Anti‐HPA‐9bw (Max^a) fetomaternal alloimmunization, a clinically severe neonatal thrombocytopenia: difficulties in diagnosis and therapy and report on eight families

Abstract

This analysis confirms that anti-HPA-9bw (Max(a)) FMAIT is not uncommon and was found to be approximately 2 percent of our confirmed FMAIT cases. It is a clinically severe syndrome that requires prompt diagnosis, albeit difficult, and maternal PLT transfusion therapy. Laboratory investigation of a suspected FMAIT case should be carried out in a specialist laboratory well-experienced in optimal testing. Appropriate management and antenatal therapy should be considered for successive pregnancies to prevent fetal bleeding.

Review of neonatal alloimmune thrombocytopenia

“…In Caucasians, ∼80% of cases are due to anti‐HPA‐1a, with lesser contributions by anti‐HPA‐5b (∼15%) and anti‐HPA‐3a (2%) 3,4 . Low‐frequency or ‘private’ antigens (HPA‐6b to ‐14b and HPA‐16b) are also implicated in NAIT; in one series, anti‐HPA‐9bw (with bleeding severity similar to anti‐HPA‐1a) accounted for up to 2% of NAIT cases 5 . There are clinically important differences in HPA gene frequencies in different ethnic groups.…”

Platelets and platelet alloantigens: Lessons from human patients and animal models of fetal and neonatal alloimmune thrombocytopenia

“…These HPAs only account for 2%–5% of all cases of FNAIT, 106,131 however they are typically involved in more severe cases of FNAIT. 142,143 HPA-3b and HPA-9b are in a linkage disequilibrium, explained by the fact that they are located only 19 base pairs apart. 129 HPA-22bw resides on the β-propeller domain, close to the ligand-binding site, which may interfere with fibrinogen and other ligand binding and cause severe bleeding in affected neonates.…”

Heterogeneity of Platelet Alloantigens and Alloantibodies: New Insights into Structure and Function

“…The frequency of all other HPA alloabs is too low to estimate a clear relationship between specificity and clinical consequence. Recent reports suggest that HPA-9w may be more important for FNAIT than previously suspected [16,17]. It will be interesting to study how the clinical presentation of HPA-9w and HPA-3 alloabs compare, since the underlying polymorphisms are located closely to each other.…”