PB1408 - Pregnancy-induced change in platelet transcription, metabolism, and aggregation: a longitudinal study from pre-pregnancy to postpartum

Tuesday, July 12, 2022

6:30 PM – 7:30 PM

Location: Exhibition

Presentation Format: In-Person

Presenting Author(s)

EM

Emilie Montenont, PhD

Post doctoral fellow
Molecular Medicine Program, University of Utah, Salt Lake City, UT, USA
Salt Lake City, Utah, United States

Co-Author(s)

HC

Heather Campbell

Assistant Professor
University of Utah
Salt Lake City, Utah, United States
Jesse W. Rowley, PhD

Associate Professor
University Of Utah
Salt Lake City, Utah, United States
NT

Neal Tolley

Research Associate
University of Utah
Salt Lake City, Utah, United States
AB

Antoinette Blair

Program manager
University of Utah
Salt Lake City, Utah, United States
CS

Chris Stubben

Bioinformatics Analyst
University of Utah
Salt Lake City, Utah, United States
JC

James Cox

Associate Professor
University of Utah
Salt Lake City, Utah, United States
RS

Rhonda Souvenir

Assistant Professor
University of Iowa
Iowa City, Iowa, United States
DA

Dale Abel

Professor
UCLA
Los Angeles, California, United States
AW

Andrew Weyrich

President
Oklahoma Medical Research Foundation
Oklahoma City, Oklahoma, United States
Matthew T. Rondina, MD

Professor
Molecular Medicine Program, University of Utah, Salt Lake City, UT, USA; Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT, USA; 4George E. Wahlen Department of Veterans Affairs Medical Center, Geriatric Research, Education, and Clinical Center; Department of Pathology, University of Utah School of Medicine, Salt Lake City, UT, USA
Salt Lake City, Utah, United States
RC

Robert A A. Campbell, PhD

Professor
Molecular Medicine Program, University of Utah, Salt Lake City, UT, USA; Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT, USA
Salt Lake City, Utah, United States

Background: Pregnancy is associated with increased risk for venous thromboembolism. Although previous studies have characterized how pregnancy alters the hemostatic and fibrinolytic system, the effect of pregnancy on platelet function remains relatively unknown.

Aims: We examined platelet activation and aggregation, the transcriptome and metabolome longitudinally beginning prior to pregnancy and continuing through the postpartum period.

Methods: We collected blood from 20 healthy women before pregnancy, during each trimester of pregnancy and 2-6 weeks postpartum. At each visit, we isolated leukocyte-depleted platelets for RNA-sequencing and metabolic studies. Platelet activation basally and in response to agonists was measured by flow cytometry. Washed platelet aggregation was also performed.

Results: The platelet transcriptome and metabolome was significantly altered during pregnancy with the most significant changes occurring in the 3rd trimester. Pathway analysis between pre-pregnancy and the 3rd trimester revealed significant changes to mitochondrial pathways, integrin signaling, and estrogen receptor signaling. In addition, we observed significant changes to platelet-specific genes including FCGR2A, ITGA2B, GP6, and genes regulating procoagulant platelet formation (p < 0.05). Basal platelet activation and in response to agonists did not change significantly over the course of pregnancy or postpartum. In contrast, washed platelet aggregation declined in response to ADP (p < 0.006) and collagen (p < 0.0001) over the course of pregnancy with the lowest response postpartum. Thrombin-induced platelet aggregation significantly increased compared to pre-pregnancy levels during the 2nd (p=0.03) and 3rd (p=0.01) trimester, again with marked decline postpartum (p=0.006 compared to 3rd trimester). Decreased platelet aggregation in the 3rd trimester correlated with increased oxidized glutathione levels and with genes involved with glutathione metabolism, which are known to reduce collagen- and ADP-induced aggregation (r=-0.508, p=0.06).

Conclusion(s): Pregnancy is associated with unique changes in platelet transcription and metabolism. Although not associated with traditional markers of platelet activation, these changes were associated with reduced collagen- and ADP-induced aggregation and increased thrombin-induced aggregation.