Epidemiology and management of fetal and neonatal alloimmune thrombocytopenia

Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a disease in pregnancy characterized by maternal alloantibodies directed against the human platelet antigen (HPA). These antibodies can cause intracranial hemorrhage (ICH) or other major bleeding resulting in lifelong handicaps or death. Optimal fetal care can be provided by timely identification of pregnancies at risk. However, this can only be done by routinely antenatal screening. Whether nationwide screening is cost-effective is still being debated. HPA-1a alloantibodies are estimated to be found in 1 in 400 pregnancies resulting in severe burden and fetal ICH in 1 in 10.000 pregnancies. Antenatal treatment is focused on the prevention of fetal ICH and consists of weekly maternal IVIg administration. In high-risk FNAIT treatment should be initiated at 12–18 weeks gestational age using high dosage and in standard-risk FNAIT at 20–28 weeks gestational age using a lower dosage. Postnatal prophylactic platelet transfusions are often given in case of severe thrombocytopenia to prevent bleedings. The optimal threshold and product for postnatal transfusion is not known and international consensus is lacking. In this review practical guidelines for antenatal and postnatal management are offered to clinicians that face the challenge of reducing the risk of bleeding in fetuses and infants affected by FNAIT.     

Strategies to develop a prophylaxis for the prevention of HPA-1a immunization and fetal and neonatal alloimmune thrombocytopenia

Anti-HPA-1a-antibodies are the main cause of fetal and neonatal alloimmune thrombocytopenia (FNAIT) which may result in intracranial hemorrhage (ICH) and death among fetuses and newborns. Advances in understanding the pathogenesis of FNAIT and proof of concept for prophylaxis to prevent immunization suggest that development of hyperimmune anti-HPA-1a IgG aimed at preventing immunization against HPA-1a and FNAIT is feasible. Anti-HPA-1a IgG can be obtained either by isolating immunoglobulin from already-immunized women or by development of monoclonal anti-HPA-1a antibodies.Here we discuss recent advances that may lead to the development of a prenatal and postnatal prophylactic treatment for the prevention of HPA-1a-associated FNAIT and life-threatening FNAIT-induced complications.     

Implication of antibodies against human leukocyte antigen in simultaneous presentation of fetal and neonatal alloimmune thrombocytopenia and neutropenia

Fetal and neonatal alloimmune thrombocytopenia (FNAIT) and neonatal alloimmune neutropenia (NAN) are two rare complications of newborns caused by antibodies against paternal inherited antigens. Human platelet (HPA) and neutrophil antigens (HNA) are the common targets. Human leukocyte antigen (HLA) class I proteins are also expressed on platelets and neutrophils and anti-HLA antibodies have occasionally been implicated in these complications. We report a premature twin infant who presented with severe thrombocytopenia and neutropenia clinically compatible with FNAIT and NAN, from a mother with no identifiable HPA or HNA antibodies, but with very high levels of complement-fixing antibodies against paternal inherited HLA. These antibodies were also detected in the infant. HLA antibodies are commonly present in multiparous women who deliver healthy infants. They can, however, be cytotoxic and cause clinical complications after blood products transfusion (TRALI and becoming refractory to platelets transfusion) and after organ transplantation (allogeneic organ rejection).     

抗HPA-3a抗体所致新生儿同种免疫性血小板减少性紫癜一例并文献复习

目的 探讨抗血小板特异性抗原(HPA)-3a抗体所致新生儿同种免疫性血小板减少性紫癜(NAITP)的诊断和治疗.方法 采用多重PCR及基因测序技术检测1例出血伴血小板减少新生儿及其父母HPA-1~21bw系统基因型,采用流式细胞术(FCM)和血小板抗原单克隆抗体特异性免疫固定检测技术(MAIPA)检测患儿及其母亲血清血小板特异性抗体并进行特异性鉴定.结果 患儿出生后2 h出现全身多发皮下出血点、血尿及咖啡色呕吐物.基因分型显示患儿为HPA-3ab、母亲为HPA-3bb、父亲为HPA-3aa;患儿及母亲血清中均含与患儿父亲血小板反应的特异性抗体,经MAIPA技术鉴定为抗HPA-3a抗体.结论 发现1例抗HPA-3a抗体所致NAITP患者,通过临床特征分析为该病的诊断和治疗提供借鉴与参考.