Recent progress in understanding the pathogenesis of fetal and neonatal alloimmune thrombocytopenia

Abstract

Summary Fetal and neonatal alloimmune thrombocytopenia (FNAIT) occurs in c. 1 in 1000 births and is caused by maternal antibodies against human platelet alloantigens that bind incompatible fetal platelets and promote their clearance from the circulation. Affected infants can experience bleeding, bruising and, in severe cases, intracranial haemorrhage and even death. As maternal screening is not routinely performed, and first pregnancies can be affected, most cases are diagnosed at delivery of a first affected pregnancy. Unlike its erythrocyte counterpart, Haemolytic Disease of the Fetus and Newborn, there is no prophylactic treatment for FNAIT. This report will review recent advances made in understanding the pathogenesis of FNAIT: the platelet alloantigens involved, maternal exposure and sensitization to fetal platelet antigens, properties of platelet Immunoglobulin G antibodies, maternal‐fetal antibody transport mechanisms and efforts to develop an effective FNAIT prophylaxis.

Potential impact of alloimmune antibodies on the neonatal foal

“…; Allen and Stewart ). Despite this intriguing finding, transfer of fetal white cells, RBCs or platelets to maternal circulation during a healthy pregnancy has not been studied in man (Curtis ). Studies investigating the human disease syndrome of haemolytic disease of the fetus and newborn, however, estimate that approximately 0.5–1 mL of fetal blood enters the maternal circulation during an uncomplicated parturition, thus serving as another possible source of foreign alloantigens to the mother (Sebring and Polesky ; Solomonia et al .…”

“…Parallel investigation into fetal cells and DNA in maternal equid blood has not been investigated but is plausible as invasion of fetal antigens is likely in equine pregnancy as the chorionic girdle invades the maternal endometrium to form endometrial cups (Lunn et al 1997;Allen and Stewart 2001). Despite this intriguing finding, transfer of fetal white cells, RBCs or platelets to maternal circulation during a healthy pregnancy has not been studied in man (Curtis 2015). Studies investigating the human disease syndrome of haemolytic disease of the fetus and newborn, however, estimate that approximately 0.5-1 mL of fetal blood enters the maternal circulation during an uncomplicated parturition, thus serving as another possible source of foreign alloantigens to the mother (Sebring and Polesky 1990;Solomonia et al 2012).…”

A man‐made disease: Fetal neonatal alloimmune thrombocytopenia due to incompatibility between oocyte donor and gestational mother

“…Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a potentially life‐threatening bleeding disorder of the fetus or neonate . FNAIT occurs when there is incompatibility between mother and fetus for a human platelet antigen (HPA), and maternal immunoglobulin G (IgG) antibodies are formed against the incompatible HPA, which was inherited from the father . The maternal antibodies cause fetal platelet destruction .…”

“…1 FNAIT occurs when there is incompatibility between mother and fetus for a human platelet antigen (HPA), and maternal immunoglobulin G (IgG) antibodies are formed against the incompatible HPA, which was inherited from the father. 2 The maternal antibodies cause fetal platelet destruction. 3 The incidence of FNAIT is about 1:1,000 live births, and it is the most common cause of severe thrombocytopenia in term healthy neonates.…”

Noninvasive prenatal HPA‐1 typing in HPA‐1a negative pregnancies selected in the Polish PREVFNAIT screening program

“…Maternal anti‐HPA‐1a antibodies may lead to fetal/neonatal alloimmune thrombocytopenia (FNAIT) if the fetus inherits an HPA‐1a antigen that is exposed on the fetal platelets. Anti‐HPA‐1a antibodies are transported through the placenta by neonatal Fc receptor (FcnR) to the fetal blood where they destroy fetal platelets and affect endothelial cells, causing intracranial hemorrhages in the fetus or newborn in 10% to 20% of immunized pregnant women . Anti‐HPA‐1a antibodies can persist in maternal blood for years after delivery and may be a threat to the next HPA‐1a positive fetus.…”