Background Quantitative and qualitative differences in the hemostatic systems exist between neonates and adults, including the presence of “fetal” fibrinogen, a qualitatively dysfunctional form of fibrinogen that exists until 1 yr of age. The consequences of “fetal” fibrinogen on clot structure in neonates, particularly in the context of surgery-associated bleeding, have not been well characterized. Here, the authors examine the sequential changes in clotting components and resultant clot structure in a small sample of neonates undergoing cardiac surgery and cardiopulmonary bypass (CPB). Methods Blood samples were collected from neonates (n = 10) before surgery, immediately after CPB, and after the transfusion of cryoprecipitate (i.e., adult fibrinogen component). Clots were formed from patient samples or purified neonatal and adult fibrinogen. Clot structure was analyzed using confocal microscopy. Results Clots formed from plasma obtained after CPB and after transfusion were more porous than baseline clots. Analysis of clots formed from purified neonatal and adult fibrinogen demonstrated that at equivalent fibrinogen concentrations, neonatal clots lack three-dimensional structure, whereas adult clots were denser with significant three-dimensional structure. Clots formed from a combination of purified neonatal and adult fibrinogen were less homogenous than those formed from either purified adult or neonatal fibrinogen. Conclusions The results of this study confirm that significant differences exist in clot structure between neonates and adults and that neonatal and adult fibrinogen may not integrate well. These findings suggest that differential treatment strategies for neonates should be pursued to reduce the demonstrated morbidity of blood product transfusion.

Emphysema is a unique type of chronic obstructive pulmonary disease, and sex may influence susceptibility. After cigarette smoke exposure, murine males and ovariectomized females developed more severe emphysema. Herein, we present divergent bulk and single-cell transcriptomic profiles between male and female murine lungs. Weighted Gene Co-Expression Network Analysis of the bulk lung RNA sequencing identified a Green gene module that correlated with male sex and ovariectomy. The Green gene module was enriched in common monocyte progenitors, classical monocytes, type 1 dendritic cells, and macrophages from 83,698 murine cells exposed to air or cigarette smoke for five months. Sexual dimorphism altered the compositions and transcriptome of the clusters enriched with the Green gene module. This comprehensive transcriptomic analysis advances our understanding of dynamic cellular responses controlled by sexual dimorphism during the development of emphysematous pulmonary tissue remodeling and reveals potential targets for mechanistic studies in the future.