(705) Understanding Proteomics in Cases of Postpartum Hemorrhage

This is a prospective observational study of patients who were at-risk for PPH with study cohorts defined as those who did and did not experience PPH. This data is a subgroup from a single-center within a larger, multicenter industry sponsored study to validate a point-of care viscoelastic assay device, the Quantra® sonorheometry (SEER) system. Samples were analyzed for proteomics by LC-MS/MS following abundant plasma protein depletion, disulfide bond reduction and alkylation, trypsin digestion, TMTpro labelling, and high-pH fractionation. The peptide data was analyzed with Proteome Discoverer 3.0 against the human reviewed protein database from UniProt. Proteins with an abundance in 1/3 or more of the samples were analyzed. Benjamini-Hochberg corrected p-values were reported and a volcano plot created demonstrating fold change.

Results:
A total of 41 patients were included, and of these,  33 (80%) experienced PPH with 121 proteins identified to be either significantly elevated or decreased in cases of PPH when compared to those without PPH (Figure). Myosin light chain kinase (3.84 fold increase, p < 0.001) and creatinine kinase B-type (2.97 fold increase, p< 0.001) were the two most upregulated proteins in cases of PPH. The two most downregulated proteins in cases of PPH were chorionic somatomammotropin hormone 1 (3.90 fold decrease, p< 0.001) and glycoprotein hormone-alpha subunit (1.93 fold decrease, p< 0.001). 

Conclusion:
Upregulated proteins associated with PPH were found to be proteins crucial to the control of PPH as it relates to uterine contractility. Downregulated proteins associated with PPH were found to be hormones with different functional properties in the postpartum state, not commonly thought to relate to uterine contractility. Further research is needed to understand if upregulation and downregulation of the respective proteins are predictive biomarkers for PPH risk.