Very early intracranial haemorrhage in alloimmune fetal thrombocytopenia

Giovangrandi, Yves; Daffos, F.; Kaplan, C.; Forestier, F.; Aleese, J. Mac; Moirot, M.

doi:10.1016/0140-6736(90)91842-x

Cited by 95 publications

(50 citation statements)

References 7 publications

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“…One in 4 babies born to HPA-1a-immunized mothers have fewer than 20 × 10 9 platelets/l (5-10), which leads to intracranial hemorrhage (ICH) in 10% to 20% of all cases with fetomaternal alloimmune thrombocytopenia (FMAIT), from 16 weeks of pregnancy through the postnatal period (8,11,12). There is no consensus on the most effective antenatal therapy for FMAIT (13).…”

Section: Introductionmentioning

confidence: 99%

Developing recombinant HPA-1a–specific antibodies with abrogated Fcγ receptor binding for the treatment of fetomaternal alloimmune thrombocytopenia

Ghevaert

Wilcox²,

Fang³

et al. 2008

J. Clin. Invest.

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Fetomaternal alloimmune thrombocytopenia (FMAIT) is caused by maternal generation of antibodies specific for paternal platelet antigens and can lead to fetal intracranial hemorrhage. A SNP in the gene encoding integrin β3 causes a clinically important maternal-paternal antigenic difference; Leu33 generates the human platelet antigen 1a (HPA-1a), whereas Pro33 generates HPA-1b. As a potential treatment to prevent fetal intracranial hemorrhage in HPA-1a alloimmunized pregnancies, we generated an antibody that blocks the binding of maternal HPA-1a-specific antibodies to fetal HPA-1a1b platelets by combining a high-affinity human HPA-1a-specific scFv (B2) with an IgG1 constant region modified to minimize Fcγ receptor-dependent platelet destruction (G1Δnab). B2G1Δnab saturated HPA-1a + platelets and substantially inhibited binding of clinical HPA-1a-specific sera to HPA-1a + platelets. The response of monocytes to B2G1Δnab-sensitized platelets was substantially less than their response to unmodified B2G1, as measured by chemiluminescence. In addition, B2G1Δnab inhibited chemiluminescence induced by B2G1 and HPA-1a-specific sera. In a chimeric mouse model, B2G1 and polyclonal Ig preparations from clinical HPA-1a-specific sera reduced circulating HPA-1a + platelets, concomitant with transient thrombocytopenia. As the Δnab constant region is uninformative in mice, F(ab′) 2 B2G1 was used as a proof of principle blocking antibody and prevented the in vivo platelet destruction seen with B2G1 and polyclonal HPA-1a-specific antibodies. These results provide rationale for human clinical studies.

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Section: Introductionmentioning

confidence: 99%

Developing recombinant HPA-1a–specific antibodies with abrogated Fcγ receptor binding for the treatment of fetomaternal alloimmune thrombocytopenia

Ghevaert

Wilcox²,

Fang³

et al. 2008

J. Clin. Invest.

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“…Prior to birth, as early as 20-24 weeks of gestation, NAIT may cause ICH with the potential for porencephaly or intrauterine death. 5 The risk of clinically significant bleeding in infants with NAIT is higher than in those with similar platelet counts due to maternal ITP or maternal SLE, making the recommendations for intervention more aggressive.…”

Section: Neonatal Alloimmune Thrombocytopeniamentioning

confidence: 99%

Management of Bleeding Disorders in Children

Manno

2005

Hematology

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“…We have identified 16 cases of ICH reported in the literature, where the bleeding was diagnosed in utero and the gestational age at the time of diagnosis was stated. Four (25%) of the cases were diagnosed before 29 weeks (weeks 20, 21, 24 and 28) [23,29,30]. The majority of cases (75%) were diagnosed after 30 weeks (range: 31-37 weeks; mean: 33.5 weeks) [3,[30][31][32][33][34][35][36][37], but the time of diagnosis does not, of course, equate to the time of bleeding onset; the bleeding may occur some time before diagnosis.…”

Section: Perspectivementioning

confidence: 99%

“…The glycoprotein IIIa is present in the platelet membrane from week 16 of gestation [22], and immunization may occur as early as at week 16-20 [23,24]. In several aspects, FNAIT is the platelet counterpart to hemolytic disease of the newborn (HDN).…”

Section: Time Of Immunizationmentioning

confidence: 99%