthrombozytopenie, Teil 2

Zusammenfassung

Die fetale und neonatale Alloimmunthrombozytopenie (FNAIT) wird durch mütterliche Antikörper hervorgerufen, die gegen ein vom Vater ererbtes Blutgruppenmerkmal an fetalen Thrombozyten gerichtet sind. Während Teil 1 des Beitrags Ausgabe die Ätiologie, die Pathogenese und die Diagnostik der FNAIT thematisiert hatte, widmet sich dieser 2. Teil der Risikostratifizierung und Behandlung [1].

Abstract

Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a bleeding condition caused by maternal antibodies against fetal platelet antigens inherited from the father. The incidence of severe FNAIT (neonatal platelet count < 50 G/l) is 1 in 2500 live births. Its most severe consequence, intracranial hemorrhage, leading to death or neurologic disability, occurs in 10 per 100 000 neonates, commonly prior to birth. This review summarizes the current knowledge on the management of pregnancies at risk, and prophylaxis in this part no. 2, while the 1st part presented the incidence, pathogenesis as well as the diagnosis of FNAIT.

Schlüsselwörter

fetale und neonatale Alloimmunthrombozytopenie - FNAIT - neonatale Thrombozytopenie - nichtinvasive Pränataldiagnostik

Key words

fetal and neonatal alloimmune thrombocytopenia - FNAIT - neonatal thrombocytopenia - non-invasive prenatal diagnosis

• Literatur

• 1 Sachs UJ, Bedei I, Wienzek-Lischka S. et al. Fetale und neonatale Alloimmunthrombozytopenie, Teil 1: Ätiologie, Pathogenese und Diagnostik. Transfusionsmedizin 2021; 11: 112-126
• 2 Tiller H, Husebekk A, Skogen B. et al. True risk of fetal/neonatal alloimmune thrombocytopenia in subsequent pregnancies: a prospective observational follow-up study. BJOG 2016; 123: 738-744
• 3 Radder CM, Brand A, Kanhai HHH. Will it ever be possible to balance the risk of intracranial haemorrhage in fetal or neonatal alloimmune thrombocytopenia against the risk of treatment strategies to prevent it?. Vox Sang 2003; 84: 318-325
• 4 Bussel JB, Berkowitz RL, Hung C. et al. Intracranial hemorrhage in alloimmune thrombocytopenia: stratified management to prevent recurrence in the subsequent affected fetus. Am J Obstet Gynecol 2010; 203: 135
• 5 Sachs UJ. Prospects for risk stratification of anti-HPA-1a alloimmunized pregnant women. Transfus Apher Sci 2020; 59: 102709
• 6 Kapur R, Kustiawan I, Vestrheim A. et al. A prominent lack of IgG1-Fc fucosylation of platelet alloantibodies in pregnancy. Blood 2014; 123: 471-480
• 7 Sonneveld ME, Natunen S, Sainio S. et al. Glycosylation pattern of anti-platelet IgG is stable during pregnancy and predicts clinical outcome in alloimmune thrombocytopenia. Br J Haematol 2016; 174: 310-320
• 8 Santoso S, Wihadmadyatami H, Bakchoul T. et al. Antiendothelial αvβ3 antibodies are a major cause of intracranial bleeding in fetal/neonatal alloimmune thrombocytopenia. Arterioscler Thromb Vasc Biol 2016; 36: 1517-1524
• 9 Kjaer M, Bertrand G, Bakchoul T. et al. Maternal HPA-1a antibody level and its role in predicting the severity of Fetal/Neonatal Alloimmune Thrombocytopenia: a systematic review. Vox Sang 2019; 114: 79-94
• 10 Lo YM, Hjelm NM, Fidler C. et al. Prenatal diagnosis of fetal RhD status by molecular analysis of maternal plasma. N Engl J Med 1998; 339: 1734-1738
• 11 Scheffer PG, Ait Soussan A, Verhagen O. et al. Noninvasive fetal genotyping of human platelet antigen-1a. BJOG 2011; 118: 1392-1395
• 12 Ferro M, Macher HC, Fornés G. et al. Noninvasive prenatal diagnosis by cell-free DNA screening for fetomaternal HPA-1a platelet incompatibility. Transfusion 2018; 58: 2272-2279
• 13 Nogués N. Recent advances in non-invasive fetal HPA-1a typing. Transfus Apher Sci 2020; 59: 102708
• 14 Wienzek-Lischka S, Krautwurst A, Fröhner V. et al. Noninvasive fetal genotyping of human platelet antigen-1a using targeted massively parallel sequencing. Transfusion 2015; 55: 1538-1544
• 15 Orzińska A, Guz K, Mikula M. et al. Prediction of fetal blood group and platelet antigens from maternal plasma using next-generation sequencing. Transfusion 2019; 59: 1102-1107
• 16 Wienzek-Lischka S, Bachmann S, Froehner V. et al. Potential of next-generation sequencing in noninvasive fetal molecular blood group genotyping. Transfus Med Hemother 2020; 47: 14-22
• 17 Moise KJ, Carpenter RJ. Increased severity of fetal hemolytic disease with known rhesus alloimmunization after first-trimester transcervical chorionic villus biopsy. Fetal Diagn Ther 1990; 5: 76-78
• 18 Axt-Fliedner R, Wienzek-Lischka S, Sachs UJ. et al. Hämolytische Erkrankung des Fetus und Neugeborenen. Transfusionsmedizin 2018; 8: 95-110
• 19 Regan F, Lees CC, Jones B. et al. Prenatal management of pregnancies at risk of fetal neonatal alloimmune thrombocytopenia (FNAIT): Scientific impact paper no. 61. BJOG 2019; 126: e173-e185
• 20 Refsum E, Håkansson S, Mörtberg A. et al. Intracranial hemorrhages in neonates born from 32 weeks of gestation-low frequency of associated fetal and neonatal alloimmune thrombocytopenia: a register-based study. Transfusion 2018; 58: 223-231
• 21 Girard N, Chaumoitre K, Confort-Gouny S. et al. Magnetic resonance imaging and the detection of fetal brain anomalies, injury, and physiologic adaptations. Curr Opin Obstet Gynecol 2006; 18: 164-176
• 22 Daffos F, Forestier F, Muller JY. et al. Prenatal treatment of alloimmune thrombocytopenia. Lancet 1984; 2: 632
• 23 Paidas MJ, Berkowitz RL, Lynch L. et al. Alloimmune thrombocytopenia: Fetal and neonatal losses related to cordocentesis. Am J Obstet Gynecol 1995; 172: 475-479
• 24 Overton TG, Duncan KR, Jolly M. et al. Serial aggressive platelet transfusion for fetal alloimmune thrombocytopenia: platelet dynamics and perinatal outcome. Am J Obstet Gynecol 2002; 186: 826-831
• 25 Bussel JB, Berkowitz RL, McFarland JG. et al. Antenatal treatment of neonatal alloimmune thrombocytopenia. N Engl J Med 1988; 319: 1374-1378
• 26 Winkelhorst D, Murphy MF, Greinacher A. et al. Antenatal management in fetal and neonatal alloimmune thrombocytopenia: a systematic review: A systematic review. Blood 2017; 129: 1538-1547
• 27 Lieberman L, Greinacher A, Murphy MF. et al. Fetal and neonatal alloimmune thrombocytopenia: recommendations for evidence-based practice, an international approach. Br J Haematol 2019; 185: 549-562
• 28 Bundesärztekammer. Querschnitts-Leitlinien zur Therapie mit Blutkomponenten und Plasmaderivaten. Gesamtnovelle 2020. Im Internet (Stand: 17.05.2021): https://www.bundesaerztekammer.de/fileadmin/user_upload/downloads/pdf-Ordner/MuE/Querschnitts-Leitlinien__BAEK__zur_Therapie_mit_Blutkomponenten_und_Plasmaderivaten_-_Gesamtnovelle_2020.pdf
• 29 Wienzek-Lischka S, Sawazki A, Ehrhardt H. et al. Non-invasive risk-assessment and bleeding prophylaxis with IVIG in pregnant women with a history of fetal and neonatal alloimmune thrombocytopenia: management to minimize adverse events. Arch Gynecol Obstet 2020; 302: 355-363
• 30 Rossi KQ, Lehman KJ, OʼShaughnessy RW. Effects of antepartum therapy for fetal alloimmune thrombocytopenia on maternal lifestyle. J Matern Fetal Neonatal Med 2016; 29: 1783-1788
• 31 Herrmann A, Samelson-Jones BJ, Brake S. et al. IVIG-associated maternal pancytopenia during treatment for neonatal alloimmune thrombocytopenia. AJP Rep 2017; 7: e197-e200
• 32 Radder CM, Haan MJJ de Brand A. et al. Follow up of children after antenatal treatment for alloimmune thrombocytopenia. Early Hum Dev 2004; 80: 65-76
• 33 van den Akker ES, Oepkes D, Brand A. et al. Vaginal delivery for fetuses at risk of alloimmune thrombocytopenia?. BJOG 2006; 113: 781-783
• 34 de Vos TW, Winkelhorst D, de Haas M. et al. Epidemiology and management of fetal and neonatal alloimmune thrombocytopenia. Transfus Apher Sci 2020; 59: 102704
• 35 Tiller H, Ahlen MT, Akkök ÇA. et al. Fetal and neonatal alloimmune thrombocytopenia – The Norwegian management model. Transfus Apher Sci 2020; 59: 102711
• 36 Kjeldsen-Kragh J, Ahlen MT. Foetal and neonatal alloimmune thrombocytopenia – The role of the HLA-DRB3*01:01 allele for HPA-1a-immunisation and foetal/neonatal outcome. Transfus Apher Sci 2020; 59: 102707
• 37 Dame C. Neonatale Thrombozytopenie. Monatsschr Kinderheilkd 2018; 166: 959-967
• 38 Kamphuis MM, Paridaans NP, Porcelijn L. et al. Incidence and consequences of neonatal alloimmune thrombocytopenia: a systematic review. Pediatrics 2014; 133: 715-721
• 39 Morrone K. Thrombocytopenia in the newborn. Neoreviews 2018; 19: e34-e41
• 40 Holzhauer S, Zieger B. Diagnosis and management of neonatal thrombocytopenia. Semin Fetal Neonatal Med 2011; 16: 305-310
• 41 Sola-Visner M, Saxonhouse MA, Brown RE. Neonatal thrombocytopenia: what we do and donʼt know. Early Hum Dev 2008; 84: 499-506
• 42 Winkelhorst D, Kamphuis MM. et al. Kloet LC de et al. Severe bleeding complications other than intracranial hemorrhage in neonatal alloimmune thrombocytopenia: a case series and review of the literature. Transfusion 2016; 56: 1230-1235
• 43 Kovanlikaya A, Tiwari P, Bussel JB. Imaging and management of fetuses and neonates with alloimmune thrombocytopenia. Pediatr Blood Cancer 2017; 64
• 44 Sparger KA, Assmann SF, Granger S. et al. Platelet transfusion practices among very-low-birth-weight infants. JAMA Pediatr 2016; 170: 687-694
• 45 Curley A, Stanworth SJ, Willoughby K. et al. randomized trial of platelet-transfusion thresholds in neonates. N Engl J Med 2019; 380: 242-251
• 46 Fustolo-Gunnink SF, Fijnvandraat K, van Klaveren D. et al. Preterm neonates benefit from low prophylactic platelet transfusion threshold despite varying risk of bleeding or death. Blood 2019; 134: 2354-2360
• 47 Baker JM, Shehata N, Bussel J. et al. Postnatal intervention for the treatment of FNAIT: a systematic review. J Perinatol 2019; 39: 1329-1339
• 48 Allen DL, Samol J, Benjamin S. et al. Survey of the use and clinical effectiveness of HPA-1a/5b-negative platelet concentrates in proven or suspected platelet alloimmunization. Transfus Med 2004; 14: 409-417
• 49 Roberts I, Stanworth S, Murray NA. Thrombocytopenia in the neonate. Blood Rev 2008; 22: 173-186
• 50 Chakravorty S, Roberts I. How I manage neonatal thrombocytopenia. Br J Haematol 2012; 156: 155-162
• 51 Kjeldsen-Kragh J, Killie MK, Tomter G. et al. A screening and intervention program aimed to reduce mortality and serious morbidity associated with severe neonatal alloimmune thrombocytopenia. Blood 2007; 110: 833-839
• 52 Kjær M, Geisen C, Akkök ÇA. et al. Strategies to develop a prophylaxis for the prevention of HPA-1a immunization and fetal and neonatal alloimmune thrombocytopenia. Transfus Apher Sci 2020; 59: 102712