Antenatal treatment of fetal alloimmune thrombocytopenia: a current perspective

Vinograd, Cheryl A.; Bussel, James B.

doi:10.3324/haematol.2010.030148

Cited by 31 publications

(25 citation statements)

References 28 publications

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“…Today, maternally administered IVIG is generally considered to be highly successful in preventing ICH, the true goal of antenatal management, even when failing to keep the fetal platelet count within a safe range. In keeping with previous studies (Vinogard & Bussel, 2010;Kamphuis & Oepkes, 2011;van der Lugt et al, 2015), the response rate to IVIG in our study was only 50%, when defined as neonatal platelet counts remaining <50 9 10 9 /l. Furthermore, two of these non-responders were diagnosed with ICH, a finding also reported before (Berkowitz et al, 2006).…”

Section: Discussionsupporting

confidence: 67%

“…Non-or minimal-invasive strategies with maternally administrated intravenous gammaglobulin (IVIG) are regarded as the primary management option although a substantial proportion of fetuses (up to 55%) seem not to respond to IVIG treatment, with platelet counts remaining below 50 9 10 9 /l (Vinogard & Bussel, 2010;Kamphuis & Oepkes, 2011;van der Lugt et al, 2015). On the other hand, current laboratory techniques may miss some clinically evident cases, leaving the subsequent pregnancies without required therapy (Bussel et al, 2005).…”

Section: Fetal and Neonatal Alloimmune Thrombocytopenia (Fnait)mentioning

confidence: 99%

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Maternal HLA genotyping is not useful for predicting severity of fetal and neonatal alloimmune thrombocytopenia

et al. 2016

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SummaryLack of reliable laboratory parameters is the main challenge in the management of fetal and neonatal alloimmune thrombocytopenia (FNAIT). Despite the long-known association between the HLA-DRB3*01:01 allele and human platelet antigen 1a (HPA-1a) alloimmunisation, maternal human leucocyte antigen (HLA) typing has been of little clinical value. Recently, other DRB3 allele variants have been suggested to predict the severity of FNAIT. In this nationwide population-based retrospective cohort study, we performed extensive HLA typing of 96 women, accounting for 87% of our cohort of 110 families with confirmed or possible HPA-1a-immunisation. The HLA type was compared with anti-HPA-1a levels, severity of neonatal disease and responsiveness to maternally administrated intravenous gammaglobulin (IVIG). HLA haplotypes were constructed to investigate further HLA associations. Despite significantly lower anti-HPA-1a levels in DRB3*01:01-negative women, the carrier status of this particular allele could not be used to confirm or rule out FNAIT in the absence of detectable antibodies. In the haplotype analysis, the DRB3*01:01 allele was the actual factor associated with FNAIT. No other HLA allele was shown to be of additional value as a predictor of severe FNAIT or non-responsiveness to IVIG treatment. Thus, HLA genotyping was not found useful in differentiating high-and low-risk pregnancies or in guiding antenatal treatment in affected families.

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Section: Discussionsupporting

confidence: 67%

Section: Fetal and Neonatal Alloimmune Thrombocytopenia (Fnait)mentioning

confidence: 99%

Maternal HLA genotyping is not useful for predicting severity of fetal and neonatal alloimmune thrombocytopenia

et al. 2016

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“…8,15,16 These treatments are expensive, limited by access to IVIg, and not without side effects, and therefore some authors recommend the use of a stratified treatment approach based on the severity of previously affected pregnancies (the only clear predictor of disease severity). [16][17][18] Although the rate of fetal ICH in pregnancies undergoing immunomodulatory treatment appears low, it is clear that this is not accompanied by a consistent rise in platelet count in the fetus. 19,20 It may be that IVIg somehow lessens the risk of bleeding even in the absence of a rise in platelet count but it is also possible that the reduction of ICH comes with the increased care provided to the pregnant woman.…”

Section: Introductionmentioning

confidence: 99%

Recombinant HPA-1a antibody therapy for treatment of fetomaternal alloimmune thrombocytopenia: proof of principle in human volunteers

Ghevaert

Herbert

Hawkins

et al. 2013

Blood

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Key Points• Recombinant antibody B2G1Dnab protects platelets from destruction by anti-HPA-1a in the circulation of HPA-1a1b human volunteers.• B2G1Dnab is a potential therapeutic agent for antenatal treatment of fetomaternal alloimmune thrombocytopenia due to HPA-1a antibodies.Fetomaternal alloimmune thrombocytopenia, caused by the maternal generation of antibodies against fetal human platelet antigen-1a (HPA-1a), can result in intracranial hemorrhage and intrauterine death. We have developed a therapeutic human recombinant high-affinity HPA-1a antibody (B2G1Dnab) that competes for binding to the HPA-1a epitope but carries a modified constant region that does not bind to Fcg receptors. In vitro studies with a range of clinical anti-HPA-1a sera have shown that B2G1Dnab blocks monocyte chemiluminescence by >75%. In this firstin-man study, we demonstrate that HPA-1a1b autologous platelets (matching fetal phenotype) sensitized with B2G1Dnab have the same intravascular survival as unsensitized platelets (190 hours), while platelets sensitized with a destructive immunoglobulin G1 version of the antibody (B2G1) are cleared from the circulation in 2 hours. Mimicking the situation in fetuses receiving B2G1Dnab as therapy, we show that platelets sensitized with a combination of B2G1 (representing destructive HPA-1a antibody) and B2G1Dnab survive 3 times as long in circulation compared with platelets sensitized with B2G1 alone. This confirms the therapeutic potential of B2G1Dnab. The efficient clearance of platelets sensitized with B2G1 also opens up the opportunity to carry out studies of prophylaxis to prevent alloimmunization in HPA-1a-negative mothers. (Blood. 2013;122(3):313-320)

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“…About 20% of the newborns remain severely thrombocytopenic despite treatment of the mother with intravenous immunoglobulin and steroids. 12,17 Submitted November 20, 2012; accepted April 26, 2013. Prepublished online as Blood First Edition paper, May 3, 2013; DOI 10.1182/blood-2012-11-468561.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of HPA-1a alloantibody-mediated platelet destruction by a deglycosylated anti–HPA-1a monoclonal antibody in mice: toward targeted treatment of fetal-alloimmune thrombocytopenia

Bakchoul

Greinacher²,

Sachs

et al. 2013

Blood

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Antenatal treatment of fetal alloimmune thrombocytopenia: a current perspective

Cited by 31 publications

References 28 publications

Maternal HLA genotyping is not useful for predicting severity of fetal and neonatal alloimmune thrombocytopenia

Maternal HLA genotyping is not useful for predicting severity of fetal and neonatal alloimmune thrombocytopenia

Recombinant HPA-1a antibody therapy for treatment of fetomaternal alloimmune thrombocytopenia: proof of principle in human volunteers

Inhibition of HPA-1a alloantibody-mediated platelet destruction by a deglycosylated anti–HPA-1a monoclonal antibody in mice: toward targeted treatment of fetal-alloimmune thrombocytopenia

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