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Prenatal Diagnosis
Published in Victor A. Bernstam, Pocket Guide to GENE LEVEL DIAGNOSTICS in Clinical Practice, 2019
One platelet disorder is neonatal alloimmune thrombocytopenia — a serious bleeding disorder with a risk of intracranial bleeding in utero or during delivery. The alloantigen most frequently responsible for the condition is HPA-la (Zwa or P1A). The alloantigens can be tested on platelets, but when these are not available the amplification of a noncoding DNA sequence directly upstream of the HPA-1a site can be used for analysis.
Case 27
Published in Atul B. Mehta, Keith Gomez, Clinical Haematology, 2017
Maternal serum was found to contain anti-HPA-1A antibodies. The mother's own platelets were HPA-1A negative, and the father and both children were HPA-1A positive (as are more than 95% of people). Thus, a diagnosis of neonatal alloimmune thrombocytopenia was made. The child received transfusion of HPA-1A-negative platelets, which were continued until the child was able to maintain an unsupported count of more than 50 × 109/L. This occurred within 3 weeks as the titre of transplacentally derived antibody fell. High-dose intravenous immunoglobulin may also help to elevate the neonatal platelet count.
Haematological conditions
Published in David M. Luesley, Mark D. Kilby, Obstetrics & Gynaecology, 2016
Blood group antigens are found on the red cell surface. The ABO and Rh groups of antigens are the most clinically significant in clinical transfusion practice. There are numerous other red cell antigens and these can become more significant in multiply transfused patients and during pregnancy. Platelets also have antigens on their cell surface and both red cell and platelet antigens are inherited in a mendelian fashion. Fetal red cells and platelets therefore express both maternal and paternal antigens. As maternal circulation is in contact with fetal cells, maternal antibodies can be formed against the paternally derived antigens, if they are not present on maternal cells. Red cell alloimmunisation can result in fetal or neonatal haemolytic disease. Alloimmunisation against fetal platelet antigens can cause fetal or neonatal alloimmune thrombocytopenia.
Identification and management of fetal anemia due to hemolytic disease
Published in Expert Review of Hematology, 2022
Renske M. van ’t Oever, Carolien Zwiers, Derek de Winter, Masja de Haas, Dick Oepkes, Enrico Lopriore, E.J.(Joanne) Verweij
As mentioned in chapter 2, multiple assays have been developed to estimate disease severity. Those tests can be used for high-risk selection and to guide perinatal management. An interesting current field of research is to explore if determination of the sugar-moiety attached to the Fc-tail of RBC alloantibodies correlates with the pathogenicity of those antibodies. Through binding of the IgG alloantibodies to the fetal RBCs, the Fc-tail can be bound by phagocytes of the reticulo-endothelial system in the spleen. Phagocytes carry different types of Fc receptors, namely FcɣRIa, FcɣRIIa and FcRIIIa. The binding region of the Fc domain has a sugar moiety (glycan) attached to it [91]. The composition of this glycan determines the affinity of the IgG molecule to the IgG Fc receptor type IIIa [22]. In 2014 Kapur et al. found lowered Fc core-fucose in anti-D specific IgG1 to be associated with increased ADCC levels and decreased fetal or neonatal hemoglobin levels [22]. Similar results were found in a different study from this research group when looking at fetal or neonatal alloimmune thrombocytopenia (FNAIT) [92]. These results suggest that the IgG-Fc-glycosylation is important in the destructive capacity of antibodies and could be a potential biomarker for HDFN. These results were supported in a prospective study published in 2017 in which researchers found that altered galactosylation and low fucosylation are associated with developing HDFN [93]. It would be interesting to evaluate the predictive value of IgG-Fc-glycosylation for the occurrence of fetal anemia and the need for IUTs in larger sample size.
Severe thrombocytopenia and intracranial hemorrhage in a newborn with Noonan syndrome and neonatal alloimmune thrombocytopenia
Published in Platelets, 2022
Rebecca Carter, Anna-Kaisa Niemi
Neonatal alloimmune thrombocytopenia has an estimated incidence of 1 in 1200. It is the leading cause of severe thrombocytopenia in newborns and the leading cause of intracranial hemorrhage (ICH) in term infants. Through a mechanism similar to hemolytic disease of the newborn, NAIT results from a maternal antibody directed against a fetal platelet antigen inherited from the father. Maternal alloantibodies cross the placenta and bind fetal platelets, resulting in fetal and neonatal thrombocytopenia. Ten to 20% of affected infants will develop intracranial hemorrhage, the most severe complication of NAIT. As thrombocytopenia is frequently present prior to delivery, an estimated 80% of these intracranial hemorrhages occur prenatally. Spontaneous resolution of thrombocytopenia is typically observed in the first two weeks of life in infants with NAIT, though low platelet counts can rarely persist for months [11].
Congenital thrombocytopenia associated with a heterozygous variant in the MEIS1 gene encoding a transcription factor essential for megakaryopoiesis
Published in Platelets, 2022
Orna Steinberg-Shemer, Naama Orenstein, Tanya Krasnov, Sharon Noy-Lotan, Nathaly Marcoux, Orly Dgany, Joanne Yacobovich, Oded Gilad, Evelyn Shabad, Lina Basel-Salmon, Hannah Tamary
The patient, currently 3 years old, was born in a vaginal delivery at 37 weeks of gestation, weighing 2280 grams. During the last weeks of pregnancy, growth restriction was found; karyotype performed on amniocentesis was normal. Soon after birth, the infant was diagnosed with a diffuse petechial rash and a right vitreous hemorrhage. Her platelet count was 8000/uL with normal mean platelet volume levels. Hemoglobin and white blood cell counts were within the normal range. Brain and abdominal ultrasound studies were normal. Infectious workup including cultures and viral serology was negative, and neonatal alloimmune thrombocytopenia was ruled out. The peripheral blood smear showed a paucity of platelets with no significant morphological abnormalities. Bone marrow cellularity was normal, with a severe paucity of megakaryocytes and a normal morphology of the other lineages (Figure 1). No chromosomal aberrations were detected. At age 4 weeks, she had gastrointestinal bleeding that resolved. In addition, she was diagnosed with an apical ventricular septal defect that did not require any treatment. The mother is of combined Iraqi-Moroccan Jewish origin and the father is of Moroccan-Brazilian-Ashkenazi Jewish origin. No family history of thrombocytopenia or bleeding tendency was noted.