a Other: other specificities with antibodies with MIF
higher than 1000: B78, B35, B53, B18, B72, B55, B76, B56, B42, B67, B37
and B62.
Discussion
Anti-HLA antibodies are very common in the serum of pregnant women.
Approximately 7%-39% of pregnant women develop anti-HLA antibodies.
With the development of technology, 49.3% of pregnant women with
antibodies can be detected with the more sensitive Luminex
method[6]. In 18-30% of pregnant women with multiple pregnancies,
anti-HLA antibodies can be detected[7]. While anti-HLA antibodies
rarely cause FNAIT or ANN, whether anti-HLA antibodies can be considered
the cause of FNAIT/ANN is still controversial. Several
theories[8-11] have been postulated to address this discrepancy,
such as differential placental absorption, reduced HLA expression on
neonatal cells, or binding of alloantibodies to fetal macrophages
resulting in inhibition of fetal platelet destruction. However, we
report here a very unusual case of a first twin pregnancy produced in
vitro fertilization by oocyte and semen donation; the two oocytes were
from two donors. HLA-incompatible twin pregnancy due to oocyte donation
might have contributed to the high median fluorescence intensity of the
mother’s antibodies, which were homozygous for class I HLA antigens.
Lashley et al.[12] found that HLA compatibility between donors and
recipients could be relevant for the survival of fetal allografts in OD
pregnancy, and they observed a significantly higher degree of HLA
matching between mothers and children in uncomplicated OD pregnancies
than expected, suggesting that HLA compatibility might be beneficial for
the development of successful and uncomplicated OD pregnancies. In our
case, the two oocytes carrying the HLA genotype may be completely
different, which is why infant 1 did not show symptoms of
thrombocytopenia. We hypothesize that the HLA between mother and infant
1 is more compatible than that between infant 2. However, the family
members refused to test for HLA and antibodies in infant 1.
Although anti-HLA antibody-mediated FNAIT/ANN is a diagnosis of
exclusion and difficult to confirm, the correlation in the case is
strong enough. The immunohematological investigation found no anti-HPA
and anti-HNA antibodies in the mother’s serum or in infant 2. However,
we found anti-HLA-A2, anti-HLA-A24 and anti-HLA-68 antibodies in both
the mother’s serum and infant 2. The surfaces of platelets and
neutrophils do have the same HLA. We believe that the anti-HLA
antibodies may be the reason for FNAIT and ANN in infants. IVIG
transfusion is effective in increasing platelet and neutrophil
counts.G-CSF was not given in the NICU. The infant’s inflammatory
indicators were not increased, blood bacterial culture was also
negative, and the possibility of infection was not considered.
Dahl[13] showed that thrombocytopenic neonates born to mothers with
anti-HLA class I antibodies had a significantly lower birth weight than
controls. An increasing level of maternal anti-HLA class I antibodies
was linearly and inversely associated with birth weight and placental
weight among thrombocytopenic neonates. The birth weight of infant 2 was
2060 g, which is a low birth weight infant (LBWI). However, the birth
weight of infant 1 was 3240 g. These results may explain the difference.
Anemia occurred in infant 2 in the NICU. HLA antibody-induced ANN and/or
NAIT are characterized by the absence of anemia, as mature erythrocytes
do not present HLAs. The direct antiglobulin test (DAT) was positive,
and anemia occurred after treatment with piperacillin sodium and
tazobactam sodium for three days. Anti-piperacillin sodium and
tazobactam sodium antibodies were detected, and hemolysis of the infant
was confirmed to be drug-induced hemolytic anemia (DIHA). The direct
antiglobulin test (DAT) is invaluable for classifying the cause of RBC
destruction as immune or nonimmune[14]. Renard D[15] reported
that the incidence of DIHA is approximately only 1 per million/year, but
penicillins and cephalosporins are frequent causes of DIHA based on a
review of case reports from 2010–2016. This review also examined the
probability of DIHA, and several core elements must be taken into
account: chronological sequence, epidemiological data, objective
evidence, and differential diagnosis. Corticosteroids and IVIG are
effective in treating anemia.
CONFLICT OF INTEREST
The authors declare that there is no conflict of interest.
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