Is the Maternal Anti HPA-1a Alloantibody Concentration a Predictive Parameter for Fetal Alloimmune Thrombocytopenia?.
Authors: Kaplan-Gouet Cecile , Martageix Corinne , Jallu Vincent , Bertrand Gerald 
Published: April 2020

Fetal/neonatal alloimmune thrombocytopenia (FNAIT) results from fetomaternal incompatibility for human platelet antigens (HPAs), and the major risk is intracranial hemorrhages (ICH) (up to 20 to 30% of reported cases). In Caucasians HPA-1a is the most frequently involved antigen. The severity of thrombocytopenia usually increases in subsequent pregnancies and antenatal therapy has been developed. Therapy options take into account the risk of ICH in subsequent pregnancies. But until now the only mean to assess the fetal status is performing a fetal blood sampling which carries a risk of fetal loss or premature delivery. The aim of current research is, therefore, to develop non invasive methods for the prediction of disease severity in affected fetuses. We performed a retrospective and prospective study concerning 44 cases of FNAIT, and compared maternal anti HPA-1a alloantibody concentrations with the fetal (FPC) or newborn platelet counts. We recently developed a standardized quantitative MAIPA procedure based on a mathematical approach (four-parameter logistic regression; Bertrand et al., Transfusion, 2005). Taking into account the hemodilution phenomenon during pregnancy maternal anti HPA-1a alloantibody concentrations [expressed in arbitrary units (AU)/mL] were corrected with a factor depending on the gestational term. The results we obtained are as follow: (1) Before antenatal therapy, 31 maternal sera were quantified, when the FPC was concurrently available. Maternal anti HPA-1a alloantibody concentrations &gt;250AU/mL were associated with FPC ≤ 50.109platelets/L in 15/16 cases. Under this threshold 5/15 fetuses were severely affected, showing that the maternal anti HPA-1a alloantibody concentration is predictive of the fetal status only when &gt;250AU/mL. The correlation was statistically validated with Fisher’s exact test only up to 28 weeks of gestation (P=0.015). (2) the maternal anti HPA-1a alloantibody concentration was evaluated for 101 sera during 19 subsequent pregnancies with or without antenatal therapy. We observed a decrease of the maternal anti HPA-1a alloantibody concentration during the pregnancy of 14/19 women including one mother who did not receive any therapy. This decrease was observed despite the correcting factor for the hemodilution. Just before delivery, all women had anti HPA-1a alloantibody concentrations &lt;250AU/mL. In 4 cases there was a therapy failure and severely thrombocytopenic babies required post-natal therapy with IvIgG and/or platelets transfusions.

In conclusion, from our results, the maternal anti HPA-1a alloantibody concentration before 28 weeks of gestation could help to predict the severity of the fetal status, if tested in standardized conditions. During pregnancy a trend of decreasing alloantibody concentration does not allow any conclusion about the effectiveness of therapy. If the results of this study are confirmed by a larger cohort, it could provide obstetricians with clinically useful information, concerning appropriateness and timing of invasive monitoring procedure.