Search Results (7)

Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a rare condition in which maternal alloantibodies to fetal platelets cause fetal thrombocytopenia that may lead to intracranial hemorrhage (ICH). Off-label intravenous immunoglobulin (IVIg) has for 30 years been the standard of care for pregnant women who previously have had a child with FNAIT. The efficacy of this treatment has never been tested in a placebo-controlled clinical trial. Although IVIg treatment may improve the neonatal outcome in women who previously have had a child with FNAIT-associated ICH, the question is whether IVIg is necessary for all immunized pregnant women at risk of having a child with FNAIT. The results from some recent publications suggest that antenatal IVIg treatment is not necessary for women who are (1) HPA-1a-immunized and HLA-DRB3*01:01-negative, (2) HPA-1a-immunized with a previous child with FNAIT but without ICH or (3) HPA-5b-immunized. If IVIg is not used for these categories of pregnant women, the amount of IVIg used in pregnant women with platelet antibodies would be reduced to less than ¼ of today’s use. This is important because IVIg is a scarce resource, and the collection of plasma for the treatment of one pregnant woman is not only extremely expensive but also requires tremendous donor efforts. Full article

(1) Background: ABO blood group incompatibility between the mother and fetus protects against anti-D immunization by pregnancy. The possible role of ABO incompatibility in protecting against anti-human platelet antigen-1a immunization is unclear. (2) Methods: This study retrospectively screened 817 families (mother-father-neonate trios) of suspected fetal and neonatal alloimmune thrombocytopenia for inclusion. ABO genotypes were determined in 118 mother-child pairs with confirmed alloimmune thrombocytopenia due to anti-HPA-1a antibodies, and 522 mother-child pairs served as the control group. The expression of blood group antigen A on platelets was determined in 199 consecutive newborns by flow cytometry and compared with adult controls. (3) Results: ABO incompatibility between mother and fetus did not protect against anti-human platelet antigen-1a immunization by pregnancy. ABO blood groups of mothers and/or fetuses were not associated with the severity of fetal and neonatal alloimmune thrombocytopenia. The expression pattern of blood group A antigens on the platelets of newborns mirrored that of adults, albeit on a lower level. Blood group A antigen was detected on a subpopulation of neonatal platelets, and some newborns revealed high platelet expression of A determinants on all platelets (type II high-expressers). (4) Conclusion: The lack of a protective effect of ABO incompatibility between mother and fetus against anti-human platelet antigen-1a immunization by pregnancy may indicate that fetal platelets are not the cellular source by which the mother is immunized. Full article

Hemolytic disease of the fetus and newborn (HDFN), as well as fetal and neonatal alloimmune thrombocytopenia (FNAIT), represent two important disease entities that are caused by maternal IgG antibodies directed against nonmaternally inherited antigens on the fetal blood cells. These antibodies are most frequently directed against the RhD antigen on red blood cells (RBCs) or the human platelet antigen 1a (HPA-1a) on platelets. For optimal management of pregnancies where HDFN or FNAIT is suspected, it is essential to determine the RhD or the HPA-1a type of the fetus. Noninvasive fetal RhD typing is also relevant for identifying which RhD-negative pregnant women should receive antenatal RhD prophylaxis. In this review, we will give an overview of the clinical indications and technical challenges related to the noninvasive analysis of fetal RBCs or platelet types. In addition, we will discuss the ethical implications associated with the routine administration of antenatal RhD to all pregnant RhD-negative women and likewise the ethical challenges related to making clinical decisions concerning the mother that have been based on samples collected from the (presumptive) father, which is a common practice when determining the risk of FNAIT. Full article

Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a disease that causes thrombocytopenia and a risk of bleeding in the (unborn) child that result from maternal alloantibodies directed against fetal, paternally inherited, human platelet antigens (HPA). It is hypothesized that these alloantibodies can also bind to the placenta, causing placental damage. This study aims to explore signs of antibody-mediated placental damage in FNAIT. We performed a retrospective study that included pregnant women, their newborns, and placentas. It comprised 23 FNAIT cases, of which nine were newly diagnosed (14 samples) and 14 were antenatally treated with intravenous immune globulins (IVIg) (21 samples), and 20 controls, of which 10 had anti-HLA-class I antibodies. Clinical information was collected from medical records. Placental samples were stained for complement activation markers (C1q, C4d, SC5b-9, and mannose-binding lectin) using immunohistochemistry. Histopathology was examined according to the Amsterdam criteria. A higher degree of C4d deposition was present in the newly diagnosed FNAIT cases (10/14 samples), as compared to the IVIg-treated FNAIT cases (2/21 samples, p = 0.002) and anti-HLA-negative controls (3/20 samples, p = 0.006). A histopathological examination showed delayed maturation in four (44%) placentas in the newly diagnosed FNAIT cases, five (36%) in the IVIg-treated FNAIT cases, and one in the controls (NS). C4d deposition at the syncytiotrophoblast was present in combination with low-grade villitis of unknown etiology in three newly diagnosed FNAIT cases that were born SGA. We conclude that a higher degree of classical pathway-induced complement activation is present in placentas from pregnancies with untreated FNAIT. This may affect placental function and fetal growth. Full article

Background: Incompatibilities between the mother and unborn baby can cause complications that must be identified early to initiate the appropriate treatment. For example, neonatal alloimmune thrombocytopenia (NAIT), neonatal alloimmune neutropenia (NAIN), and morbus hemolyticus neonatorum affect children worldwide. Aim: This literature review aims to depict the similarities and differences between these three disorders from a clinical and mechanistic point of view. Material and Methods: The current literature review entailed conducting a systematic search to locate articles on the three conditions. Different electronic databases, including PsycINFO, PubMed, Web of Science, and CINAHL, were searched using the search terms “neonatal alloimmune thrombocytopenia”, “neonatal alloimmune neutropenia”, “morbus hemolyticus neonatorum”, “NAIT”, “FNAIT”, “fetal”, “NAIN”, and “hemolytic disease of the newborn”. Results: This review shows that these three diseases are caused by incompatibilities between the maternal and fetal immune systems. Furthermore, these conditions can lead to severe complications that hinder fetal development and cause death if not well managed. Discussion: The current literature review shows that NAIT, NAIN, and morbus hemolyticus neonatorum are rare conditions that occur when the mother produces antibodies against the fetal immune system. Thus, there is a need for the early detection of these conditions to initiate appropriate treatment before the child experiences adverse effects. Conclusion: The development of NAIT, NAIN, and morbus hemolyticus neonatorum is linked to the production of antibodies against the fetal immune system and fetal antigens. Further studies are required to determine potential interventions to reduce the risk of developing these three conditions. Full article

Fetal/neonatal allo-immune thrombocytopenia (FNAIT) results from maternal immunization against fetal platelet-specific antigens (HPA) inherited from the father. Most cases involve HPA located on glycoproteins (GP) IbIX, IaIIa and IIbIIIa. Iso-immunizations can also occur in the absence of expression of membrane proteins, such as GPIIb or GPIIIa in Glanzmann patients. CD36 (also called glycoprotein GPIV) deficiency is observed in 3 to 5% of Asian and African populations. We report here the case of a 41-year-old Canadian woman originated from Africa, who delivered a male dead new-born at 39 weeks of gestation. A massive intracranial haemorrhage was identified as being the obvious cause of death. No platelet antibody against GPIbIX, IaIIa, and IIbIIIa was identified by the gold-standard Monoclonal Antibody-specific Immobilization of Platelet Antigens (MAIPA) assay. Surprisingly, anti CD36 iso-antibodies were identified in the maternal serum with a new bead-based multiplex assay. The CD36 gene was sequenced for both parents, and a mutation was identified on Exon 10 of the mother’s CD36 gene, which was absent for the father: NM_000072.3:c.975T>G inducing a STOP codon at position 325 of the mature protein. The absence of CD36 expression on the mother’s platelets was confirmed by flow cytometry. Full article

Neonatal alloimmune thrombocytopenia results from the maternal immune response against fetal-specific antigens inherited from the father. The diagnosis is ascertained only when the maternal alloantibody and the offending antigen present in the newborn are identified. Up until now most laboratories perform DNA extraction for neonatal genotyping from newborn blood samplings. In order to avoid such an invasive procedure, two protocols of DNA extraction from buccal swabs were developed: a manual protocol using the QIAamp mini blood kit (Qiagen), and an automated procedure with the MagNA Pure Compact instrument (Roche). Both EDTA-blood and buccal swabs from thrombocytopenic newborns were genotyped manually (14 samples), automatically (15 samples) or both manually and automatically (two samples). Human Platelet Antigen (HPA) genotyping was performed using the BeadChip assay (BioArray, Immucor). Concordant genotypings were obtained for all samples except for one swab with the manual method. The automated DNA extraction from newborn buccal swabs with the MagNA Pure Compact instrument was chosen as the first-line strategy, with a significant gain of time in processing buccal swabs. Full article