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2025 | OriginalPaper | Buchkapitel

26. Fetale Thrombozytopenie

verfasst von : Prof. Dr. med. Ulrich Gembruch

Erschienen in: Ultraschalldiagnostik in Geburtshilfe und Gynäkologie

Verlag: Springer Berlin Heidelberg

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Zusammenfassung

Bereits in der 7.–8. SSW p.m. sind fetale Thrombozyten nachweisbar, deren mittlere Konzentration im Lauf der Schwangerschaft von etwa 160/nl im I. Trimester auf 250/nl im II. und III. Trimester ansteigt. Thrombozytopenien des Fetus können verschiedene Ursachen haben. Bereits pränatal und dies sogar in der Indexschwangerschaft kann insbesondere die fetale und neonatale Alloimmunthrombozytopenie (FNAIT) zu bedeutsamen Hirnblutungen des Fetus und Neugeborenen führen. Die frühzeitig einsetzende, wöchentlich zu wiederholende, intravenöse Gabe von hochdosierten Immunglobulin G kann die Zerstörung der fetalen Thrombozyten eindämmen und eine pränatale Hirnblutung effektiv verhindern.

Vorheriges Kapitel Hydrops fetalis und fetale Anämie

Nächstes Kapitel Chromosomale und nicht chromosomale Fehlbildungssyndrome

Alm J, Duong Y, Wienzek-Lischka S, Cooper N, Santoso S, Sachs UJ, Kiefel V, Bein G (2022) Anti-human platelet antigen-5b antibodies and fetal and neonatal alloimmune thrombocytopenia; incidental association or cause and effect? Br J Haematol 198:14–23PubMedCrossRef

Altarescu G, Elda-Geva T, Grisaru-Granovsky S, Bonstein L, Miskin H, Varshver I, Margalioth EJ, Levy-Lahad E, Renbaum P (2012) Preimplantation genetic diagnosis for fetal neonatal alloimmune thrombocytopenia due to antihuman platelet antigen maternal antibodies. Obstet Gynecol 119:338–343PubMedCrossRef

Arinsburg SA, Shaz BH, Westhoff C, Cushing MM (2012) Determination of human platelet antigen typing by molecular methods: Importance in diagnosis and early treatment of neonatal alloimmune thrombocytopenia. Am J Hematol 87:525–528PubMedCrossRef

Berkowitz RL, Kolb EA, McFarland JG, Wissert M, Primani A, Lesser M, Bussel JB (2006) Parallel randomized trials of risk–based therapy for fetal alloimmune thrombocytopenia. Obstet Gynecol 107:91–96PubMedCrossRef

Bertrand G, Drame M, Martageix C, Kaplan C (2011) Prediction of the fetal status in noninvasive management of alloimmune thrombocytopenia. Blood 117:3209–3213PubMedCrossRef

Bertrand G, Petermann R, Kaplan C (2014) Prediction of IVIG treatment efficiency in fetal/neonatal alloimmune thrombocytopenia. Blood 124:654–655PubMedCrossRef

Boulot P, Cattaneo A, Taib J, Peray P, Lefort G, Hedon B, Laffargue F, Viala JL (1993) Hematologic values of fetal blood obtained by means of cordocentesis. Fetal Diagn Ther 8:309–316PubMedCrossRef

Bussel JB, Berkowitz RL, Lynch L, Lesser ML, Paidas MJ, Huang CL, McFarland JG (1996) Antenatal management of alloimmune thrombocytopenia with intravenous gamma-globulin: a randomized trial of the addition of low-dose steroid to intravenous gamma-globulin. Am J Obstet Gynecol 174:1414–1423PubMedCrossRef

Bussel JB, Zabusky MR, Berkowitz RL, McFarland JG (1997) Fetal alloimmune thrombocytopenia. N Engl J Med 337:22–26PubMedCrossRef

Bussel JB, Sola-Visner M (2009) Current approaches to the evaluation and management of the fetus and neonate with immune thrombocytopenia. Semin Perinatol 33:35–42PubMedCrossRef

Bussel JB, Berkowitz RL, Hung C, Kolb EA, Wissert M, Primiani A, Tsaur FW, Macfarland JG (2010) Intracranial hemorrhage in alloimmune thrombocytopenia: stratified management to prevent recurrence in the subsequent affected fetus. Am J Obstet Gynecol 203:135.e1–135.e14PubMedCrossRef

Bussel JB, Vander Haar EL, Berkowitz RL (2021) New developments in fetal and neonatal alloimmune thrombocytopenia. Am J Obstet Gynecol 225:120–127PubMedCrossRef

Bussel JB, Hou M, Cines DB (2023) Management of primary immune thrombocytopenia in pregnancy. N Engl J Med;389:540–548PubMedCrossRef

Bussel JB, Knightly KA (2024) Immune thrombocytopenia (ITP) in pregnancy. Br J Haematol 204:1176–1177PubMedCrossRef

Castleman JS, Moise KJ Jr, Kilby MD (2021) Medical therapy to attenuate fetal anaemia in severe maternal red cell alloimmunisation. Br J Haematol 192:425–432PubMedCrossRef

Ciobanu AM, Dumitru AE, Gica N, Botezatu R, Peltecu G, Panaitescu AM (2020) Benefits and risks of IgG transplacental transfer. Diagnostics 10:583PubMedPubMedCentralCrossRef

Ernstsen SL, Ahlen MT, Johansen T, Bertelsen EL, Kjeldsen-Kragh J, Tiller H (2022) Antenatal intravenous immunoglobulins in pregnancies at risk of fetal and neonatal alloimmune thrombocytopenia: comparison of neonatal outcome in treated and nontreated pregnancies. Am J Obstet Gynecol 227:506.e1–e12PubMedCrossRef

Farley A, Lloyd S, Dayton M, Biben C, Stonehouse O, Taoudi S (2021) Severe thrombocytopenia is sufficient for fetal and neonatal intracerebral hemorrhage to occur. Blood 138:885–897PubMedCrossRef

Farley AM, Dayton M, Biben C, Stonehouse O, Terreaux A, Taoudi S (2022) Cerebral vasculature exhibits dose-dependent sensitivity to thrombocytopenia that is limited to fetal/neonatal life. Blood 139:2355–2360PubMedCrossRef

Geisen C, Kjaer M, Fleck E, Skogen B, Armstrong R, Behrens F, Bhagwagar Z, Braeuninger S, Mortberg A, Olsen KJ, Gastón Schäfer SM, Walter C, Seifried E, Wikman A, Kjeldsen-Kragh J, Koehm M (2023) An HPA-1a-positive platelet-depleting agent for prevention of fetal and neonatal alloimmune thrombocytopenia: a randomized, single-blind, placebo-controlled, single-center, phase 1/2 proof-of-concept study. J Thromb Haemost 21:838–849

Jauniaux E, Pahal G, Gervy C, Gulbis B (2000) Blood biochemistry and endocrinology in the human fetus between 11 and 17 weeks of gestation. Reprod Biomed Online 1:38–44PubMedCrossRef

Kamphuis MM, Paridaans N, Porcelijn L, De Haas M, Van Der Schoot CE, Brand A, Bonsel GJ, Oepkes D (2010) Screening in pregnancy for fetal or neonatal alloimmune thrombocytopenia: systematic review. BJOG 117:1335–1343PubMedCrossRef

Kamphuis MM, Oepkes D (2011) Fetal and neonatal alloimmune thrombocytopenia: prenatal interventions. Prenat Diagn 31:712–719PubMedCrossRef

Kamphuis MM, Paridaans NP, Porcelijn L, Lopriore E, Oepkes D (2014) Incidence and consequences of neonatal alloimmune thrombocytopenia: a systematic review. Pediatrics 133:715–721PubMedCrossRef

Kjaer M, Bertrand G, Bakchoul T, Massey E, Baker JM, Lieberman L, Tanael S, Greinacher A, Murphy MF, Arnold DM, Baidya S, Bussel J, Hume H, Kaplan C, Oepkes D, Ryan G, Savoia H, Shehata N, Kjeldsen-Kragh J, International Collaboration for Transfusion Medicine Guidelines (2018) Maternal HPA-1a antibody level and its role in predicting the severity of Fetal/Neonatal Alloimmune Thrombocytopenia: a systematic review. Vox Sang 114:79–94PubMedCrossRef

Kjær M, Geisen C, Akkök ÇA, Wikman A, Sachs U, Bussel JB, Nielsen K, Walles K, Curtis BR, Vidarsson G, Järås K, Skogen B (2020) Strategies to develop a prophylaxis for the prevention of HPA-1a immunization and fetal and neonatal alloimmune thrombocytopenia. Transfus Apher Sci 59:102712PubMedCrossRef

Kjeldsen-Kragh J, Bengtsson J (2020) Fetal and neonatal alloimmune thrombocytopenia – new prospects for fetal risk assessment of HPA-1a-negative pregnant women. Transfus Med Rev 34:270–276PubMedCrossRef

Kjeldsen-Kragh J, Hellberg Å (2022) Noninvasive prenatal testing in immunohematology – clinical, echnical and ethical considerations. J Clin Med 11:2877PubMedPubMedCentralCrossRef

Kjeldsen-Kragh J, Skogen B (2013) Mechanisms and prevention of alloimmunization in pregnancy. Obstet Gynecol Surv 68:526–532PubMedCrossRef

Kjeldsen-Kragh J, Ni H, Skogen B (2012) Towards a prophylactic treatment of HPA-related foetal and neonatal alloimmune thrombocytopenia. Curr Opin Hematol 19:469–474PubMedCrossRef

Kjeldsen-Kragh J, Fergusson DA, Kjaer M, Lieberman L, Greinacher A, Murphy MF, Bussel J, Bakchoul T, Corke S, Bertrand G, Oepkes D, Baker JM, Hume H, Massey E, Kaplan C, Arnold DM, Baidya S, Ryan G, Savoia HF, Landry D, Shehata N (2020) Fetal/neonatal alloimmune thrombocytopenia: a systematic review of impact of HLA-DRB3*01:01 on fetal/neonatal outcome. Blood Adv 4:3368–3377PubMedPubMedCentralCrossRef

Kjeldsen-Kragh J, Bein G, Tiller H (2023) Pregnant women at low risk of having a child with fetal and neonatal alloimmune thrombocytopenia do not require treatment with intravenous immunoglobulin. J Clin Med 12:5492PubMedPubMedCentralCrossRef

Knightly KA, Bussel JB, McKelvy M, Vander Haar E (2024) Does absence of intracranial hemorrhage in the first pregnancy in fetal and neonatal alloimmune thrombocytopenia preclude occurrence in the second? Am J Hematol 99:468–472PubMedCrossRef

Koyama S, Tomimatsu T, Kanagawa T, Kumasawa K, Tsutsui T, Kimura T (2012) Reliable predictors of neonatal immune thrombocytopenia in pregnant women with idiopathic thrombocytopenic purpura. Am J Hematol 87:15–21PubMedCrossRef

Lieberman L, Greinacher A, Murphy MF, Bussel J, Bakchoul T, Corke S, Kjaer M, Kjeldsen-Kragh J, Bertrand G, Oepkes D, Baker JM, Hume H, Massey E, Kaplan C, Arnold DM, Baidya S, Ryan G, Savoia H, Landry D, Shehata N, International Collaboration for Transfusion Medicine Guidelines (ICTMG) (2019) Fetal and neonatal alloimmune thrombocytopenia: recommendations for evidence-based practice, an international approach. Br J Haematol 185:549–562PubMedCrossRef

Martí-Carvajal AJ, Peña-Martí GE, Comunián-Carrasco G (2009) Medical treatments for idiopathic thrombocytopenic purpura during pregnancy. Cochrane Database Syst Rev 4:CD7722

Moise KJ Jr, Oepkes D, Lopriore E, Bredius RGM (2022) Targeting neonatal Fc receptor: potential clinical applications in pregnancy. Ultrasound Obstet Gynecol 60:167–175PubMedCrossRef

Moise KJ, Jr., Ling LE, Oepkes D, Tiblad E, Verweij E, Lopriore E, Smoleniec J, Sachs UJ, Bein G, Kilby MD, Miller RS, Devlieger R, Audibert F, Emery SP, Markham K, Norton ME, Ocón-Hernández O, Pandya P, Pereira L, Silver RM, Windrim R, Streisand JB, Leu JH, Mirza A, Smith V, Schwartz LB, Tjoa ML, Saeed-Khawaja S, Komatsu Y, Bussel JB (2024) Nipocalimab in early-onset severe hemolytic disease of the fetus and newborn. N Engl J Med. 391:526–537

Mørtberg TV, Zhi H, Vidarsson G, Foss S, Lissenberg-Thunnissen S, Wuhrer M, Michaelsen TE, Skogen B, Stuge TB, Andersen JT, Newman PJ, Ahlen MT (2022) Prevention of fetal/neonatal alloimmune thrombocytopenia in mice: biochemical and cell biological characterization of isoforms of a human monoclonal antibody. Immunohorizons 6:90–103PubMedCrossRef

Nedberg NH, Turowski G, Guz K, Przytuła E, Uhrynowska M, Roald B, Husebekk A, Sitras V, Nystad M, Dębska M, Brojer E, Tiller H (2021) Platelet alloimmunization is associated with low grade chronic histiocytic intervillositis – a new link to a rare placental lesion? Placenta 112:89–96PubMedCrossRef

Ouzegdouh Mammasse Y, Chenet C, Drubay D, Martageix C, Cartron JP, Vainchenker W, Petermann R (2020) A new efficient tool for non-invasive diagnosis of fetomaternal platelet antigen incompatibility. Br J Haematol 190:787–798PubMedCrossRef

Pacheco LD, Berkowitz RL, Moise KJ Jr, Bussel JB, McFarland JG, Saade GR (2011) Fetal and neonatal alloimmune thrombocytopenia: a management algorithm based on risk stratification. Obstet Gynecol 118:1157–1163PubMedCrossRef

Paridaans NP, Kamphuis MM, Taune Wikman A, Tiblad E, van den Akker ES, Lopriore E, Challis D, Westgren M, Oepkes D (2015) Low-dose versus standard-dose intravenous immunglobulin to prevent fetal intracranial hemorrhage in fetal and neonatal alloimmune thrombocytopenia: a randomized trial. Fetal Diagn Ther 38:147–153PubMedCrossRef

Patel DD, Bussel JB (2020) Neonatal Fc receptor in human immunity: Function and role in therapeutic intervention. J Allergy Clin Immunol 146:467–478PubMedCrossRef

Poon MC, d’Oiron R (2018) Alloimmunization in congenital deficiencies of platelet surface glycoproteins: focus on Glanzmann’s thrombasthenia and bernard-Soulier’s syndrome. Semin Thromb Hemost 44:604–614PubMedCrossRef

Porcelijn L, Van den Akker ES, Oepkes D (2008) Fetal thrombocytopenia. Semin Fetal Neonatal Med 13:223–230PubMedCrossRef

Rayment R, Brunskill SJ, Soothill PW, Roberts DJ, Bussel JB, Murphy MF (2011) Antenatal interventions for fetomaternal alloimmune thrombocytopenia. Cochrane Database Syst Rev 5:CD4226

Regan F, Lees CC, Jones B, Nicolaides KH, Wimalasundera RC, Mijovic A, Royal College of Obstetricians and Gynaecologists (2019) Prenatal management of pregnancies at risk of fetal neonatal alloimmune thrombocytopenia (FNAIT): Scientific Impact Paper No. 61. BJOG 126:e173–e185PubMedCrossRef

Santoso S, Wihadmadyatami H, Bakchoul T, Werth S, Al-Fakhri N, Bein G, Kiefel V, Zhu J, Newman PJ, Bayat B, Sachs UJ (2016) Antiendothelial αvβ3 antibodies are a major cause of intracranial bleeding in fetal/neonatal alloimmune thrombocytopenia. Arterioscler Thromb Vasc Biol 36:1517–1524PubMedPubMedCentralCrossRef

Serrarens-Janssen VM, Semmekrot BA, Novotny VM, Porcelijn L, Lotgering FK, Delemarre FM, Steegers EA (2008) Fetal/neonatal allo-immune thrombocytopenia (FNAIT): past, present, and future. Obstet Gynecol Surv 63:239–252PubMedCrossRef

Tiller H, Kamphuis MM, Flodmark O, Papadogiannakis N, David AL, Sainio S, Koskinen S, Javela K, Wikman AT, Kekomaki R, Kanhai HH, Oepkes D, Husebekk A, Westgren M (2013) Fetal intracranial haemorrhages caused by fetal and neonatal alloimmune thrombocytopenia: an observational cohort study of 43 cases from an international multicentre registry. BMJ Open 3:e2490PubMedPubMedCentralCrossRef

Tiller H, Husebekk A, Skogen B, Kjeldsen-Kragh J, Kjaer M (2016) True risk of fetal/neonatal alloimmune thrombocytopenia in subsequent pregnancies: a prospective observational follow-up study. BJOG 123:738–744PubMedCrossRef

Tiller H, Ahlen MT, Akkök ÇA, Husebekk A (2020) Fetal and neonatal alloimmune thrombocytopenia – the Norwegian management model. Transfus Apher Sci 59:102711PubMedCrossRef

Tiller H, Tiblad E, Baker P, van Valkenburgh H, Fennema H, Nelson R, Lam E, Meizlik P (2024) Design of a phase 3, multicenter, randomized, placebo-controlled, double-blind study of nipocalimab in pregnancies at risk for fetal and neonatal alloimmune thrombocytopenia (FREESIA-1). Oral presentation at the Fetal Medicine Foundation World Congress, June 25–29

Vandenbussche FPHA, Brand A, Kanhai HHH (2011) Fetal thrombocytopenia. In: James D, Steer PJ, Weiner CP, Gonik B, Crowther CA, Robson SC (Hrsg) High risk pregnancy: management options, 4. Aufl. Saunders, St. Louis, S 229–237CrossRef

Visweshwar N, Ayala I, Jaglal M, Killeen R, Sokol L, Laber DA, Manoharan A (2022) Primary immune thrombocytopenia: a ‘diagnosis of exclusion’? Blood Coagul Fibrinolysis 33:289–294PubMedPubMedCentral

de Vos TW, Winkelhorst D, de Haas M, Lopriore E, Oepkes D (2020) Epidemiology and management of fetal and neonatal alloimmune thrombocytopenia. Transfus Apher Sci 59:102704PubMedCrossRef

de Vos TW, Winkelhorst D, Baelde HJ, Dijkstra KL, van Bergen RDM, van der Meeren LE, Nikkels PGJ, Porcelijn L, van der Schoot CE, Vidarsson G, Eikmans M, Kapur R, van der Keur C, Trouw LA, Oepkes D, Lopriore E, van der Hoorn MP, Bos M, de Haas M (2021) Placental complement activation in fetal and neonatal alloimmune thrombocytopenia: an observational study. Int J Mol Sci 22:6763PubMedPubMedCentralCrossRef

de Vos TW, de Haas M, Oepkes D, Tan RNGB, van der Schoot CE, Steggerda SJ, de Vries LS, Lopriore E, van Klink JMM (2022a) Long-term neurodevelopmental outcome in children after antenatal intravenous immune globulin treatment in fetal and neonatal alloimmune thrombocytopenia. Am J Obstet Gynecol 227:637.e1–637.e9PubMedCrossRef

de Vos TW, Winkelhorst D, Árnadóttir V, van der Bom JG, Canals Surís C, Caram-Deelder C, Deschmann E, Haysom HE, Hverven HBC, Lozar Krivec J, McQuilten ZK, Muñiz-Diaz E, Nogués N, Oepkes D, Porcelijn L, van der Schoot CE, Saxonhouse M, Sola-Visner M, Tiblad E, Tiller H, Wood EM, Young V, Železnik M, de Haas M, Lopriore E (2022b) Postnatal treatment for children with fetal and neonatal alloimmune thrombocytopenia: a multicentre, retrospective, cohort study. Lancet Haematol 9:e844–e853PubMedCrossRef

de Vos TW, Winkelhorst D, Porcelijn L, Beaufort M, Oldert G, van der Bom JG, Lopriore E, Oepkes D, de Haas M, van der Schoot E (2023) Natural history of human platelet antigen 1a-alloimmunised pregnancies: a prospective observational cohort study. Lancet Haematol 10:e985–e993PubMedCrossRef

Winkelhorst D, Murphy MF, Greinacher A, Shehata N, Bakchoul T, Massey E, Baker J, Lieberman L, Tanael S, Hume H, Arnold DM, Baidya S, Bertrand G, Bussel J, Kjaer M, Kaplan C, Kjeldsen-Kragh J, Oepkes D, Ryan G (2017) Antenatal management in fetal and neonatal alloimmune thrombocytopenia: a systematic review. Blood 129:1538–1547PubMedCrossRef

Winkelhorst D, Kamphuis MM, Steggerda SJ (2019) Perinatal outcome and long-term neurodevelopment after intracranial haemorrhage due to fetal and neonatal alloimmune thrombocytopenia. Fetal Diagn Ther 45:184–191PubMedCrossRef

Yougbaré I, Lang S, Yang H, Chen P, Zhao X, Tai WS, Zdravic D, Vadasz B, Li C, Piran S, Marshall A, Zhu G, Tiller H, Killie MK, Boyd S, Leong-Poi H, Wen XY, Skogen B, Adamson SL, Freedman J, Ni H (2015) Maternal anti-platelet β3 integrins impair angiogenesis and cause intracranial hemorrhage. J Clin Invest 125:1545–1556PubMedPubMedCentralCrossRef

Yougbaré I, Tai WS, Zdravic D et al (2017) Activated NK cells cause placental dysfunction and miscarriages in fetal alloimmune thrombocytopenia. Nat Commun 8:224PubMedPubMedCentralCrossRef

Titel: Fetale Thrombozytopenie
verfasst von: Prof. Dr. med. Ulrich Gembruch
Verlag: Springer Berlin Heidelberg
Buch: Ultraschalldiagnostik in Geburtshilfe und Gynäkologie
Print ISBN: 978-3-662-67372-0

Electronic ISBN: 978-3-662-67373-7

Copyright-Jahr: 2025
DOI: https://doi.org/10.1007/978-3-662-67373-7_26

Springerpflege

Zusammenfassung

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