HLA Antibodies and Neonatal Alloimmune Thrombocytopenia

Abstract

A female baby with a severe thrombocytopenia at 18 × 10⁹/l was born to a 29-year-old (gestation 2/partum 2) mother. Scattered petechiae were present on her legs, arms, chest and face, but there was no bleeding, infection, fever or hepatosplenomegaly. A platelet antibody screening immunocapture test was positive, which was performed on the mother’s serum 3, 12 and 38 days after delivery, but no platelet-specific antibodies were found by the monoclonal-antibody-specific immobilization of platelet antigen assay. The baby’s platelets and lymphocytes and the father’s platelets reacted strongly with the HLA antibodies present in the mother’s serum. The neonate was treated with intravenous human immunoglobulin (Tegeline^®, 1 g/kg per day) 1, 2 and 3 days after delivery. The platelet count rose from 18 × 10⁹/l on day 0 to 37 × 10⁹/l on day 3 and to 227 × 10⁹/l on day 12. No platelet transfusion was needed. Several factors which developed hereafter lead us to think that this neonatal alloimmune thrombocytopenia is due to the transplacental passage of maternal HLA antibodies to the baby.

Alloantibodies against MHC Class I: A Novel Mechanism of Neonatal Pancytopenia Linked to Vaccination

“…In humans, MHC class I alloantibodies in individual cases of fetal/neonatal alloimmune thrombocytopenia (FNAIT) have been reported a number of times during the past decades (14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25). In addition to thrombocytopenia, the presence of an associated neutropenia is noticed in a few cases (16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28).…”

Controversy: HLA Antibodies Responsible for Fetal/Neonatal Alloimmune Thrombocytopenia – an Update

“…HLA-C antibodies were associated with rather mild thrombocytopenias (n = 5). Moncharmont et al [3] reported a case of presumed HLA class I antibody-induced FNAITP. The diagnosis was based on the exclusion of infection.…”

“…In summary, the assumed FNAITP-implicating HLA class I alloimmunization are based on inefficiently ruled out HPA antibodies and, in some cases, other reasons of thrombocytopenia in the newborn. Maternal autoimmune disease in association with thrombocytopenia in the newborn was only efficiently ruled out in the papers of Moncharmont et al [3] and Thude et al [4]. HPA-15 was specifically addressed in the publication by Thude et al [4], and is mentioned in the acknowledgment of the report by Moncharmont et al [3].…”

“…Maternal autoimmune disease in association with thrombocytopenia in the newborn was only efficiently ruled out in the papers of Moncharmont et al [3] and Thude et al [4]. HPA-15 was specifically addressed in the publication by Thude et al [4], and is mentioned in the acknowledgment of the report by Moncharmont et al [3]. The reports are merely descriptive without investigations to explain mechanisms where HLA class I antibodies induce FNAITP.…”

“…After carefully discussing the pros and cons, the author concluded that evidence that HLA antibodies may induce FNAITP is rather weak. Since this publication only three new papers have been dealing with neonatal thrombocytopenia which might be due to maternal alloantibodies with HLA class I specificity [2][3][4]. This review focuses on reports and data dealing with an association between an alloimmunization against HLA class I antigens and fetal/neonatal alloimmune thrombocytopenia (FNAITP) that have been published since 2000.…”