Fetal and neonatal alloimmune thrombocytopenia in 2022: a response

Abstract

We appreciate the interest by Drs Vander Haar, Berkowitz, and Bussel in our article on antenatal intravenous immunoglobulins (IVIg) in pregnancies at risk of fetal and neonatal alloimmune thrombocytopenia (FNAIT).1Ernstsen S.L. Ahlen M.T. Johansen T. Bertelsen E.L. Kjeldsen-Kragh J. Tiller H. Antenatal intravenous immunoglobulins in pregnancies at risk of fetal and neonatal alloimmune thrombocytopenia: comparison of neonatal outcome in treated and nontreated pregnancies.Am J Obstet Gynecol. 2022; 227: 506.e1-506.e12Abstract Full Text Full Text PDF Scopus (1) Google Scholar Intracranial hemorrhage (ICH) in a fetus or newborn is a serious but infrequent complication in human platelet antigen 1a (HPA-1a)–immunized pregnancies, and our understanding of who will be affected by this complication is limited. Hence, we fully agree with the authors to focus on identifying pregnancies where antenatal IVIg may not be necessary. Although the risk of bleeding is associated with a very low platelet count, this is not sufficient for bleeding to occur. On the contrary, endothelial damage, perhaps caused by antiplatelet antibodies,2Santoso S. Wihadmadyatami H. Bakchoul T. et al.Antiendothelial αvβ3 antibodies are a major cause of intracranial bleeding in fetal/neonatal alloimmune thrombocytopenia.Arterioscler Thromb Vasc Biol. 2016; 36: 1517-1524Crossref PubMed Scopus (63) Google Scholar is a necessary, but not a sufficient, requirement for bleeding. Therefore, the value of fetal and neonatal platelet counts to predict bleeding risk is low. The authors call for fetal and neonatal platelet counts from our cohort, questioning whether the neonates from the non–IVIg-treated pregnancies were at risk of bleeding. However, the non–IVIg-treated subsequent pregnancies had a median platelet count of 21×109/L (Figure). Thus, our cohort showed a phenotype typical for FNAIT. We did not publish these data1Ernstsen S.L. Ahlen M.T. Johansen T. Bertelsen E.L. Kjeldsen-Kragh J. Tiller H. Antenatal intravenous immunoglobulins in pregnancies at risk of fetal and neonatal alloimmune thrombocytopenia: comparison of neonatal outcome in treated and nontreated pregnancies.Am J Obstet Gynecol. 2022; 227: 506.e1-506.e12Abstract Full Text Full Text PDF Scopus (1) Google Scholar because individual platelet counts were unavailable for most of the IVIg-treated controls. We did not imply, as suggested by the authors, that fetuses whose siblings from a previous pregnancy did not have ICH are “immune” to developing ICH in a subsequent pregnancy. Our message was that the risk of ICH among low-risk subsequent pregnancies is low even without antenatal IVIg. Of note, fetal and neonatal ICHs are reported,3Winkelhorst D. Murphy M.F. Greinacher A. et al.Antenatal management in fetal and neonatal alloimmune thrombocytopenia: a systematic review.Blood. 2017; 129: 1538-1547Crossref PubMed Scopus (70) Google Scholar despite antenatal IVIg; therefore, there is no 100% protection with this treatment. Due to lack of randomized placebo-controlled trials on the efficacy of IVIg, our study is the only systematical comparison of results from IVIg-treated and non–IVIg-treated HPA-1a–immunized women, therefore constituting the hitherto best data regarding the efficacy of IVIg. Our results supported the idea of a more restrictive approach of using IVIg in pregnancies at low risk of ICH, as it is essential to balance the use of antenatal IVIg treatment to keep the risk of ICH at a minimum against the risk of overtreatment. To reach this balance, we need to improve our risk prediction tools to identify pregnancies that will benefit from IVIg treatment. Fetal and neonatal alloimmune thrombocytopenia in 2022American Journal of Obstetrics & GynecologyPreviewIn fetal and neonatal alloimmune thrombocytopenia (FNAIT), maternal immunoglobulin G antibodies directed against fetal platelet antigens inherited from the father cross the placenta into the fetal circulation, often resulting in severe thrombocytopenia,1–3 which can cause intracranial hemorrhage (ICH). Randomized studies have demonstrated the effects of intravenous immunoglobulin with or without prednisone to elevate fetal and neonatal platelet counts.4–6 Why some fetuses with very low platelet counts spontaneously develop an ICH in utero and others do not is not understood; however, very low fetal platelet counts are associated with an increased risk of ICH. Full-Text PDF