# Genomic and Transcriptomic Influences on Heparin-Induced Thrombocytopenia

> **NIH NIH K01** · UNIVERSITY OF ARIZONA · 2020 · $153,805

## Abstract

ABSTRACT
 Despite decades of research into the immunopathology of heparin-induced thrombocytopenia (HIT), an
unpredictable, life-threatening, immune-mediated adverse reaction to heparin treatment, a fundamental
knowledge gap regarding the cause of HIT remains. The inability to predict HIT represents a considerable liability
associated with heparin administration. Because the exact cellular and molecular mechanisms underlying HIT
have yet to be identified, including the impetus for antibody production and critical immune cell roles, there is an
essential need to apply alternative approaches to understand the biological basis for HIT and to identify clinically
implementable biomarkers. The research objective of this proposal is to determine the role of genomic and
transcriptomic variation in HIT pathogenesis. The PI's central hypothesis is that variation in genomic and
transcriptomic pathways impacts HIT pathogenesis and can be used to identify clinically implementable HIT
biomarkers. Based on strong preliminary data that constitute the first genome-wide association study (GWAS)
and N-of-1 pathways studies for HIT, the working hypothesis is that the upregulation of T cell activation
pathways results in PF4/heparin antibody production and that histo-blood group gene ABO O alleles
subsequently result in HIT through platelet activation. We will pursue two Specific Aims (SAs) to test the central
hypothesis: (1) determine the influence of genomic variation on HIT and (2) identify transcriptomic pathways
involved in HIT pathogenesis using an N-of-1 strategy. In SA #1, a GWAS and gene resequencing approach will
be utilized to identify genetic associations with HIT and platelet factor 4 (PF4)/heparin antibody production. In
SA #2, peripheral blood mononuclear cells (PBMCs) will be collected and RNA-Seq will be performed. The N-
of-1 pathways approach will be utilized to determine up- and down-regulated transcriptomic pathways involved
in HIT and in the development of PF4/heparin antibodies. The proposed research has the potential to garner
significant insights into HIT pathogenesis and to provide a framework for the clinical translation of HIT biomarkers
into early diagnostic and preventive strategies. The proposed studies are technically innovative as they leverage
novel strategies for large-scale biological data, including the N-of-1 pathways approach, and because
establishing tools to distinguish patients that are pre-disposed to HIT could potentially shift current clinical
practice paradigms. The PI's career development objective is to acquire expertise in bioinformatics and the
research tools necessary to address his long-term research goal, including experience in big data, genomic and
transcriptomic pathways, and innovative clinical study approaches. The knowledge and skills garnered during
this award will provide foundational training and resources for future work in pharmacogenomics, facilitate
eventual submission of an R01 proposal, and foster th...

## Key facts

- **NIH application ID:** 9899307
- **Project number:** 5K01HL143137-02
- **Recipient organization:** UNIVERSITY OF ARIZONA
- **Principal Investigator:** Jason Hansen Karnes
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $153,805
- **Award type:** 5
- **Project period:** 2019-04-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9899307

## Citation

> US National Institutes of Health, RePORTER application 9899307, Genomic and Transcriptomic Influences on Heparin-Induced Thrombocytopenia (5K01HL143137-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9899307. Licensed CC0.

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