Fetal and neonatal alloimmune thrombocytopenia: No evidence of systemic inflammation as a modulator of disease severity. Could placental inflammation be key?

Abstract

SummaryIn fetal/neonatal alloimmune thrombocytopenia (FNAIT), maternal alloantibodies against paternal human platelet antigens (HPA) cross the placenta and lead to platelet destruction. The extent of thrombocytopenia varies among neonates, and inflammation may constitute an important trigger. A set of stable inflammatory markers was measured in serum samples from neonates with low platelet counts, of which n = 50 were diagnosed with FNAIT due to anti‐HPA‐1a antibodies and n = 50 were thrombocytopenic without detectable maternal HPA antibodies. Concentrations of C‐reactive protein, soluble CD14, procalcitonin, and sFlt‐1 did not differ between the two cohorts. There was no correlation between C‐reactive protein or soluble CD14 and the platelet count, but a negative correlation between procalcitonin concentrations and the neonatal platelet count in both cohorts. sFlt‐1 concentration and the platelet count were correlated in FNAIT cases exclusively. None of the inflammatory markers was statistically different between cases with and without intracranial haemorrhage. We were unable to identify systemic inflammation as a relevant factor for thrombocytopenia in FNAIT. The antiangiogenic enzyme sFlt‐1, released by the placenta, did correlate with the platelet count in FNAIT cases. Our findings may give rise to the hypothesis that placental inflammation rather than systemic inflammation modulates disease severity in FNAIT.

Does anti‐HPA‐1a affect birthweight in fetal and neonatal alloimmune thrombocytopenia?

“…A recent large study of newborns with FNAIT showed that some babies, especially males again, were small 23 . A separate study in FNAIT concluded, after exploration of levels of procalcitonin, sFlt1, and CD14, that placental rather than systemic inflammation appeared to modulate the severity of FNAIT 24 . One way to synthesize this information is that anti‐HPA‐1a in FNAIT binds to HPA‐1a expressed on syncytiotrophoblasts from the fetal part of the placenta causing villitis, which may in turn result in smaller babies.…”

“…23 A separate study in FNAIT concluded, after exploration of levels of procalcitonin, sFlt1, and CD14, that placental rather than systemic inflammation appeared to modulate the severity of FNAIT. 24 One way to synthesize this information is that anti-HPA-1a in FNAIT binds to HPA-1a expressed on syncytiotrophoblasts from the fetal part of the placenta causing villitis, which may in turn result in smaller babies. Marked placental inflammation has been found in, for exam-ple, preeclampsia to result in smaller babies.…”