# The interaction of basal risk, pharmacologic ovulation induction, pregnancy and delivery on hemostatic balance

> **NIH NIH R33** · UNIVERSITY OF VERMONT & ST AGRIC COLLEGE · 2020 · $757,955

## Abstract

Pregnancy presents a hematologic paradox. Despite hemorrhage being the leading cause of maternal mortality
worldwide, pregnancy is a well described hypercoaguable state, conferring a significant increase in clinical
thromboembolic events observed during pregnancy and the puerperium. This hypercoagulable state appears
linked to increases in sex hormone levels. However, the vast majority of pregnant women (99.9%) do not have
a thrombotic event during pregnancy or the post-partum period, although bleeding complications and
preeclampsia (with its associated hematologic disorders) exist in approximately 10% of women. Additionally, in
women undergoing pharmacologic ovulation induction the risk of thrombosis in the first trimester is increased up
to 10-fold, but here too the vast majority (99.6%) maintain an appropriate hemostatic balance and remain free of
clinical complications. In this proposal, we will identify compensating mechanisms that confer protection from
thrombosis and build mathematical models that combine these mechanistic insights with an individual's specific
clinical parameters and select biomarker values to predict risk for aberrant hemostasis across pregnancy. R61:
Identify and quantitatively assess the hemostatic pathways in place that may protect against thrombotic events
and how pharmacologic ovulation induction and peripartum events may affect these pathways. We will collect
data to establish a natural history relevant to sex hormone influence during pregnancy. In one cohort, assisted
and natural pregnancy will be longitudinally assessed from pre-pregnancy to the first trimester while in the other
cohort, pregnancy will be followed from the 3rd trimester to several months postpartum comparing cesarean
delivery with and without labor with vaginal delivery. Data will include clinical and anthropometric parameters,
dynamic assessments of hemostatic balance (thrombus stability), biomarker measurements capturing alterations
in pre-pregnancy coagulant/anticoagulant/fibrinolytic components and pathways, and markers of inflammation
and cellular activation. Computational modeling assessing the contributions of the coagulant, anticoagulant and
fibrinolytic proteome of each individual will provide mechanistic insights into observed alterations in hemostatic
balance. R33: 1) Develop models that integrate clinical data, dynamic measures and biomarker data from the
R61 phase to both identify mechanisms that confer protection from thrombosis and to predict individual risk for
the most common clinical problems, including failure to implant during assisted pregnancy and hemorrhage
during delivery; 2) Initiate a longitudinal study of assisted and natural pregnancy in which each individual is
followed from pre-pregnancy into the postpartum period using dynamic and static assays (from R61 phase) that
appeared most responsive to the changes in sex hormone concentrations; 3) Mature and validate the preliminary
models using the longitudinal study data. ...

## Key facts

- **NIH application ID:** 10026344
- **Project number:** 4R33HL141787-03
- **Recipient organization:** UNIVERSITY OF VERMONT & ST AGRIC COLLEGE
- **Principal Investigator:** IRA MARK BERNSTEIN
- **Activity code:** R33 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $757,955
- **Award type:** 4N
- **Project period:** 2018-04-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10026344

## Citation

> US National Institutes of Health, RePORTER application 10026344, The interaction of basal risk, pharmacologic ovulation induction, pregnancy and delivery on hemostatic balance (4R33HL141787-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10026344. Licensed CC0.

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