Management and outcome of 200 cases of fetomaternal alloimmune thrombocytopenia

Ghevaert, Cédric; Campbell, Kate; Walton, J.; Smith, Graham; Allen, Dave; Williamson, Lorna M.; Ouwehand, Willem H.; Ranasinghe, E.

doi:10.1111/j.1537-2995.2007.01208.x

Cited by 155 publications

(165 citation statements)

References 48 publications

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“…Either purified polyclonal human anti-HPA 1a immunoglobulin G or recombinant human HPA 1a antibodies could be used for this purpose. 27 We and others have previously reported that anti-HPA 1a antibody levels decrease throughout pregnancy in women who have had a previous pregnancy. 9,[28][29][30] The fact that the levels of antibodies to the rubella antigen were stable during pregnancy disproves the hypothesis that the decrease in anti-HPA 1a antibody levels could be due to the normal hemodilution that occurs during pregnancy.…”

Section: Discussionmentioning

confidence: 99%

A prospective study of maternal anti-HPA 1a antibody level as a potential predictor of alloimmune thrombocytopenia in the newborn

Killie¹,

Husebekk²,

et al. 2008

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Section: Discussionmentioning

confidence: 99%

A prospective study of maternal anti-HPA 1a antibody level as a potential predictor of alloimmune thrombocytopenia in the newborn

Killie¹,

Husebekk²,

et al. 2008

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“…FMAIT results from transplacental transfer of maternal antibodies that develop in response to alloimmunization against paternal human platelet antigens (HPAs) expressed on fetal platelets. The HPA-1a antigen is responsible for the great majority of cases of severe FMAIT in individuals of mixed European descent (23). FMAIT is uncommon (affecting approximately 1 in 1,000 births), but it is the most important cause of severe fetal/neonatal thrombocytopenia and is associated with substantial morbidity and mortality due to intracranial hemorrhage, the risk of which is higher if a previous sibling was similarly affected (24).…”

Section: Fc-fcr Interactions In Neonatal Alloimmune Thrombocytopeniamentioning

confidence: 99%

Fc receptors in immune thrombocytopenias: a target for immunomodulation?

Psaila

Bussel²

2008

J. Clin. Invest.

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“…The incidence of FNIT has been estimated at 0.5-1.5 per 1,000 liveborn neonates (1)(2)(3)(4). This number, however, does not include miscarriages caused by the disease, since the rate of fetal mortality in affected pregnant women has not been adequately studied, although miscarriage has been reported by several groups (9)(10)(11)(12)(13). Currently, the mechanisms leading to miscarriage in these women and the therapies to prevent this devastating consequence are unknown.…”

Section: Introductionmentioning

confidence: 99%

The maternal immune response to fetal platelet GPIbα causes frequent miscarriage in mice that can be prevented by intravenous IgG and anti-FcRn therapies

et al. 2011

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Fetal and neonatal immune thrombocytopenia (FNIT) is a severe bleeding disorder caused by maternal antibody-mediated destruction of fetal/neonatal platelets. It is the most common cause of severe thrombocytopenia in neonates, but the frequency of FNIT-related miscarriage is unknown, and the mechanism(s) underlying fetal mortality have not been explored. Furthermore, although platelet αIIbβ3 integrin and GPIbα are the major antibody targets in immune thrombocytopenia, the reported incidence of anti-GPIbα-mediated FNIT is rare. Here, we developed mouse models of FNIT mediated by antibodies specific for GPIbα and β3 integrin and compared their pathogenesis. We found, unexpectedly, that miscarriage occurred in the majority of pregnancies in our model of anti-GPIbα-mediated FNIT, which was far more frequent than in anti-β3-mediated FNIT. Dams with anti-GPIbα antibodies exhibited extensive fibrin deposition and apoptosis/necrosis in their placentas, which severely impaired placental function. Furthermore, anti-GPIbα (but not anti-β3) antiserum activated platelets and enhanced fibrin formation in vitro and thrombus formation in vivo. Importantly, treatment with either intravenous IgG or a monoclonal antibody specific for the neonatal Fc receptor efficiently prevented anti-GPIbα-mediated FNIT. Thus, the maternal immune response to fetal GPIbα causes what we believe to be a previously unidentified, nonclassical FNIT (i.e., spontaneous miscarriage but not neonatal bleeding) in mice. These results suggest that a similar pathology may have masked the severity and frequency of human anti-GPIbα-mediated FNIT, but also point to possible therapeutic interventions.

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Management and outcome of 200 cases of fetomaternal alloimmune thrombocytopenia

Abstract: HPA-1a antibodies are most commonly implicated in severe thrombocytopenia but HPA-5b and HPA-15b antibodies can also result in poor outcome. Postnatal transfusion management is extremely variable, and fetal transfusions are associated with significant morbidity and mortality.

Cited by 155 publications

References 48 publications

A prospective study of maternal anti-HPA 1a antibody level as a potential predictor of alloimmune thrombocytopenia in the newborn

A prospective study of maternal anti-HPA 1a antibody level as a potential predictor of alloimmune thrombocytopenia in the newborn

Fc receptors in immune thrombocytopenias: a target for immunomodulation?

The maternal immune response to fetal platelet GPIbα causes frequent miscarriage in mice that can be prevented by intravenous IgG and anti-FcRn therapies

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