Fetal and neonatal alloimmune thrombocytopenia: recommendations for evidence‐based practice, an international approach

Abstract

Fetal and neonatal alloimmune thrombocytopenia (FNAIT) may result in severe bleeding, particularly fetal and neonatal intracranial haemorrhage (ICH). As a result, FNAIT requires prompt identification and treatment; subsequent pregnancies need close surveillance and management. An international panel convened to develop evidence-based recommendations for diagnosis and management of FNAIT. A rigorous approach was used to search, review and develop recommendations from published data for: antenatal management, postnatal management, diagnostic testing and universal screening. To confirm FNAIT, fetal human platelet antigen (HPA) typing, using non-invasive methods if quality-assured, should be performed during pregnancy when the father is unknown, unavailable for testing or heterozygous for the implicated antigen. Women with a previous child with an ICH related to FNAIT should be offered intravenous immunoglobulin (IVIG) infusions during subsequent affected pregnancies as early as 12 weeks gestation. Ideally, HPA-selected platelets should be available at delivery for potentially affected infants and used to increase the neonatal platelet count as needed. If HPA-selected platelets are not immediately available, unselected platelets should be transfused. FNAIT studies that optimize antenatal and postnatal management, develop risk stratification algorithms to guide management and standardize laboratory testing to identify high risk pregnancies are needed.

The use of IVIg in fetal and neonatal alloimmune thrombocytopenia— Principles and mechanisms

“…Nowadays, intravenous immunoglobulin (IVIg) is the first line of treatment. Since its introduction for FNAIT in 1988 by Bussel et al [13], IVIg has been shown to be highly effective in preventing ICH with a 98.7 % success rate [9], however it should be noted that it is used "offlabel" and its effectiveness has therefore never been tested in a placebocontrolled randomized trial [5]. Despite its routine administration, the gestational age at which to start treatment as well as the IVIg dose still vary greatly between centers [2].…”

“…Most commonly an empirical dose of 1 g/kg per week is used in adaptation from the dose used to treat immune thrombocytopenia (ITP) in pregnancy [8]. No conclusive randomized controlled trial has investigated whether the dose of IVIg as well as the treatment start date has an effect on outcome [5]. Mothers are usually stratified into two groups based on the occurrence or non-occurrence of ICH in a previous pregnancy [8].…”

“…A recent guideline recommendation by the International Collaboration for Transfusion Medicine Guidelines (ICTMG) proposes even earlier start dates. Here, treatment is suggested to commence at 12-16 weeks gestation for the high-risk group and at 20-22 weeks gestation for the low-risk group [5].…”

“…This intervention was also initiated by Bussel et al, however the addition of dexamethasone caused significant side effects [13]. Dexamethasone has since been mostly replaced by prednisone at a dose of 0.5 g/kg per day [5] although the benefits remain unclear. A recent systematic review concluded that the majority of studies did not show a significant difference in platelet count, ICH or mortality when comparing standard IVIg treatment to IVIg plus steroids [9].…”

“…The most feared complication is intracranial hemorrhage (ICH) as it carries significant morbidity and mortality and usually occurs during the late stages of pregnancy [1,4]. Up to 20 % of FNAIT neonates [1] are affected by ICH and about 30 % of cases are fatal [5]. Non-fatal cases can be affected by life-long sequela including seizures, intellectual disability or cortical blindness [3,6].…”