Predictive value of sequential maternal anti‐HPA‐1a antibody concentrations for the severity of fetal alloimmune thrombocytopenia

Abstract

To cite this article: Bertrand G, Martageix C, Jallu V, Vitry F, Kaplan C. Predictive value of sequential maternal anti-HPA-1a antibody concentrations for the severity of fetal alloimmune thrombocytopenia. J Thromb Haemost 2006; 4: 628-37.Summary. Background: Fetal/neonatal alloimmune thrombocytopenia results from maternal immunization against fetal platelet alloantigens (HPAs), and the major risk is intracranial hemorrhage. The severity of thrombocytopenia increases in subsequent pregnancies, and antenatal therapy has been developed. Until now, the fetal status can only be assessed by fetal blood sampling, which carries a risk of fetal loss or premature delivery. Objectives: To develop non-invasive methods to gain information on the fetal condition. Patients/ methods: Quantification of the maternal anti-HPA-1a alloantibody concentration was performed with a standardized monoclonal antibody-specific immobilization of platelet antigens (MAIPA) procedure for 43 mothers. A correlation between this concentration and the fetal/neonatal platelet counts was studied. Results: (i) Before antenatal therapy, there was a significant correlation between maternal anti-HPA-1a concentrations ‡250 AU mL )1 and fetal thrombocytopenia (2-66 · 10 9 L )1) whatever the gestational age (Fisher's exact test P ¼ 0.0021). (ii) During subsequent pregnancies, we observed a decrease of the maternal anti-HPA-1a concentration for 14/19 women. Just before delivery, all women had anti-HPA-1a concentrations <250 AU mL )1. In four cases, there was a therapy failure and the severely thrombocytopenic babies required postnatal therapy. Conclusion: The maternal anti-HPA-1a concentration could provide obstetricians with clinically useful information concerning the appropriateness and the timing of invasive monitoring procedures. However, though we observed a tendency toward a decrease in maternal antibody concentration after treatment, this finding does not allow us to draw any conclusions on the effectiveness of therapy.

A prospective study of maternal anti-HPA 1a antibody level as a potential predictor of alloimmune thrombocytopenia in the newborn

“…[4][5][6][7][8][9] Results from the present work, including 161 non-compatible pregnancies, further substantiate this relationship. The theoretically best antibody cut-off level for predicting an outcome appraises sensitivity and specificity equally, but is not necessarily the optimal level for use in clinical practice since the consequences of false-negative and false-positive results may be very different.…”

“…27 We and others have previously reported that anti-HPA 1a antibody levels decrease throughout pregnancy in women who have had a previous pregnancy. 9,[28][29][30] The fact that the levels of antibodies to the rubella antigen were stable during pregnancy disproves the hypothesis that the decrease in anti-HPA 1a antibody levels could be due to the normal hemodilution that occurs during pregnancy. Furthermore, women with anti-HPA 1a antibodies and an HPA 1a negative fetus did not experience decreasing anti-HPA 1a levels during pregnancy.…”

“…Immediately after birth, the platelet count was determined in umbilical cord blood and/or from a capillary blood sample from the neonate. We defined severe thrombocytopenia as a platelet count <50×10 9 /L and moderate thrombocytopenia as a platelet count between 50×10 9 /L and 149×10 9 /L. This study was approved by the Regional Committee for Medical Research Ethics, North Norway (approval number: P-REK V 13/1995).…”

“…Several prospective studies have shown a correlation between anti-HPA 1a antibody level and severity of thrombocytopenia in the newborn. [4][5][6][7] A correlation was also found in two retrospective studies, 8,9 whereas one other retrospective study did not find such a relationship. 10 In a recent trial, we documented that identification of women with anti-HPA 1a antibodies, close clinical follow-up during pregnancy, elective Cesarean section and transfusion of compatible platelets to neonates with severe thrombocytopenia, reduce NAIT-related morbidity and mortality.…”

C-reactive protein enhances IgG-mediated phagocyte responses and thrombocytopenia

“…Immunization against HPA-1a occurs in ;1:450 random pregnancies. [8][9][10] Although platelet decrement is related to antibody titer in FNAIT, 8,11,12 this correlation is not strict, as cases with low titers and very low platelet counts, as well as cases with high titers and normal platelet counts, are frequently observed. Recently we found that at least some of this discrepancy is due to differences in the functional quality of these antibodies, determined by its Fc glycosylation, in particular the level of core fucosylation.…”