In this setting, the decision about prenatal IVIg treatment should be determined by the woman together with her physician

In this setting, the decision about prenatal IVIg treatment should be determined by the woman together with her physician. == 6. pregnant women, the amount of IVIg used in pregnant women with platelet antibodies would be reduced to less than of todays use. This is important because IVIg is a scarce resource, and the collection of plasma for the treatment of one pregnant woman is not only extremely expensive but also requires tremendous donor efforts. Keywords:pregnancy, alloimmunization, intracranial hemorrhage, intravenous immunoglobulin, platelet antibodies == 1. Introduction == Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a rare but potentially severe fetalmaternal condition in which maternal alloantibodies to paternally inherited platelet antigens cause thrombocytopenia in the fetus/newborn. Thus, there is resemblance to the pathogenesis of hemolytic disease of the fetus and newborn (HDFN) where an RhD-negative mother can be RhD-immunized if she gives birth to an RhD-positive child. FNAIT, however, differs from HDFN, as immunization against paternally inherited platelet antigens more often occurs in the first incompatible pregnancy and severe clinical Sch-42495 racemate outcomes are seen even in firstborns [1]. The true Incidence of FNAIT is not known but has been estimated at around 1 in 1500 pregnancies [1]. The clinical spectrum varies from mild thrombocytopenia to severe intracranial hemorrhage (ICH), which has been estimated to occur in around 1 in 10,000 unselected pregnancies [2]. In Caucasians, antibodies to human platelet antigen (HPA)-1a account for approximately 80% of FNAIT cases [1] and HPA-5b antibodies have been considered to be implicated in around 15% of the cases [3]. In some Asian populations, however, the majority of antibodies detected in suspected FNAIT cases are HPA-5b antibodies followed by HPA-4b antibodies [4]. For more than 30 years, it has been known that the propensity to develop antibodies against HPA-1a is closely associated with HLA-DRB3*01:01 [5]. Recently it was shown that the risk of having a neonate with severe FNAIT is extremely low for an HPA-1a-immunized, HLA-DRB3*01:01-negative mother [6]. The HPA-1a/b polymorphism is located on the 3 integrin chain of the IIb3 complex that constitutes the platelets fibrinogen receptor. As the 3 chain forms heterodimers with the V chain of the endothelial cells vitronectin receptor, HPA-1a antibodies also bind to endothelial cells. This may have pathophysiological importance as HPA-1a antibodies that are specific for the V3 complex are suggested to play a key role in women who have given birth to a child with ICH [7]. However, it is not fully understood if or how such subgroups of HPA-1a antibodies relate to ICH risk, and the clinical use of such antibody analyses has not been tested in prospective studies. Whether the quantification of maternal HPA-1a antibody levels could be useful to predict the risk of ICH is also not known. Sch-42495 racemate Therefore, based on current knowledge, the only known ICH risk predictor is an obstetric history with FNAIT. According to early reports, ICH occurs in 1030% of FNAIT cases [8,9,10,11]. Moreover, as the recurrence rate was reported to be very high in subsequent pregnancies and the severity was believed to increase compared to that of the previous affected fetus/infant, similar to in HDFN [8,12], the need for fetal bleeding prophylaxis became obvious. However, due to the rarity of ICH in FNAIT cases, there are many uncertainties regarding the natural history of FNAIT. For this reason, the scientific community has relied heavily on data from retrospective case series collected by fetalmaternal medicine specialists, neonatologists and KSHV K8 alpha antibody reference laboratories spanning two or more decades. This implies fragmentary clinical data, a lack of appropriate control groups and reduced antibody avidity due to repeated thaw and freeze cycles of historic sera. In this review, we will critically examine the scientific foundation for todays management of FNAIT, and we will suggest that the majority of pregnant women at risk of having a child with FNAIT may not necessarily need Sch-42495 racemate the currently applied treatment with intravenous immunoglobulin (IVIg). == 2. Intravenous Immunoglobulin Is the Predominant Treatment for Platelet-Immunized Women == In a landmark paper by Bussel and co-workers from 1988 [13], they reported the results of IVIg treatment (IVIg 1 g/kg/week) in seven pregnant women who previously had had a child with FNAIT. In all children, the platelet count was higher than in their older FNAIT-affected sibling. This paper was subsequently followed by a large number of reports where IVIg, with or without corticosteroids, was used for pregnant women at risk of FNAIT in their newborn. Many of these studies were case reports and case series, while some were randomized clinical trials.