Prospective epidemiologic study of the outcome and cost‐effectiveness of antenatal screening to detect neonatal alloimmune thrombocytopenia due to anti‐HPA‐1a

Turner, Marc; Bessos, Hagop; Fagge, Timothy; Harkness, Mairi; Rentoul, Frances; Seymour, J; Wilson, David; Gray, I.; Ahya, R.; Cairns, John; Urbaniak, S. J.

doi:10.1111/j.1537-2995.2005.00645.x

Cited by 123 publications

(157 citation statements)

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“…Several groups have published calculations of costs and potential benefits of screening and intervention, all coming to the same conclusion that such programs are likely cost-effective. [5][6][7][20][21][22] The main reason for cost-effectiveness, despite large-scale testing and, in the case of IVIG, expensive treatment, is the fact that the disease burden and costs for a child with lifelong severe neurologic damage from ICH is excessive.…”

Section: Perinatal Mortality and Neonatal Morbiditymentioning

confidence: 99%

Incidence and Consequences of Neonatal Alloimmune Thrombocytopenia: A Systematic Review

Kamphuis¹,

Paridaans²,

Porcelijn

et al. 2014

Pediatrics

102

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BACKGROUND: Neonatal alloimmune thrombocytopenia (NAIT) is a potentially devastating disease that may lead to intracranial hemorrhage in the fetus or neonate, often with death or major neurologic damage. There are no routine screening programs for NAIT, preventive measures are taken only in a subsequent pregnancy. To estimate the population incidence of NAIT and its consequences, we conducted a review of the literature. Our results may aid in the design of a screening program.METHODS: An electronic literature search included Medline, Embase, Cochrane database and references of retrieved articles. Eligible for inclusion were all prospective studies aimed at diagnosing NAIT in a general, nonselected newborn population, with sufficient information on platelet count at birth, bleeding complications, and treatment. Titles and abstracts were reviewed, followed by review of full text publications. Studies were independently assessed by 2 reviewers for methodologic quality. Disagreements were resolved by consensus, including a third reviewer.

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Section: Perinatal Mortality and Neonatal Morbiditymentioning

confidence: 99%

Incidence and Consequences of Neonatal Alloimmune Thrombocytopenia: A Systematic Review

Kamphuis¹,

Paridaans²,

Porcelijn

et al. 2014

Pediatrics

102

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“…[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.…”

Section: Introductionmentioning

confidence: 99%

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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“…The human platelet antigen (HPA)-1 system on the platelet b 3 integrin subunit is the clinically most relevant one in Caucasoids, [1,2] causing fetomaternal alloimmune thrombocytopenia (FMAIT) in 1 in 1200 neonates and refractoriness to transfused platelets [3,4]. The difference between the major and minor allele is due to the non-synonymous single-nucleotide polymorphism rs5918 in the ITGB3 gene encoding a Leu (HPA-1a) or a Pro (HPA-1b) at position 33 (http://www.…”

Section: Introductionmentioning

confidence: 99%

Immunologic and structural analysis of eight novel domain-deletion β₃integrin peptides designed for detection of HPA-1 antibodies

Stafford¹,

Ghevaert²,

Campbell³

et al. 2008

J Thromb Haemost

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WH. Immunologic and structural analysis of eight novel domain-deletion b 3 integrin peptides designed for detection of HPA-1 antibodies. J Thromb Haemost 2008; 6: 366-75.See also Stafford P, Garner SF, Huiskes E, Kaplan C, Kekomaki R, Santoso S, Tsuno NH, Watkins NA, Ouwehand WH. Three novel b3 domaindeletion peptides for the sensitive and specific detection of HPA-4 and six low frequency b3-HPA antibodies. This issue, pp 376-83.Summary. Background: The single-nucleotide polymorphism (SNP) rs5918 in the ITGB3 gene defines the human platelet antigen-1 (HPA-1) system encoding a Leu (HPA-1a) or Pro (HPA-1b) at position 33. HPA-1 antibodies are clinically the most relevant in the Caucasoid population, but detection currently requires a IIb b 3 integrin from the platelets of HPAgenotyped donors. Objectives: We set out to define the b 3 integrin domains required for HPA-1a antibody binding and produce recombinant soluble b 3 peptides for HPA-1 antibody detection. Methods: We designed two sets (1a and 1b) of four soluble b 3 domain-deletion peptides (DSDL, DbA, PSIHybrid, PSI), informed by crystallography studies and computer modeling. The footprints of three human HPA-1a-specific phage antibodies were defined by analyzing binding patterns to the b 3 peptides and canine platelets, and models of antibodyantigen interfaces were derived. Specificity and sensitivity for HPA-1a detection were assessed using sera from 140 cases of fetomaternal alloimmune thrombocytopenia (FMAI-T). Results: Fusion of recombinant proteins to calmodulin resulted in high-level expression in Drosophila S2 cells of all eight b 3 peptides. Testing of FMAIT samples indicated that DbA-Leu33 is the superior peptide for HPA-1a antibody detection, with 96% sensitivity and 95% specificity. The existence of type I and II categories of HPA-1a antibodies was confirmed by the study of HPA-1a phage antibody footprints and the reactivity pattern of clinical samples with the four b 3 -Leu33 peptides, but there was no correlation between antibody category and clinical severity of FMAIT. Conclusions: Soluble recombinant b 3 peptides can be used for detection of clinical HPA-1a antibodies.

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Prospective epidemiologic study of the outcome and cost‐effectiveness of antenatal screening to detect neonatal alloimmune thrombocytopenia due to anti‐HPA‐1a

Cited by 123 publications

References 35 publications

Incidence and Consequences of Neonatal Alloimmune Thrombocytopenia: A Systematic Review

Incidence and Consequences of Neonatal Alloimmune Thrombocytopenia: A Systematic Review

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

Immunologic and structural analysis of eight novel domain-deletion β₃integrin peptides designed for detection of HPA-1 antibodies

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Prospective epidemiologic study of the outcome and cost‐effectiveness of antenatal screening to detect neonatal alloimmune thrombocytopenia due to anti‐HPA‐1a

Cited by 123 publications

References 35 publications

Incidence and Consequences of Neonatal Alloimmune Thrombocytopenia: A Systematic Review

Incidence and Consequences of Neonatal Alloimmune Thrombocytopenia: A Systematic Review

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

Immunologic and structural analysis of eight novel domain-deletion β3integrin peptides designed for detection of HPA-1 antibodies

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Immunologic and structural analysis of eight novel domain-deletion β₃integrin peptides designed for detection of HPA-1 antibodies