Mothers with fetal and neonatal alloimmune thrombocytopenia (FNAIT) do not produce a rare subtype of antibody that targets only one specific blood vessel protein, easing earlier concerns about what drives the most dangerous bleeding complications, according to a study published recently in Blood.
In this study, all anti–HPA-1a antibodies recognized both major β3 integrins, and none were found to bind exclusively to αvβ3, a theory once linked to brain hemorrhages in newborns.
“These findings emphasize the need to reconsider the suggested relationship between endothelial cell–specific antibody properties and disease outcome in FNAIT, and highlight that further research into predictive factors for bleeding and disease severity in FNAIT is required,” stated this study’s authors.
FNAIT occurs when a pregnant person’s immune system creates antibodies against fetal platelets, causing very low platelet counts and a risk of severe bleeding. The most important target is HPA-1a, a feature on the β3 subunit of platelet integrin αIIbβ3, which is also present in a related form on endothelial cells as αvβ3. Earlier work suggested that antibodies aimed only at αvβ3 might damage blood vessels and increase the chance of intracranial hemorrhage.
Read more about causes and risk factors of FNAIT
Researchers examined maternal sera from 29 severe cases of FNAIT and 65 mild cases, along with comparison groups that included pregnancies without HPA-1a antibodies. Severe cases showed far lower platelet counts and included 13 perinatal deaths from intracranial or major internal bleeding.
However, none of the severe or mild cases carried antibodies that recognized only αvβ3. Instead, every sample reacted with both αIIbβ3 on platelets and αvβ3 on endothelial cells.
Using gene-edited cell lines and absorption tests to remove αIIbβ3-binding antibodies, the team showed that once αIIbβ3-reactive antibodies were removed, no meaningful binding to αvβ3 remained. This pattern held even when researchers retested samples previously labeled as αvβ3 specific. The results support the idea that earlier reports likely reflected incomplete antibody absorption rather than a distinct antibody type.
The study also found that anti–HPA-1a antibodies tend to bind more strongly to αIIbβ3 than αvβ3. When integrins were experimentally activated, this difference narrowed and overall antibody binding dropped. These findings suggest that platelet and endothelial integrin shape affects how well antibodies attach.
For patients, the results may help reassure families that the most feared complications in FNAIT are not driven by a hidden, vessel-specific antibody. Instead, overall antibody levels and platelet destruction appear more important for predicting severity. Continued research may guide better screening and treatment strategies in future pregnancies.
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