Antenatal management of fetomaternal alloimmune thrombocytopenia—report of 15 affected pregnancies

Abstract

The recognition that spontaneous intracranial haemorrhage (ICH) may occur in utero in fetomaternal alloimmune thrombocytopenia (FMAIT) led us to attempt to prevent this in 15 pregnancies of 11 women who had previously affected infants with FMAIT due to anti-HPA-1a. The antenatal management included fetal platelet transfusions and maternal steroids and/or high-dose intravenous immunoglobulin (IVIgG). In the first pregnancy, ICH occurred between 32 and 35 weeks' gestation before any treatment had been given, emphasizing the need for earlier intervention. Five of the 14 subsequent pregnancies in this study were considered to be severely affected (severe haemorrhagic complications in a previous infant and initial fetal platelet count < 20 x 10(9)/L in this study); four were managed successfully with weekly fetal platelet transfusions started between 18 and 29 weeks and continued until delivery at 33-35 weeks, and one severely affected case who was referred at 36 weeks was managed successfully with a single platelet transfusion prior to delivery. Five pregnancies were considered to be mildly affected (previous infants were unaffected by severe bleeding and initial fetal platelet count > 50 x 10(9)/L in this study). The platelet counts were maintained in one case with steroids and in three with IVIgG without the need for repeated platelet transfusions, but in the fifth the fetal platelet count fell despite steroids and IVIgG and serial platelet transfusions were required. Four pregnancies were unsuccessful; two pregnancies were terminated after severe ICH occurred at an early stage before fetal blood sampling had been carried out, one fetus died after the mother had a severe fall despite the successful initiation of fetal platelet transfusions and one died due to a cord haematoma which occurred at the time of the initial fetal blood sampling. The optimal management of FMAIT to reduce the risk of antenatal ICH remains uncertain. Steroids and IVIgG may be effective in some mildly affected cases but serial fetal platelet transfusions are the preferred therapy for those who are severely affected.

Antenatal management in fetal and neonatal alloimmune thrombocytopenia: a systematic review

“…Of the 26 studies, 17 had a treatment arm with IVIG alone, 19,20,[22][23][24]26,27,[29][30][31][32][33][34][35][36][37][38] 3 studies had a treatment arm with corticosteroids alone, 29,35 and 11 had a study arm that combined IVIG and corticosteroid treatment. 19,20,22,24,32,[35][36][37][39][40][41] There were 2 studies that compared all 3 arms. 35,39 In most studies, IVIG was administered at a dose of 1 g/kg per week.…”

“…35,39 In most studies, IVIG was administered at a dose of 1 g/kg per week. Doses other than 1g/kg per week in $1 case were reported in 9 studies: 0.4 g/kg per day for 5 days, 25,40 19 and as late as 32 weeks' gestation. 18 Two studies administered IVIG directly to the fetus.…”

“…25,27,28,38,42 IUPT in combination with IVIG was used in three studies. 21,33,40 The remainder of IUPTs were performed in addition to a maternal therapy strategy of IVIG and/or steroids. [17][18][19]21,25,28,29,39,42 One study reported FBS and PLT transfusion in all fetuses prior to delivery.…”

“…In 6 fetuses/neonates, the cause of death could not be determined. Ghevaert et al 41 described a fetal loss due to acute amnionitis at 16 weeks' gestation (not related to treatment) and Murphy et al 40 reported a fetal loss after a severe fall of the mother on icy pavement.…”

Developing recombinant HPA-1a–specific antibodies with abrogated Fcγ receptor binding for the treatment of fetomaternal alloimmune thrombocytopenia

“…One in 4 babies born to HPA-1a-immunized mothers have fewer than 20 × 10 9 platelets/l (5-10), which leads to intracranial hemorrhage (ICH) in 10% to 20% of all cases with fetomaternal alloimmune thrombocytopenia (FMAIT), from 16 weeks of pregnancy through the postnatal period (8,11,12). There is no consensus on the most effective antenatal therapy for FMAIT (13).…”