A pilot study of the metabolic profiles of apheresis platelets modified by donor age and sex and in vitro short‐term incubation with sex hormones

Abstract

Background Platelets are part of innate immunity and comprise the cellular portion of hemostasis. Platelets express sex hormone receptors on their plasma membrane and sex hormones can alter their function in vitro. Little is known about how age and sex may affect platelet biology; thus, we hypothesized that platelets from males and females have different metabolomic profiles, which may be altered by age and in vitro treatment with sex hormones. Methods Day 1 apheresis platelets were drawn from five 18–53‐year‐old, premenopausal younger females (YF), five ≥54‐year‐old, postmenopausal, older females (OF), five 18–44‐year‐old younger males (YM), and four ≥45‐year‐old older males (OM). Platelets were normalized to a standard concentration and metabolomics analyses were completed. Unsupervised statistical analyses and hierarchical clustering with principal component analyses were completed. Results Platelets from OM had (1) elevated mono‐, di‐ and tri‐carboxylates, (2) increased levels of free fatty acids, acyl‐carnitines, and free amino acids, and (3) increased purine breakdown and deamination products. In vitro incubation with sex hormones only affected platelets from OM donors with trends towards increased ATP and other high‐energy purines and decreases in L‐proline and other amino acids. Conclusion Platelets from OM's versus YF, OF, and YM have a different metabolome implying increased energy metabolism, more free fatty acids, acylcarnitines, and amino acids, and increased breakdown of purines and deamination products. However, only platelets from OM were affected by sex hormones in vitro. Platelets from OM are metabolically distinct, which may impart functional differences when transfused.

Multiomics Signatures of Coagulopathy in a Polytrauma Swine Model Contrasted with Severe Multisystem Injured Patients

“…Among the top metabolic correlates to LY30, we noted energy metabolism-related acetyl-carnitines, which is relevant in light of the role of these metabolites as anticoagulants . Again, fatty acid catabolism in mitochondria is essential to sustain platelet function, a pathway that in platelets is influenced by subject sex and age …”

Omics Signatures of Tissue Injury and Hemorrhagic Shock in Swine

“…First of all, despite the elevated numbers of swine, to ensure the statistical robustness of our findings, only male swine of comparable age and weight were studied. However, it is now emerging a role for sex, age, body mass index, and their combined effects (eg, relevant for sex hormones in premenopausal vs postmenopausal females) in the regulation of coagulation cascades, such as platelet activity or mature platelet counts 45,64–67 . Swine resuscitation was limited to lactated Ringer’s until normalization of MAP, which may have further contributed to dilution effects in the HS groups (isolated, or combined with TI).…”

“…However, it is now emerging a role for sex, age, body mass index, and their combined effects (eg, relevant for sex hormones in premenopausal vs postmenopausal females) in the regulation of coagulation cascades, such as platelet activity or mature platelet counts. 45,[64][65][66][67] Swine resuscitation was limited to lactated Ringer's until normalization of MAP, which may have further contributed to dilution effects in the HS groups (isolated, or combined with TI). Trauma did not include the effects of traumatic brain injury, a leading cause of early mortality in trauma and a contributing factor to coagulopathy of trauma.…”

Omics markers of platelet transfusion in trauma patients

“…Only apheresis PLTs were transfused in this study, so the impact of buffy coat PLTs 46,47 or other products (e.g., pathogen-inactivated PLTs 68 and cold-stored PLTs 48,69 ) remains to be assessed. In this study, we did not have access to samples from the transfused units nor to data on PLT storage duration or donor biology, such as age 29 and sex, 70,71 both factors impacting the omics phenotypes of PLTs at the time of donation as well as their functional activation profiles. Our results not only show feasibility of functional multi-omics studies at the interface of transfusion and critical care medicine but also provide interesting results showing an impact of PLT transfusion on molecular pathways critical to PLT function, coagulation cascades, and inflammation.…”