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2019, Número 3

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Rev Cubana Pediatr 2019; 91 (3)


Conocimientos actuales sobre la patogénesis, presentación clínica, diagnóstico y manejo de la trombocitopenia neonatal aloinmune

Soler NG, Romero DY, Forrellat BM, Bencomo HA

Idioma: Español
Referencias bibliográficas: 62
Paginas: 1-18
Archivo PDF: 572.40 Kb.


RESUMEN

Introducción: La trombocitopenia neonatal aloinmune es una enfermedad producida por anticuerpos maternos contra antígenos plaquetarios fetales heredados del padre. Puede ser causa de hemorragia intracraneal y conducir a la muerte o discapacidad en el feto/neonato. Aunque es la causa más grave de trombocitopenia en el neonato y la más común en los recién nacidos a término, en general ha sido poco investigada.
Objetivos: Exponer los conocimientos actuales sobre la patogénesis, presentación clínica, diagnóstico y del manejo pre- y posnatal de la trombocitopenia neonatal aloinmune,
Métodos: Se realizó una revisión de la literatura, en inglés y español, a través del sitio web PubMed y el motor de búsqueda Google académico de artículos publicados en los últimos 10 años. Se hizo un análisis y resumen de la bibliografía revisada.
Resultados: Los anticuerpos IgG maternos son transportados a través de la placenta a la circulación fetal, opsonizan las plaquetas fetales que son removidas por fagocitosis. Los antígenos más implicados son el HPA-1a y HPA-4a. La fisiopatología de la enfermedad es muy similar a la enfermedad hemolítica perinatal, pero aún no se han implementado programas de pesquisa y el diagnóstico se realiza después del nacimiento del niño afectado de trombocitopenia, hemorragia intracraneal o muerte in útero de causa no explicada.
Consideraciones finales: El impacto clínico de la trombocitopenia neonatal aloinmune y las oportunidades de tratamiento potencian la necesidad de implantar programas de pesquisa para la detección de fetos en riesgo de padecer esta enfermedad.


REFERENCIAS (EN ESTE ARTÍCULO)

  1. Brojer E, Husebekk A, Debska M, Uhrynowska M, Guz K, Orzinska A. et al. Fetal/Neonatal Alloimmune Thrombocytopenia: Pathogenesis, Diagnostics and Prevention. Arch Immunol Ther. Exp. 2016:64:279-90. doi: 10.1007/s00005-015-0371-9.

  2. Metcalfe P, Watkins NA, Ouwehand WH. Nomenclature of Human Platelet Antigens. Vox Sang. 2003;85:240-5. doi: 10.1046/j.1423-0410.2003.00331.x.

  3. Peterson J, Pechauer S, Gitter M, Kanack A, Curtis B, Reese J, et al. New platelet glycoprotein polymorphisms causing maternal immunization and neonatal alloimmune thrombocytopenia. Transfusion. 2012;52:1117-24. doi: 10.1111/j.1537-2995.2011.03428.x.

  4. Curtis BR, McFarland JG. Human platelet antigens-2013. Vox Sang. 2014;106:93-102. doi: 10.1111/vox.12085.

  5. Zdravic D, Yougbare I, Vadasz B, Li C, Marshall AH, Chen P, et al. Fetal and neonatal alloimmune thrombocytopenia. Sem Fetal Neonatal Med. 2016;21:19-27. doi: 10.1016/j.siny.2015.12.004.

  6. Curtis BR. Recent progress in understanding the pathogenesis of fetal and neonatal alloimmune thrombocytopenia. Br JHaematol. 2015;171:671-82. doi: 10.1111/bjh.13639.

  7. Kamphuis MM, Paridaans NP, Porcelijn L, Lopriore E, Oepkes D. Incidence and consequences of neonatal alloimmune thrombocytopenia: a systematic review. Pediatrics. 2014; 133:715-21. doi: 10.1542/PEDS.2013-3320

  8. Vadasz Brian PC, Yougbare I, Zdravic D, Li J, Li C, Carrim N, et al. Platelets and platelet alloantigens: lessons from human patients and animal models of fetal and neonatal alloimmune thrombocytopenia. Genes Dis. 2015;2(2):173-85. doi: 10.1016/j.gendis. 2015.02.003

  9. Dubruc E, Lebreton F, Giannoli C, Rabilloud M, Huissoud C, Devouassoux-Shisheboran M, et al. Placental histological lesions in fetal and neonatal alloimmune thrombocytopenia: A retrospective cohort study of 21 cases. Placenta. 2016;48:104-9. doi: 10.1016/j.placenta. 2016.10.009.

  10. Ronzoni S, Keunen J, Shah PS, Kelly EN, Windrim R, Seaward PG, et al. Management and Neonatal Outcomes of Pregnancies with Fetal/Neonatal Alloimmune Thrombocytopenia: A Single-Center Retrospective Cohort Study. Fetal DiagnTher. 2019;45:85-93. doi: 10.1159/000487303.

  11. Hurtado B, Trakala M, Ximénez-EmbúnP, El BakkaliA, Partida D, Sanz-CastilloB, et al. Thrombocytopenia-associated mutations in Ser/Thr kinase MASTL deregulate actin cytoskeletal dynamics in platelets. J Clin Invest. 2018;128(12):5351-67. doi: org/10.1172/JCI121876.

  12. Ya F, TianJ, Li Q, ChenL, RenJ, ZhaoY, et al. Cyanidin-3-O-β-glucoside, a Natural Polyphenol, Exerts Proapoptotic Effects on Activated Platelets and Enhances Megakaryocytic Proplatelet Formation. J Agric Food Chem. 2018;66(41):10712-20. doi: 10.1021/acs.jafc.8b03266

  13. Cloutier N, Allaeys I, Marcoux G, Machlus KR, Mailhot B, Zufferey A, et al. Platelets release pathogenic serotonin and return to circulation after immune complex-mediated sequestration. PNAS. 2018;115(7): E1550-E1559. doi: 10.1073/pnas.1720553115.

  14. Aster RH, Newman PJ. HPA-1a/b (PLA1/A2, Zwa/b): The Odyssey of an alloantigen system. Immunohematology. 2007;23:1-8.

  15. Wu GG. Detection of clinically relevant platelet antibodies in the Asian population. ISBT Sc Ser. 2014;9:112-7. doi:10.1111/VOXS.12098.

  16. Norton A, Allen DL, Murphy MF. Review. Platelet alloantigens and antibodies and clinical significance. Immunohematology. 2004;20 (2):89-99.

  17. Winkelhorst D, Kamphuis MM, de Kloet LC, Zwaginga JJ, Oepkes D, Lopriore E. Severe bleeding complications other than intracranial hemorrhage in neonatal alloimmune thrombocytopenia: a case series and review of the literature. Transfusion. 2016;56:1230-35. doi: 10.1111/trf.13550.

  18. Delbos F, Bertrand G, Croisille L, Ansart-Pirenne H, Bierling P, Kaplan C. Fetal and neonatal alloimmune thrombocytopenia: predictive factors of intracranial hemorrhage. Transfusion. 2016; 56(1):59-66. doi: 10.1111/trf.13274.

  19. Santoso S, Wihadmadyatami H, Bakchoul T, Werth S, Al-Fakhri N, Bein G, et al. Antiendothelial alphavbeta3 antibodies are a major cause of intracranial bleeding in fetal/neonatal alloimmune thrombocytopenia. ArteriosclerThromb Vasc Biol. 2016;36:1517-24. doi: 10.1161/ATVBAHA.116.307281.

  20. Yougbaré I, Lang S, Yang H, Chen P, Zhao X, Tai WS, et al. Maternal anti-platelet β3 integrins impair angiogenesis and cause intracranial hemorrhage. J Clin Invest. 2015; 125(4):1545-56. doi: 10.1172/JCI77820.

  21. Murphy MF, Hambley H, Nicolaides K, Waters AM. Severe fetomaternalalloimmune thrombocytopenia presenting with fetal hydrocephalus. Prenat Diagn. 1996;16:1152-5. doi:10.1002/(SICI)1097-0223(199612)16:12<1152:AID-PD8>3.0.CO;2-J.

  22. Stanworth SJ, Hockett GA, Williamsom LM. Fetomaternal alloimmune thrombocytopenia presenting antenatal as hydrops fetalis. Prenat Diagn. 2001;21:423-4. doi: 10.1002/pd.84.

  23. Muñiz E, Ginovart G. Trombocitopenia aloinmune en el feto y en el recién nacido. An Pediatr. 2003;58:562-7. doi: 10.1016/S1695-4033(03)78122-3.

  24. Campbell-Lee SA, de Santis Parsons D, Sue Shirey R, Kickler TS. Neonatal alloimmune thrombocytopenia due to anti-HPA-5b (Bra). Immunohematology. 2003;19(4):127-31.

  25. Kaplan C. Neonatal alloimmune thrombocytopenia: a 50 year story. Immuno-hematology. 2007;23:9-13.

  26. Tiller H, Husebekk A, Ahlen MT, Stuge TB, Skogen B. Current perspectives on fetal and neonatal alloimmune thrombocytopenia– increasing clinical concerns and new treatment opportunities. Internat J Women’s Health. 2017;9:223-34. doi: 10.2147/IJWH.S90753

  27. Soler Noda G, Aquino Rojas S, Bencomo Hernández A, Sosa González L. Trombocitopenias neonatales en La Habana: incidencia y características de la enfermedad. Rev Cubana Hematol Inmunol Hemoter. 2017;33(3). Acceso: 08/11/2017. Disponible en: http://www.revhematologia.sld.cu/index.php/hih/article/view/518

  28. Bessos H, Turner M, Urbaniak SJ. Is there a relationship between anti-HPA-1a concentration and severity of neonatal alloimmune thrombocytopenia? Immunohematology. 2005;21:102-8.

  29. Petermann R. Thirty years of platelet immunology in fetal and neonatal alloimmune thrombocytopenia management, current situation. Transfus Clin Biol. 2017;24(3):166-71. doi: 10.1016/j.tracli.2017.05.010.

  30. Winkelhorst D, Murphy MF, Greinacher A, Shehata N, Bakchoul T, Massey E, et al. Antenatal management in fetal and neonatal alloimmune thrombocytopenia: a systematic review. Blood. 2017;129(11):1538-47. doi: 10.1182/blood-2016-10-739656.

  31. Williamson LM, Hackell G, Rennie J. Williamson LM., Hackett G, Rennie J, et al. The natural history of fetomaternalalloimmunization to the platelet specific antigen HPA-1a (PLA1, Zwa) as determined by antenatal screening. Blood.1998;92: 2280-7

  32. Wienzek-Lischka S, König IR, Papenkort EM, Hackstein H, Santoso S, Sachs UJ, et al. HLA-DRB3*01:01 is a predictor of immunization against human platelet antigen-1a but not of the severity of fetal and neonatal alloimmune thrombocytopenia. Transfusion. 2017;57(3):533-40. doi: 10.1111/trf.13950.

  33. Carmo JCD, Klippel PS, Cordeiro SDC, Fernandes ÂMDS, Pinto RM, Weber SS, et al. Molecular typing of human platelet antigens in immune thrombocytopenia patients in northern Brazil. Rev Bras Hematol Hemoter. 2017;39(2):122-6. doi: 10.1016/j.bjhh.2017.01.003.

  34. Di Cristofaro J, Frassati C, Montagnie R, Basire A, Merieux Y, Picard C. Identification of anti-HPA-1a allo-antibodies using IgG platelet antibody detection and crossmatch system assay with Galileo Echo. Platelets. 2015;26(5):421-4. doi: 10.3109/09537104.2014.945409.

  35. Wienzek-Lischka S, König IR, Papenkort EM, Hackstein H, Santoso S, Sachs UJ, et al. HLA-DRB3*01:01 is a predictor of immunization against human platelet antigen-1a but not of the severity of fetal and neonatal alloimmune thrombocytopenia. Transfusion. 2017;57(3):533-40. doi: 10.1111/trf.13950.

  36. Sainio S, Javela K, Tuimala J. and Haimila, K. Maternal HLA genotyping is not useful for predicting severity of fetal and neonatal alloimmune thrombocytopenia. Br J Haematol, 2017; 176:111-7. doi:10.1111/bjh.14385.

  37. Semana G, Zazoun T, Alizadeh M, Morel-Kopp MC, Genetet B, Kaplan C. Genetic susceptibility and anti-human platelet antigen 5b alloimmunization. Role of HLA class II and TAP genes. Hum Immunol. 1996;46:114-9. doi: 10.1016/0198-8859(96)00019-5.

  38. Reiher VSA, Hönger G, Infanti L, Passweg JR, Hösli I, Frey BM, et al. Human platelet antigen antibody induction in uncomplicated pregnancy is associated with HLA sensitization. Transfusion. 2017;57(5):1272-9. doi: 10.1111/trf.14053.

  39. Ronzoni S, Keunen J, Shah PS, Kelly EN, Windrim R, Seaward PG, et al. Management and Neonatal Outcomes of Pregnancies with Fetal/Neonatal Alloimmune Thrombocytopenia: A Single-Center Retrospective Cohort Study. Fetal Diagn Ther. 2019;45(2):85-93. doi: 10.1159/000487303.

  40. Aebisher D1, Bartusik D2, Tabarkiewicz J. Laser flow cytometry as a tool for the advancement of clinical medicine. Biomed Pharmacother. 2017;85:434-43. doi: 10.1016/j.biopha.2016.11.048.

  41. Orzińska A, Guz K, Uhrynowska M, Dębska M, Mikula M, Ostrowski J, et al. Noninvasive prenatal HPA-1 typing in HPA-1a negative pregnancies selected in the Polish PREVFNAIT screening program. Transfusion. 2018;58(11):2705-11. doi: 10.1111/trf.14963.

  42. Jain NC, Dhawedkar RG, Vegad JL, Kono CS. Detection of antiplatelet antibody: comparison of platelet immunofluorescence, agglutination, and immunoinjury tests using rabbit antiequine platelet serum. Vet Clin Pathol. 1991;20(1):23-29.

  43. Sarkar RS, Philip J, Jain N. Detection and Identification of Platelet-Associated Alloantibodies by a Solid-Phase Modified Antigen Capture Elisa (MACE) Technique and Its Correlation to Platelet Refractoriness in Multi platelet Concentrate Transfused Patients. Indian J Hematol Blood Transfus. 2015;31(1):77-84. doi: 10.1007/s12288-014-0374-4.

  44. Sarkar RS, Philip J, and Jain N. Detection and Identification of Platelet-Associated Alloantibodies by a Solid-Phase Modified Antigen Capture Elisa (MACE) Technique and Its Correlation to Platelet Refractoriness in Multi platelet Concentrate Transfused Patients. Indian J Hematol Blood Transfus. 2015;31(1):77-84. doi: 10.1007/s12288-014-0374-4.

  45. Zhou S, Liang X, Wang N, Shao L, Yu W, Liu M. Association of human platelet antigen polymorphisms with platelet count and mean platelet volume. Hematology. 2018;23(8):517-21. doi: 10.1080/10245332.2018.1445580.

  46. Cooper N, Bein G, Heidinger K, Santoso S, Sachs UJ. A bead-based assay in the work-up of suspected platelet alloimmunization. Transfusion. 2016;56(1):115-8. doi: 10.1111/trf.13351.

  47. Metzner K, Bauer J, Ponzi H, Ujcich A, Curtis BR. Detection and identification of platelet antibodies using a sensitive multiplex assay system-platelet antibody bead array. Transfusion. 2017;57(7):1724-1733. doi: 10.1111/trf.14122.

  48. Hayashi T, Hirayama F. Advances in alloimmune thrombocytopenia: perspectives on current concepts of human platelet antigens, antibody detection strategies, and genotyping. Blood Transfus. 2015;13: 380-90. doi: 10.2450/2015.0275-14.

  49. Wienzek-Lischka S, Krautwurst A, Frohner V, Hackstein H, Gattenlöhner S, Bräuninger A, et al. Noninvasive fetal genotyping of human platelet antigen-1a using targeted massively parallel sequencing. Transfusion. 2015;55(6):1538-44. doi:10.1111/trf.13102.

  50. Li RS, Ling B, Lu P. Development of quantitative monoclonal antibody-specific immobilization of platelet antigens assay for antibodies against human platelet antigen-1a, 3a, and 5b. Platelets. 2018;29(1):71-5. doi: 10.1080/09537104.2017.1294681.

  51. Lucas G, Poles A, Woźniak MJ, Gilmore R. Further observations on the clinical significance and inheritance of the low-frequency platelet antigen HPA-28bw. Transfusion. 2016;56(4):873-7. doi: 10.1111/trf.13429.

  52. Ronzoni S, Keunen J, Arnold D, Smith J, Ryan G. Antenatal management of fetal neonatal alloimmune thrombocytopenia (FNAIT) and neonatal outcome according to the category of risk. Ultrasound Obstet Gynecol. 2016;48 (S1):357. doi: 10.1002/uog.17088.

  53. Wendel K, Akkök ÇA, Kutzsche S. Neonatal alloimmunethrombocytopaenia associated with maternal HLA antibodies. BMJ Case Rep. 2017;2017. pii: bcr-2016-218269. doi: 10.1136/bcr-2016-218269.

  54. Sen M, Koksal AC, Yuki K, Wang J, Springer TA. Ligand- and cation-induced structural alterations of the leukocyte integrin LFA-1. J Biol Chem. 2018;293(17):6565-77. doi: 10.1074/jbc.RA117.000710

  55. Poles A, Lucas G, Green F, Walser P, Davey S, Ridgwell K, et al. Neonatal alloimmune thrombocytopenia due to a new alloantigen Bl(a) defined by an Asp458Gly substitution in GPIIIa. Transfusion. 2019;59(1):396-404. doi: 10.1111/trf.14990.

  56. Solh Z, Breakey V, Murthy P, Smith JW, Arnold DM. Triplets with neonatal alloimmune thrombocytopenia due to antibodies against human platelet antigen 1a. Transfusion. 2016;56(5):1166-1170. doi: 10.1111/trf.13494.

  57. Chen L, Liu Z, Liu T, Ma X, Rao M, Wang Y, et al. Neonatal alloimmune thrombocytopenia caused by anti-HPA antibodies in pregnant Chinese women: a study protocol for a multicentre, prospective cohort trial. BMC Pregnan Childbirth. 2017;17(1):281. doi: 10.1186/s12884-017-1453-y.

  58. Van Der Lugt NM, Kamphuis MM, Paridaans NP, Figee A, Oepkes D, Walther, et al. Neonatal outcome in alloimmune thrombocytopenia after maternal treatment with intravenous immunoglobulin. Blood Transfus. 2015;13(1):66-71. doi: 10.2450/2014.0309-13.

  59. Tiller H, Husebekk A, Skogen B, Kjeldsen-Kragh J, Kjaer M. True risk of fetal/neonatal alloimmune thrombocytopenia in subsequent pregnancies: a prospective observational follow-up study. BJOG. 2016;123:738-44. doi: 10.1111/1471-0528.13343.

  60. Winkelhorst D, Oepkesa D and Lopriorec E. Fetal and neonatal alloimmune thrombocytopenia: evidence based antenatal and postnatal management strategies. Exp Rev Hematol. 2017;10 (8):729-37. doi: 10.1080/17474086.2017.1346471.

  61. Rossi KQ, Lehman KJ, O’Shaughnessy RW. Effects of antepartum therapy for fetal alloimmune thrombocytopenia on maternal lifestyle. J Matern Fetal Neonatal Med. 2016;29 (11): 1783-8. doi: 10.3109/14767058.2015.1063607.

  62. Paridaans NP, Kamphuis MM, TauneWikman A, Tiblad E, Van den Akker ES, Lopriore E, et al. Low-dose versus standard-dose intravenous immunoglobulin to prevent fetal intracranial hemorrhage in fetal and neonatal alloimmune thrombocytopenia: a randomized trial. Fetal Diagn Ther. 2015;38(2):147-53. doi:10.1159/00038090.




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