Management of alloimmune thrombocytopenia

Kanhai, H. H. H.; Porcelijn, Leendert; Engelfriet, C. P.; Reesink, H. W.; Panzer, Sarah E.; Ulm, Barbara; Goldman, Mindy; Bonacossa, Inés A.; Richard, Lucie; David, Michèle; Taaning, Ellen; Hedegaard, M; Kaplan, C.; Kiefel, V.; Meyer, Oliver; Salama, Abdulgabar; Morelati, Fernanda; Greppi, N.; Marconi, Maurizio; Tassis, Beatrice; Tsuno, Nelson H.; Takahashi, Keisuke; Oepkes, Dick; Kanhai, Humphrey H.H.; Osnes, Liv; Husebekk, Anne; Killie, Mette Kjær; Kjeldsen‐Kragh, Jens; Zupańska, B; Muñiz‐Díaz, Eduardo; Nogués, Núria; Parra, Johanna; Urbaniak, S. J.; Cameron, Alan

doi:10.1111/j.1423-0410.2007.00980.x

Cited by 32 publications

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“…FNIT is a devastating disease, and effective therapeutic intervention is currently limited and unstandardized (73). We previously demonstrated that maternal IVIG infusion ameliorated neonatal thrombocytopenia in the anti-β3 FNIT model (34).…”

Section: Discussionmentioning

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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Section: Discussionmentioning

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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“…Treatment options for fetal alloimmune thrombocytopenia include: (i) very preterm delivery at 32 weeks, accepting the risk of intracranial hemorrhage known to occur as early as 14-16 weeks' gestation; (ii) repeated maternal immunoglobulin G infusions; 25,26 (iii) repeated fetal platelet transfusions with a cumulative procedurerelated risk; and (iv) serial scans with the questionable option of late termination. 27,28 In order to assess efficacy of any treatment and to balance the risks and benefits of non-invasive and invasive approaches, the natural course of the disease should be known.…”

Section: Discussionmentioning

confidence: 99%

Fetal alloimmune thrombocytopenia and maternal intravenous immunoglobulin infusion

Giers

Wenzel²,

Stockschläder³

et al. 2010

Haematologica

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The online version of this article has a Supplementary Appendix. BackgroundDifferent therapeutic approaches have been used in fetal-neonatal alloimmune thrombocytopenia, but many centers administer immunoglobulin G infusions to the pregnant woman. We studied the effect of maternal antenatal immunoglobulin infusions on fetal platelet counts in pregnancies with fetal alloimmune thrombocytopenia. Design and MethodsWe retrospectively analyzed the clinical courses of fetuses with fetal alloimmune thrombocytopenia whose mothers were treated with immunoglobulin G infusions in a single center between 1999 and 2005. In a center-specific protocol, weekly maternal immunoglobulin G infusions were given to 25 pregnant women with previously affected neonates and four women with strong platelet antibodies, but no previous history of fetal alloimmune thrombocytopenia; before each infusion diagnostic fetal blood sampling was performed to determine fetal platelet counts and immunoglobulin G levels. ResultsThere were 30 fetuses with fetal alloimmune thrombocytopenia, confirmed by initial fetal blood sampling showing fetal platelet counts between 4¥10 9 /L and 130¥10 9 /L and antibodycoated fetal platelets using a glycoprotein specific assay. Despite weekly antenatal maternal immunoglobulin G infusions fetal platelet counts did not change significantly. Maternal and fetal immunoglobulin G levels, measured before every infusion, increased significantly with the number of maternal immunoglobulin G infusions. ConclusionsIn this group of fetuses with fetal alloimmune thrombocytopenia no consistent increase of fetal platelets was achieved as a result of regular maternal immunoglobulin G infusions.Key words: fetal alloimmune thrombocytopenia, maternal IgG infusion, intrauterine therapy. Haematologica. 201095(11):1921-1926. doi:10.3324/haematol.2010 This is an open-access paper. Citation: Giers G, Wenzel F, Stockschläder M, Riethmacher R, Lorenz H, and Tutschek B. Fetal alloimmune thrombocytopenia and maternal intravenous immunoglobulin infusion Fetal alloimmune thrombocytopenia and maternal intravenous immunoglobulin infusion

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“…Tidligere ble føtal blodprøvekontroll (trombocyttelling) og føtale trombocyttransfusjoner utført, men dette gjøres som hovedregel ikke i dag fordi prosedyren gir stor risiko for blødningskom-plikasjoner (11). I Norge er det per i dag sjelden at moren behandles med intravenøs injeksjon av polyklonalt immunglobulin før fødselen, men vi mener det er sannsynlig at dette i fremtiden vil bli anbefalt som standardbehandling hos kvinner som tidligere har født barn med hjerneblødning indusert av føtal/neonatal alloimmun trombocytopeni.…”

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Eriksen¹,

Husebekk²,

Fugelseth³

et al. 2013

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Management of alloimmune thrombocytopenia

Cited by 32 publications

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

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

Fetal alloimmune thrombocytopenia and maternal intravenous immunoglobulin infusion

Et nyfødt barn med petekkier

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