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Intravenous Immunoglobulin G Therapy in Fetal and Neonatal Alloimmune Thrombocytopenia

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Summary

Neonatal alloimmune thrombocytopenia (NAIT) is a rare disorder in the neonatal period, occurring in 1 in 2000 to 5000 births. The clinical syndrome of NAIT can be varied, but the resulting thrombocytopenia can be very severe and can result in serious haemorrhage in the fetus and neonate. At least 5 human platelet antigen systems have been described, and all have been implicated in cases of NAIT. Approximately 50% of platelet antigen-incompatible firstborn infants will be affected. The risk of recurrence in subsequent pregnancies is high, estimated at >75%, with the disease being either equally or more severe than in the first infant. Mortality in NAIT is estimated to be 10%, and is usually associated with intracranial haemorrhage. The incidence of intracranial haemorrhage is estimated to be approximately 14%, with approximately 25% occurring antenatally. In an effort to prevent these severe complications, therapy is usually instituted in infants with severe thrombocytopenia from NAIT. Treatment strategies have included appropriate, compatible platelet transfusion, corticosteroid use and exchange transfusion. However, success in treating immune-mediated thrombocytopenia with intravenous immunoglobulins (IVIg) has prompted the use of this therapy in fetuses and infants with NAIT. IVIg has demonstrated efficacy in both of these clinical situations. The literature concerning the use of IVIg, both ante-and post-natally, is reviewed, and treatment strategies for infants and fetuses affected by NAIT are discussed.

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References

  1. Mueller-Eckhardt C, Grubert A, Weisheit M, et al. 348 cases of suspected neonatal alloimmune thrombocytopenia. Lancet 1989 Feb; 1: 363–6

    Article  PubMed  CAS  Google Scholar 

  2. Burrows RF, Kelton JG. Fetal thrombocytopenia and its relation to maternal thrombocytopenia. N Engl J Med 1993; 329: 1463–6

    Article  PubMed  CAS  Google Scholar 

  3. von dem Borne AE, Décary F. Nomenclature of platelet-specific antigens [letter]. Transfusion 1990; 30: 477

    Article  Google Scholar 

  4. Goldberger A, Kolodziej M, Poncz M, et al. Effect of single amino acid substitutions on the formation of the P1A and Bak alloantigenic epitopes. Blood 1991 Aug; 78: 681–7

    PubMed  CAS  Google Scholar 

  5. Keifel V, Santoso S, Katzmann B, et al. The Bra/Brb alloantigen system on human platelets. Blood 1989 Jun; 73: 2219–23

    Google Scholar 

  6. Murata M, Furihata K, Ishida F, et al. Genetic and structural characterization of an amino acid dimorphism in glycoprotein Iba involved in platelet transfusion refractoriness. Blood 1992 Jun; 79: 3086–90

    PubMed  CAS  Google Scholar 

  7. Noris P, Simsek S, de Bruijne-Admiraal LG, et al. Maxa, a new low-frequency platelet-specific antigen localized on glycoprotein IIb, is associated with neonatal alloimmune thrombocytopenia. Blood 1995 Aug; 86(3): 1019–26

    PubMed  CAS  Google Scholar 

  8. Kiefel V, Vicariot M, Giovangrandi Y, et al. Alloimmunization against ly, a low-frequency antigen on platelet glycoprotein Ib/IX, as a cause of severe neonatal alloimmune thrombocytopenic purpura. Vox Sang 1995: 69: 250–4

    Article  PubMed  CAS  Google Scholar 

  9. Kroll H, Kiefel V, Santoso S, et al. Sra, a private platelet antigen on glycoprotein IIIa associated with neonatal alloimmune thrombocytopenia. Blood 1990 Dec; 76: 2296–302

    PubMed  CAS  Google Scholar 

  10. Kuijpers RW, Simsek S, Faber NM, et al. Single point mutation in human glycoprotein IIIa is associated with a new platelet-specific alloantigen (Mo) involved in neonatal alloimmune thrombocytopenia. Blood 1993; 81: 70–6

    PubMed  CAS  Google Scholar 

  11. Kekomäki R, Jouhikainen T, Ollikainen J, et al. A new platelet alloantigen, Tua, on glycoprotein IIIa associated with neonatal alloimmune thrombocytopenia in two families. Br J Haematol 1993; 83: 306–10

    Article  PubMed  Google Scholar 

  12. Borzini P, Riva M. Neonatal alloimmune thrombocytopenia in Italy. Vox Sang 1993; 65: 163–4

    Article  PubMed  CAS  Google Scholar 

  13. Waters AH. Platelets as immunogens. Blood Coagul Fibrinolysis 1992; 3: 637–41

    Article  PubMed  CAS  Google Scholar 

  14. Kim HO, Jin Y, Kickler TS, et al. Gene frequencies of the five major human platelet antigens in African American, white and Korean populations. Transfusion 1995; 35: 863–7

    Article  PubMed  CAS  Google Scholar 

  15. Kaplan C, Morel-Kopp MC, Kroll H, et al. HPA-5 (Bra) neonatal alloimmune thrombocytopenia: clinical and immunological analysis of 39 cases. Br J Haematol 1991; 78: 425–9

    Article  PubMed  CAS  Google Scholar 

  16. Panzer S, Auerbach L, Cechova E, et al. Maternal allo-immunization against fetal platelet antigens: a prospective study. Br J Haematol 1995; 90: 655–60

    Article  PubMed  CAS  Google Scholar 

  17. Bussel JB, Berkowitz RL, McFarland JG, et al. Antenatal treatment of neonatal alloimmune thrombocytopenia. N Engl J Med 1988 Nov; 319: 1374–8

    Article  PubMed  CAS  Google Scholar 

  18. Blanchette VS, Chen L, de Freidberg ZS, et al. Alloimmunization to the P1A1 platelet antigen: results of a prospective study. Br J Haematol 1990; 74: 209–15

    Article  PubMed  CAS  Google Scholar 

  19. Marzusch K, Fischer J, Dietl J, et al. Difficulties in the antenatal assessment of neonatal alloimmune thrombocytopenia. Acta Obstet Gynecol Scand 1993; 72: 583–5

    Article  PubMed  CAS  Google Scholar 

  20. Proulx C, Filion M, Goldman M, et al. Analysis of immunoglobulin class, IgG subclass and titre of HPA-1a antibodies in alloimmunized mothers giving birth to babies with or without neonatal alloimmune thrombocytopenia. Br J Haematol 1994; 87: 813–7

    Article  PubMed  CAS  Google Scholar 

  21. de Waal LP, van Dalen CM, Engelfriet CP, et al. Alloimmunization against the platelet-specific Zwa antigen, resulting in neonatal alloimmune thrombocytopenia or posttransfusion purpura, is associated with the supertypic DRw52 antigen including DR3 and DRw6. Hum Immunol 1986; 17: 45–53

    Article  PubMed  Google Scholar 

  22. Mueller-Eckhardt C, Mueller-Eckhardt G, Willen-Ohff H, et al. Immunogenicity of and immune response to the human platelet antigen Zwa is strongly associated with HLA-B8 and DR3. Tissue Antigens 1985; 26: 71–6

    Article  PubMed  CAS  Google Scholar 

  23. Reznikoff-Etievant MF. Management of alloimmune neonatal and antenatal thrombocytopenia. Vox Sang 1988; 55: 193–201

    Article  PubMed  CAS  Google Scholar 

  24. Kaplan C, Morel-Kopp MC, Clemenceau S, et al. Fetal and neonatal alloimmune thrombocytopenia: current trends in diagnosis and therapy. Transfus Med 1992; 2: 265–71

    Article  PubMed  CAS  Google Scholar 

  25. Bussel JB, Neonatal Immune Thrombocytopenia Study Group. Neonatal alloimmune thrombocytopenia (NAIT): a prospective case accumulation study [abstract]. Pediatr Res 1988; 23: 337A

    Article  Google Scholar 

  26. Kaplan C, Daffos F, Forestier F, et al. Management of alloimmune thrombocytopenia: antenatal diagnosis and in utero transfusion of maternal platelets. Blood 1988 Jul; 72: 340–3

    PubMed  CAS  Google Scholar 

  27. Herman JH, Jumbelic MI, Ancona RJ, et al. In utero cerebral hemorrhage in alloimmune thrombocytopenia. Am J Pediatr Hematol Oncol 1986; 8(4): 312–7

    Article  PubMed  CAS  Google Scholar 

  28. Burrows RF, Caco CC, Kelton JG. Neonatal alloimmune thrombocytopenia: spontaneous in utero intracranial hemorrhage. Am J Hematol 1988; 28: 98–102

    Article  PubMed  CAS  Google Scholar 

  29. Riley TF, Morrison S. Radiological case of the month. Arch Pediatr Adolesc Med 1994; 148: 951–2

    Article  PubMed  CAS  Google Scholar 

  30. Marzusch K, Schnaidt M, Dietl J, et al. High-dose immunoglobulin in the antenatal treatment of neonatal alloimmune thrombocytopenia: case report and review. Br J Obstet Gynaecol 1992; 99: 260–2

    Article  PubMed  CAS  Google Scholar 

  31. Johnson JM, Blanchette VS, McFarland JG, et al. Very early thrombocytopenia in neonatal alloimmune thrombocytopenia [abstract]. Am J Obstet Gynecol 1993; 68: 426

    Google Scholar 

  32. Kay HH, Hage ML, Kurtzberg J, et al. Alloimmune thrombocytopenia may be associated with systemic disease. Am J Obstet Gynecol 1992; 166: 110–1

    PubMed  CAS  Google Scholar 

  33. Giltay JC, Brinkman HM, von dem Borne AE, et al. Expression of the alloantigen Zwa (or P1 A1) on human vascular smooth muscle cells and foreskin fibroblasts: a study on normal individuals and a patient with Glanzmann’s thrombasthenia. Blood 1989 Aug; 74(3): 965–70

    PubMed  CAS  Google Scholar 

  34. Sidiropoulos D, Straume B. The treatment of neonatal isoimmune thrombocytopenia with intravenous immunoglobulin (IgG i.V.). Blut 1984; 48: 383–6

    Article  PubMed  CAS  Google Scholar 

  35. Suarez CR, Anderson C. High-dose intravenous gammaglobulin (IVG) in neonatal immune thrombocytopenia. Am J Hematol 1987; 26: 247–53

    Article  PubMed  CAS  Google Scholar 

  36. Massey GV, McWilliams NB, Mueller DG, et al. Intravenous immunoglobulin in treatment of neonatal isoimmune thrombocytopenia. J Pediatr 1987; 111: 133–5

    Article  PubMed  CAS  Google Scholar 

  37. Lee A, Permezel M, Dennington P, et al. Neonatal alloimmune thrombocytopenia: a case report and a review of the literature. Aust NZ J Obstet Gynaecol 1993; 33: 420–3

    Article  CAS  Google Scholar 

  38. Pietz J, Kiefel V, Sontheimer D, et al. High-dose intravenous gammaglobulin for neonatal alloimmune thrombocytopenia in twins. Acta Paediatr Scand 1991; 80: 129–32

    Article  PubMed  CAS  Google Scholar 

  39. Beck R, Reid DM, Lazarte R. Intravenous gammaglobulin therapy for neonatal alloimmune thrombocytopenia. Am J Peri-natol 1988; 5: 79–82

    Article  CAS  Google Scholar 

  40. Mueller-Eckhardt C, Kiefel V, Grubert A. High-dose IgG treatment for neonatal alloimmune thrombocytopenia. Blut 1989; 59: 145–6

    Article  PubMed  CAS  Google Scholar 

  41. Forestier F, Daffos F, Galacteros F, et al. Hematological values of 163 normal fetuses between 18 and 30 weeks of gestation. Pediatr Res 1986; 20: 342–6

    Article  PubMed  CAS  Google Scholar 

  42. Waters AH, Ireland R, Mibashan RS, et al. Fetal platelet transfusions in the management of alloimmune thrombocytopenia [abstract]. Thromb Haemost 1987; 58: 323

    Google Scholar 

  43. Nicolini U, Tannirandorn Y, Gonzalez P, et al. Continuing controversy in alloimmune thrombocytopenia: fetal hyper-immunoglobulinemia fails to prevent thrombocytopenia. Am J Obstet Gynecol 1990; 163: 1144–6

    PubMed  CAS  Google Scholar 

  44. Murphy MF, Waters AH, Doughty HA, et al. Antenatal management of fetomaternal alloimmune thrombocytopenia — report of 15 affected pregnancies. Transfus Med 1994; 4: 281–92

    Article  PubMed  CAS  Google Scholar 

  45. Kaplan C. Prenatal treatment in neonatal alloimmune thrombocytopenia. Curr Stud Hematol Blood Transfus 1988; 55: 142–7

    PubMed  Google Scholar 

  46. Lynch L, Bussel JB, McFarland JG, et al. Antenatal treatment of alloimmune thrombocytopenia. Obstet Gynecol 1992; 80: 67–71

    PubMed  CAS  Google Scholar 

  47. Shwe KH, Love EM, Lieberman BA, et al. High-dose intravenous immunoglobulin in the prenatal management of neonatal alloimmune thrombocytopenia. Clin Lab Haematol 1991; 13: 75–9

    Article  PubMed  CAS  Google Scholar 

  48. Poulain P, Kaplan C, Leberre C, et al. Alloimmune thrombocytopenia: in utero treatment by high doses of intravenous gamma globulins. Fetal Diagn Ther 1992; 7: 144–6

    Article  PubMed  CAS  Google Scholar 

  49. Dickinson JE, Marshall LR, Phillips JM, et al. Antenatal diagnosis and management of fetomaternal alloimmune thrombocytopenia. Am J Perinatol 1995; 12: 333–5

    Article  PubMed  CAS  Google Scholar 

  50. Nathan FE, Herman JH, McFarland JG, et al. Anti-Baka neonatal alloimmune thrombocytopenia: possible prevention by intravenous immunoglobulin. Pediatr Hematol Oncol 1994; 11: 325–9

    Article  PubMed  CAS  Google Scholar 

  51. Mir N, Samson D, House MJ, et al. Failure of antenatal high-dose immunoglobulin to improve fetal platelet count in neonatal allo-immune thrombocytopenia. Vox Sang 1988; 55: 188–9

    Article  PubMed  CAS  Google Scholar 

  52. Murphy MF, Metcalfe P, Waters AH, et al. Antenatal management of severe feto-maternal alloimmune thrombocytopenia: HLA incompatibility may affect responses to fetal platelet transfusions. Blood 1993 Apr; 81: 2174–9

    PubMed  CAS  Google Scholar 

  53. Pearlman SA, Meek RS, Cowchock FS, et al. Neonatal alloimmune thrombocytopenia after maternal immunization with parental mononuclear cells: successful treatment with intravenous gamma globulin. Am J Perinatol 1992; 9: 448–51

    Article  PubMed  CAS  Google Scholar 

  54. Kroll H, Keifel V, Giers G, et al. Maternal intravenous immunoglobulin treatment does not prevent intracranial haemorrhage in fetal alloimmune thrombocytopenia. Transfus Med 1994; 4: 293–6

    Article  PubMed  CAS  Google Scholar 

  55. Reese J, Raghuveer TS, Dennington PM, et al. Breast feeding in neonatal alloimmune thrombocytopenia. J Paediatr Child Health 1994; 30: 447–9

    Article  PubMed  CAS  Google Scholar 

  56. Zimmerman R, Huch A. In-utero fetal therapy with immunoglobulin for alloimmune thrombocytopenia [letter]. Lancet 1992 Sep; 340: 606

    Article  Google Scholar 

  57. Weiner E, Zosmer N, Bajoria R, et al. Direct fetal administration of immunoglobulins: another disappointing therapy in alloimmune thrombocytopenia. Fetal Diagn Ther 1994; 9: 159–64

    Article  PubMed  CAS  Google Scholar 

  58. Kaplan C, Daffos F, Forestier F, et al. Management of fetal and neonatal alloimmune thrombocytopenia. Vox Sang 1994; 67 (3 Suppl.): 85–8

    Article  PubMed  Google Scholar 

  59. Blanchette VS. Neonatal alloimmune thrombocytopenia: a clinical perspective. Curr Stud Hematol Blood Transfus 1988; 54: 112–26

    PubMed  Google Scholar 

  60. Reesink HW, Engelfriet CP. Prenatal management of fetal alloimmune thrombocytopenia [International Forum, editorial]. Vox Sang 1993; 65: 180–9

    Article  Google Scholar 

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Dunsmore, K.P. Intravenous Immunoglobulin G Therapy in Fetal and Neonatal Alloimmune Thrombocytopenia. BioDrugs 8, 265–272 (1997). https://doi.org/10.2165/00063030-199708040-00003

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