HPA‐5b (Br^a) neonatal alloimmune thrombocytopenia: clinical and immunological analysis of 39 cases

Abstract

Maternal alloimmunization against fetal platelets can cause fetal and neonatal thrombocytopenia (NAIT). The HPA-1a (PIA1, Zwa) antigen is by far the most common antigen implicated in NAIT. However, today another antigen often linked with that affection is HPA-5b (Br(a)). This is a report of 39 cases of NAIT involving the HPA-5b antigen. Thrombocytopenia may be of grave consequence. Three infants developed intracerebral haemorrhages (ICH). Of these, one died presumably as a consequence of ICH. Central nervous system (CNS) sequelae in the neonatal period was observed in two children. The potential hazards of death or disabling neurologic sequelae following intracerebral haemorrhage call for rapid and reliable diagnosis and effective therapy. Because there is high risk that subsequent pregnancies might be also affected by NAIT, the mothers of a previously affected child should be managed similarly to the HPA-1b mothers (PIA2, Zwb). The antenatal diagnosis of thrombocytopenia should be made and if necessary the in utero therapy instituted.

The human platelet alloantigens Br(a) and Brb are associated with a single amino acid polymorphism on glycoprotein Ia (integrin subunit alpha 2).

“…Anti-Bra is the second most frequent alloantibody involved in neonatal alloimmune thrombocytopenia in the Caucasian population (12,13).…”

Massive fetal hemorrhage and fetomaternal alloimmune thrombocytopenia from human platelet antigen 5b incompatibility: an unusual association

“…In pregnancy, the diagnosis of AIT usually follows the detection of massive fetal hemorrhage leading to severe anemia or death, and is due to HPA-1a in the overwhelming majority of cases 2,6 ; to the best of our knowledge, severe hemorrhage due to HPA-5b alloimmunization has not previously been reported in the fetus.…”

“…In particular, the latter site of hemorrhage is uncommon for AIT, the most common site of cerebral hemorrhage being intraparenchymal 6 . We do not know why the hemorrhage was subdural in this case; it may be speculated that this rare location may be related somehow to the type of antigen involved in the immunization, although reports addressing the types of lesion related to HPA-5b AIT in the neonate confirm the preferential intraparenchymal location 6 .…”

Platelet glycoprotein complex Ia/IIa antibodies cause neonatal alloimmune thrombocytopenia but do not inhibit megakaryopoiesis and platelet recovery after allogeneic cord blood stem cell transplantation

“…14 In contrast, it is known that HPA-5b antibodies may cause severe courses of NAIT with fatal clinical consequences. 15 The maternal HPA-5b antibody led to a distinct thrombocytopenia of the newborn cord blood stem cell donor, indicating that a significant concentration of antibodies has passed the placenta and was bound to target cells.…”