Effects of Sepsis on Neonatal Thrombopoiesis

Abstract

ABSTRACT:We serially evaluated the effects of sepsis and/or necrotizing enterocolitis (NEC) on neonatal thrombopoiesis, using a panel of tests that included platelet counts, thrombopoietin concentrations (Tpo), circulating megakaryocyte progenitor concentrations (CMPs), and reticulated platelets (RPs). Variables analyzed included sepsis type, time after onset of sepsis, platelet counts, and gestational (GA) and postconceptional ages (PCA). Twenty neonates were enrolled. Ten had Gram-negative, six had Gram-positive, and four had presumed sepsis. Four neonates had NEC stage II or higher, and six developed thrombocytopenia. Overall, septic neonates had significantly elevated Tpo concentrations and circulating megakaryocyte progenitors. The highest Tpo levels were associated with Gramnegative or presumed sepsis. RP percentages were increased only in neonates with low platelet counts, while RP counts (RP% ϫ platelet count) were elevated in neonates with high platelet counts. Our findings suggest that septic neonates up-regulate Tpo production, leading to increased megakaryocytopoiesis and platelet release, although the degree of upregulation is moderate. The changes in RP% and RP count most likely reflect increased thrombopoiesis with variable degrees of platelet consumption. In addition, our findings suggest that different factors, likely including level of illness and/or specific platelet or bacterial products, can down-regulate the magnitude of the thrombopoietic response.

Neonatal mice with necrotizing enterocolitis-like injury develop thrombocytopenia despite increased megakaryopoiesis

“…Although we did not investigate the mechanism(s) that may drive platelet production during NEC, low concentrations of lipopolysaccharides are known to stimulate megakaryocyte differentiation and platelet production in conjunction with inflammatory cytokines such as interleukin-6 (35). Our findings are consistent with the observations of Brown et al (10), who showed a modest increase in circulating reticulated platelets and megakaryocytic precursors in human infants with a diagnosis of NEC. However, in a recent study, Cremer et al .…”

“…There is indirect, anecdotal evidence for platelet consumption, seen in the rapid drop in platelet counts in many patients with NEC and in the short-lived rise in platelet concentrations following transfusions (8). However, there is conflicting data from at least two studies that suggest that some premature infants with sepsis or NEC may have suppressed megakaryopoiesis as the sole or contributing cause of thrombocytopenia (9, 10). To understand the mechanism(s) of NEC-related thrombocytopenia, there is a need for robust, developmentally-appropriate preclinical models.…”

Haematological abnormalities in neonatal necrotizing enterocolitis

“…However, it was unclear whether these elevated Tpo levels were the result of increased Tpo production or rather reflected decreased megakaryocytes and therefore sepsis-mediated suppression of megakaryocytopoiesis. To answer this question, Brown et al (17) measured plasma Tpo concentrations, circulating megakaryocyte progenitors, reticulated platelet counts, and the percentage of reticulated platelets in the circulating platelet pool (RP%) in 20 neonates with sepsis and/or NEC. They showed elevated concentrations of Tpo, circulating megakaryocyte progenitors, and RP% in thrombocytopenic neonates, indicating increased Tpo-mediated thrombopoiesis, although the degree of up-regulation was relatively modest.…”

Increasing platelets without transfusion: is it time to introduce novel thrombopoietic agents in neonatal care?

“…31 In the specific cases of ECMO, sepsis, and NEC, the predominant mechanism of the thrombocytopenia is increased platelet activation and consumption, although recent data suggest that neonates with sepsis or NEC can also have an insufficient compensatory increase in thrombopoiesis. 32 Thus, infants with these conditions might be particularly appealing candidates for treatment with Tpo mimetics. However, two important challenges need to be dealt with when considering this approach.…”