Reconsidering fetal and neonatal alloimmune thrombocytopenia with a focus on screening and prevention

Skogen, Bjøŕn; Killie, Mette Kjær; Kjeldsen‐Kragh, Jens; Ahlén, Maria Therese; Tiller, Heidi; Stuge, Tor B.; Husebekk, Anne

doi:10.1586/ehm.10.49

Cited by 35 publications

(29 citation statements)

References 58 publications

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“…In a recent assessment of prospective studies on screening for HPA-1a alloimmunization including 176,000 low-risk pregnancies, it was concluded that screening of all pregnancies combined with antenatal treatment may reduce mortality and morbidity associated with FNAIT but that large-scale screening studies are needed to evaluate the effect of currently used interventions 37. Introduction of antenatal screening for FNAIT was considered in relation to the revised World Health Organization screening criteria,134 and it was concluded that the screening criteria were fulfilled 135. The ongoing Polish PREVFNAIT screening study is primarily undertaken to demonstrate the feasibility of implementing antenatal HPA-1 screening as a national routine later.…”

Section: Screeningmentioning

confidence: 99%

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Current perspectives on fetal and neonatal alloimmune thrombocytopenia – increasing clinical concerns and new treatment opportunities

Tiller

Husebekk

Ahlén

et al. 2017

IJWH

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Differences in platelet type between the fetus and the mother can lead to maternal immunization and destruction of the fetal platelets, a condition named fetal and neonatal alloimmune thrombocytopenia (FNAIT). FNAIT is reported to occur in ~1 per 1,000 live born neonates. The major risk is intracranial hemorrhage in the fetus or newborn, which is associated with severe neurological complications or death. Since no countries have yet implemented a screening program to detect pregnancies at risk, the diagnosis is typically established after the birth of a child with symptoms. Reports on broader clinical impact have increased clinical concern and awareness. Along with new treatment options for FNAIT, the debate around antenatal screening to detect pregnancies at risk of FNAIT has been revitalized.

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Section: Screeningmentioning

confidence: 99%

“…Those in favor of screening state that randomized controlled trials would be unethical to perform and that we will never gain this knowledge without first introducing screening 135,136…”

Section: Screeningmentioning

confidence: 99%

Current perspectives on fetal and neonatal alloimmune thrombocytopenia – increasing clinical concerns and new treatment opportunities

Tiller

Husebekk

Ahlén

et al. 2017

IJWH

Self Cite

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“…Finally, alloimmunization may occur naturally during pregnancy and cause a host of pathological conditions for the fetus as well as consequences for subsequent conception. The neonatal conditions linked to alloimmunization include fetal and neonatal alloimmune thrombocytopenia [126,127], fetal and neonatal hemolytic anemia [128], alloimmune neonatal neutropenia [129], hydrops fetalis [130], neonatal hemochromatosis [131], biliary atresia [132], and neonatal glomerulopathy [133]. Alloimmunization was also proposed to at least partially explain implantation failure, recurrent pregnancy loss and pre-eclampsia/eclampsia [134,135] as well as inflammatory lesions of the placental villi during pregnancy [136].…”

Section: Discussionmentioning

confidence: 99%

Genetics of Transfusion Recipient Alloimmunization: Can Clues from Susceptibility to Autoimmunity Pave the Way?

Tatari-Calderone

Luban

Vukmanović

2014

Transfus Med Hemother

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The search for genetic determinants of alloimmunization in sickle cell disease transfusion recipients was based on two premises: i) that polymorphisms responsible for stronger immune and/or inflammatory responses and hemoglobin β^S mutation were co-selected by malaria; and ii) that stronger responder status contributes to development of lupus. We found a marker of alloimmunization in the gene encoding for Ro52 protein, also known as Sjögren syndrome antigen 1 (SSA1) and TRIM21. Surprisingly, the nature of the association was opposite of that with lupus; the same variant of a polymorphism (rs660) that was associated with lupus incidence was also associated with induction of tolerance to red blood cell antigens during early childhood. The dual function of Ro52 can explain this apparent contradiction. We propose that other lupus/autoimmunity susceptibility loci may reveal roles of additional molecules in various aspects of alloimmunization induced by transfusion as well as during pregnancy.

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“…This recognition has opened the possibility of preventing anti-HPA-1a-associated FNAIT by the administration of HPA-1a antibodies to HPA1aYnegative women who have given birth to an HPA1aYpositive childVin principle the same strategy as has been used successfully for the prevention of HDFN. 51 It has recently been demonstrated in a proof-ofprinciple study that administration of polyclonal antiY HPA-1a purified from HPA-1aYimmunized women, as well as a monoclonal antiYHPA-1a (clone SZ21), was able to suppress the antibody response in A3 integrin (GPIIIa)Ydeficient (A3 j/j ) or knockout mice after transfusion of (human) HPA-1aYpositive platelets. 52 This study also employed a mouse model of FNAIT in which the pubs of of A3 j/j mice bred with wildtype BALB/c mice were examined for clinical signs of FNAIT.…”

Section: Toward Prevention Of Fnaitmentioning

confidence: 99%

Mechanisms and Prevention of Alloimmunization in Pregnancy

Kjeldsen‐Kragh¹,

Skogen²

2013

Obstetrical &Amp; Gynecological Survey

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Transfusion only occasionally gives rise to antibody production, because blood cells per se are not markedly immunogenic. However, the immunological changes that occur during pregnancy increase the risk of alloimmunization against red blood cells, platelets, and/or leukocytes. Fetal-maternal bleeding during pregnancy or in relation to delivery is the antigenic stimuli for immunization against red blood cells, whereas other mechanisms, such as trophoblast-derived microparticles, may also play a role in the production of antibodies against platelets. Antibody-mediated immune suppression has for 4 decades successfully been used for prevention of RhD immunization. Result from a mouse model of fetal and neonatal alloimmune thrombocytopenia (FNAIT) suggests that the same principle may be applied for the prevention of FNAIT. A European Union-funded consortium is presently in the process of developing a hyperimmune anti-human platelet antigen 1a (HPA-1a) immunoglobulin G. The idea is to prevent HPA-1a immunization by administering the drug to nonimmunized HPA-1a-negative women after delivery of an HPA-1a-positive child. The anti-HPA-1a will be purified from plasma collected from women who previously have given birth to a child with FNAIT caused by anti-HPA-1a. If the results of the planned phase III trial are favorable, it is possible that a product for prevention of FNAIT will be available within this decade.

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Reconsidering fetal and neonatal alloimmune thrombocytopenia with a focus on screening and prevention

Cited by 35 publications

References 58 publications

Current perspectives on fetal and neonatal alloimmune thrombocytopenia – increasing clinical concerns and new treatment opportunities

Current perspectives on fetal and neonatal alloimmune thrombocytopenia – increasing clinical concerns and new treatment opportunities

Genetics of Transfusion Recipient Alloimmunization: Can Clues from Susceptibility to Autoimmunity Pave the Way?

Mechanisms and Prevention of Alloimmunization in Pregnancy

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Reconsidering fetal and neonatal alloimmune thrombocytopenia with a focus on screening and prevention

Cited by 35 publications

References 58 publications

Current perspectives on fetal and neonatal alloimmune thrombocytopenia &ndash; increasing clinical concerns and new treatment opportunities

Current perspectives on fetal and neonatal alloimmune thrombocytopenia &ndash; increasing clinical concerns and new treatment opportunities

Genetics of Transfusion Recipient Alloimmunization: Can Clues from Susceptibility to Autoimmunity Pave the Way?

Mechanisms and Prevention of Alloimmunization in Pregnancy

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Current perspectives on fetal and neonatal alloimmune thrombocytopenia – increasing clinical concerns and new treatment opportunities

Current perspectives on fetal and neonatal alloimmune thrombocytopenia – increasing clinical concerns and new treatment opportunities