Management of Alloimmune Neonatal and
Antenatal Thrombocytopenia

Reznikoff-Etiévant, M.F.

doi:10.1159/000461874

Cited by 18 publications

(37 citation statements)

References 32 publications

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“…[4][5][6][7] The major risk of this disease is intracranial hemorrhage, which is associated with death and neurologic sequelae in affected neonates. [8][9][10][11][12] In addition, FNIT may also cause miscarriage, as has been reported from several independent research groups. 7,13 The recurrence rate of FNIT among subsequent platelet antigen-positive siblings is almost 100%, with the degree of thrombocytopenia generally being either similar or more severe.…”

Section: Introductionsupporting

confidence: 54%

Animal model of fetal and neonatal immune thrombocytopenia: role of neonatal Fc receptor in the pathogenesis and therapy

Chen

Lang

et al. 2010

Blood

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IntroductionFetal and neonatal immune thrombocytopenia (FNIT) is an alloimmune disorder that results from fetal platelet opsonization by maternal antibodies and subsequent platelet destruction. There are several platelet antigens that may have the potential to induce a maternal alloimmune response, particularly those polymorphisms within several extracellular domains of ␤3 integrin (eg, human platelet antigen-1a in whites and human platelet antigen-4b in Asians). [1][2][3] The incidence of FNIT has been estimated at 0.5-1.5 per 1000 live-born neonates, although the reported incidence varied in the different studies. [4][5][6][7] The major risk of this disease is intracranial hemorrhage, which is associated with death and neurologic sequelae in affected neonates. [8][9][10][11][12] In addition, FNIT may also cause miscarriage, as has been reported from several independent research groups. 7,13 The recurrence rate of FNIT among subsequent platelet antigen-positive siblings is almost 100%, with the degree of thrombocytopenia generally being either similar or more severe. 1,14 However, the immunopathogenic mechanisms of this disease are still largely unknown.Although several treatments, such as intravenous immunoglobulin G (IVIG), steroids, and fetal and neonatal platelet transfusions, have been used to manage FNIT, 1,8,[10][11][12]15 antenatal management of FNIT has not been standardized. 16 A safer and more effective therapy remains to be developed.The neonatal Fc receptor (FcRn) is a heterodimer consisting of a ␤2-microglobulin (␤2m) and a transmembrane ␣-chain that is homologous to the ␣-chain of major histocompatibility complex class I. 17,18 FcRn was first identified as the protein that mediated transfer of maternal, milk-borne immunoglobulin Gs (IgGs) across the neonatal rodent intestine. 19,20 It has been demonstrated that the binding of FcRn to IgG is strictly pH-dependent, 21,22 with binding occurring in slightly acidic environments (optimum pH 6.0) and no detectable binding at pH 7.4. Thus, FcRn binds to IgG in the neonatal gut lumen (low pH), transcytoses the bound IgG across intestinal epithelial cells, and releases it into the newborn blood circulation (pH 7.4). [21][22][23][24] Recent studies demonstrated that FcRn protected IgG from catabolic degradation. It is thought that during transcytosis, IgG is taken up into endosomes, which are acidified, allowing IgG to bind FcRn, whereas unbound IgG is degraded. 25,26 FcRn therefore plays an important role in extending IgG half-life in the blood circulation. 27 In several animal models of antibodymediated autoimmune diseases, 28-31 including autoimmune thrombocytopenia (idiopathic thrombocytopenic purpura [ITP]), therapeutic interventions that target FcRn have demonstrated to be effective in enhancing clearance of pathogenic antibodies. However, there are no reports available that indicate whether modulation of FcRn is a useful therapy for FNIT. FcRn was also reported to play an important role in the transplacental transport of IgG from the mother to the fe...

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Section: Introductionsupporting

confidence: 54%

Animal model of fetal and neonatal immune thrombocytopenia: role of neonatal Fc receptor in the pathogenesis and therapy

Chen

Lang

et al. 2010

Blood

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“…Immune-mediated cytopenias in the newborn are predominantly the result of maternal alloimmunization to cell surface antigens that may be restricted to certain cell types or part of the HLA loci (5,6). Maternal alloimmunization to HLA antigens occurs in about 40% of pregnancies; however, alloimmunization to platelet-and neutrophil-specific antigens occurs less frequently (14,15).…”

Section: Discussionmentioning

confidence: 99%

“…Maternal alloimmunization to HLA antigens occurs in about 40% of pregnancies; however, alloimmunization to platelet-and neutrophil-specific antigens occurs less frequently (14,15). Neonatal immune-mediated thrombocytopenia has been reported to occur in 111000 to 115,000 live births and is due to alloimmunization to the HPA-1 locus in 80% of reported cases and to other platelet-specific alloantigens and HLA antigens in the remainder of newborns (5,(16)(17)(18). Immune-mediated thrombocytopenia also occurs in infants born to preeclamptic mothers and may account for a significant amount of thrombocytopenia in these patients (19,20).…”

Section: Discussionmentioning

confidence: 99%

“…Immune-mediated thrombocytopenia and neutropenia represent a significant etiology for these cytopenias (3,4). These immune-mediated cytopenias may be characterized as alloimmune or autoimmune and result from increased amounts of IgG bound to the cell surface (direct) andlor identified in the serum (indirect) resulting in increased cell turnover (3,5,6). …”

mentioning

confidence: 99%

“…The laboratory evaluation of immune-mediated cytopenias depends upon the detection and quantitation of Ig against platelets and neutrophils compared with healthy controls (2,(4)(5)(6). However, the paucity of normal values for healthy, term infants hampers the interpretation and limits the diagnostic was not a significant difference in direct platelet-associated IgM, or indirect Ig to neutrophils or platelets.…”

mentioning

confidence: 99%

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