Transfusion of adult platelets triggers inflammatory responses in newborn mice through both P-selectin-dependent and -independent mechanisms.

BACKGROUND

Liberal platelet transfusion practices increase neonatal morbidity and mortality. The mechanisms underlying this harm are unknown but may involve the immune rather than hemostatic functions of platelets, as well as the significant differences between adult (transfused) and neonatal platelets, particularly the higher P-selectin surface expression on activated adult platelets. In this study, we investigated the immune/inflammatory effects of transfusing adult platelets into newborn mice.

STUDY DESIGN AND

METHODS

Washed platelets from wild-type (WT) or P-selectin-/- adult donors or Tyrode's buffer control were transfused into WT and thrombocytopenic c-MPL-/- pups. Blood was collected 2- or 4-h post-transfusion to measure a panel of plasma inflammatory cytokines, neutrophil extracellular trap (NET) formation, and the percentage of circulating platelet-monocyte and platelet-neutrophil aggregates (PMAs and PNAs).

RESULTS

Transfusion of adult WT platelets into post-natal Day 10 (P10) and 5 (P5) WT pups increased plasma concentrations of inflammatory cytokines 2- and 4-h post-transfusion, including interleukin-6 (IL-6) and Keratinocyte-derived chemokine (KC). Transfusion of WT platelets into P10 thrombocytopenic c-MPL-/- pups similarly increased plasma inflammatory cytokines, PMA and PNA percentages, and NET formation. Compared to WT platelets, P-selectin-/- platelets induced similar elevations in plasma cytokines, but NET formation was attenuated and PMA and PNA percentages were comparable to those of sham-transfused pups.

DISCUSSION: In a murine model of neonatal thrombocytopenia, transfusion of adult platelets increased PMA and PNA percentages, plasma inflammatory cytokines, and NET formation through both P-selectin-dependent and -independent mechanisms. These effects may contribute to the negative outcomes seen with liberal neonatal platelet transfusion practices.