# Platelet FcGammaRIIa and Risk of Venous Thromboembolism in Cancer

> **NIH NIH R21** · UNIVERSITY OF VERMONT & ST AGRIC COLLEGE · 2022 · $182,325

## Abstract

Thrombosis is common and contributes significantly to morbidity and mortality in patients with cancer. At least
20% of patients with cancer develop venous thromboembolism (VTE) and another 5% will experience acute
arterial thromboembolism (ATE) due to cancer and its treatment. Current guidelines recommend VTE
thromboprophylaxis in high-risk outpatients. Thromboprophylaxis strategies are inadequate as 50% of high-
risk patients on prophylaxis still develop a VTE, the rate of recurrent VTE is ~24% with a case fatality rate of
14.8%, and the incidence of major bleeding is ~13% with a case fatality rate of 8.9%. We and others have
implicated platelets in both the pathogenesis of VTE as well as cancer growth and metastasis. To investigate a
new biomarker of risk in patients with cancer, we propose a pilot study to determine whether quantification of
platelet FcɣRIIa expression can discriminate risk of VTE and cancer progression. We chose platelet FcɣRIIa
expression because we have found that quantifying platelet surface expression of FcγRIIa identifies patients at
high and low risk of thrombotic arterial events. Thus, we hypothesize that elevated platelet expression of
FcγRIIa will identify patients with cancer who are greater risk of VTE as well as cancer progression. The
proposed studies leverage a clinical research program that was established in 2015 at the University of
Vermont Cancer Center (Venous Thromboembolism Prevention in the Ambulatory Care Clinic [VTEPACC])
and will allow simultaneous access to research samples, thrombosis complications and cancer outcomes in
order to achieve the following specific aims: 1) To determine whether platelet expression of FcγRIIa identifies
cancer patients at high and low risk of VTE, and 2) To determine whether increased platelet expression of
FcγRIIa is associated with a) advanced stage cancer at the time of enrollment and b) greater progression of
cancer. Platelet reactivity is increased in patients with cancer and has been associated with VTE risk. Platelet
expression of FcγRIIa can increase the risk of thrombosis by both increasing platelet reactivity and by
promoting the procoagulant potential of platelets. In addition, platelets promote cancer by facilitating tumor
vascularization, growth, and metastasis. FcγRIIa has been shown to be a key mediator of platelet secretion
and cross-talk between platelets and tumor cells. Thus, we propose that increased platelet FcγRIIa expression
will be linked to enhanced tumor growth and metastasis by facilitating cancer-tumor cell cross-talk and thereby
the activation of platelets that leads to the release of platelet products. Identification of a biomarker capable of
discriminating high and low risk of VTE will provide an important precision tool that could be combined with
existing tools to guide therapy and improve outcomes. Results from aim 2 will provide key preliminary data in
support of novel antiplatelet treatments to limit cancer progression.

## Key facts

- **NIH application ID:** 10351077
- **Project number:** 1R21CA267074-01
- **Recipient organization:** UNIVERSITY OF VERMONT & ST AGRIC COLLEGE
- **Principal Investigator:** Chris Elaine Holmes
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $182,325
- **Award type:** 1
- **Project period:** 2021-12-01 → 2023-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10351077

## Citation

> US National Institutes of Health, RePORTER application 10351077, Platelet FcGammaRIIa and Risk of Venous Thromboembolism in Cancer (1R21CA267074-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10351077. Licensed CC0.

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