Heat Shock Protein 47 in Thrombosis

Heat Shock Protein 47: A Novel Biomarker of Thrombosis Risk

The goal of this observational study is to learn if the novel biomarker Heat shock protein 47 (HSP47) can be used as a prognostic marker for vascular disease in people with acute venous thromboembolism (VTE), myocardial infarction (AMI) or ischaemic stroke compared to healthy volunteers. The main questions it aims to answer are:

1. Are platelet levels of HSP47 higher in patients with acute VTE, AMI or stroke, compared to healthy volunteers.
2. Does platelet levels of HSP47 remain elevated in patients with acute thrombotic events compared to healthy volunteers at 3 and 12-months of follow-up.
3. Are platelet levels of HSP47 postively associated with platelet function and negatively associated with fibrinolytic capacity in patients with an acute thrombotic event.

Participants with VTE, AMI or stroke will be giving a blood sample at diagnosis and again after 3 and 12 months of follow-up. Healthy volunteers will be giving a blood sample once.

Study Overview

• Status: Recruiting
• Conditions: Venous Thromboembolism (VTE); Stroke (in Patients With Atrial Fibrillation); Acute Myocardial Infarction With ST Segment Elevation

• Study Type: Observational
• Enrollment (Estimated): 340

Contacts and Locations

• Study Contact: Name: Kathrine A Friis, MD, PhD-fellow; Phone Number: +45 20 65 27 32; Email: katfrs@rm.dk

Study Locations

• Denmark
  • Central Region
    • Aarhus, Central Region, Denmark, 8200
      • Recruiting
      • Aarhus University Hospital
      • Contact: Kathrine A Friis, PhD-student; Phone Number: +45 20 86 75 94; Email: kathrinefriis@live.dk
      • Principal Investigator: Erik L Grove, Assoc. Prof., MD
      • Sub-Investigator: Kathrine A Friis, MD, PhD-fellow
• Germany
  • Berlin, Germany, 12203
    • Recruiting
    • Deutsches Herzzentrum de Charité
    • Contact: Tobias Petzold, Prof., MD; Phone Number: +49 30- 450- 613745; Email: tobias.petzold@dhzc-charite.de
    • Principal Investigator: Tobias Petzold, Prof., MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Participants will be recruited at Aarhus University Hospital at the department of Cardiology (AMI, VTE), Neurology (Stroke) and Radiology (VTE) and at the Blood Bank (Healthy volunteers).

Description

Inclusion Criteria:

• 18 years of age or older
• Informed consent

VTE group:

• Deep vein thrombosis confirmed on ultrasonography OR
• Pulmonary embolism confirmed on computed tomography angiography (CTA)

AMI group:

• ST-segment elevation on electrocardiogram (ECG) AND
• Culprit lesion(s) on coronary angiography

Stroke group:

• Stroke confirmed on magnetic resonance imaging AND
• Atrial fibrillation (Detected on ECG, telemtry or Holter monitoring) AND
• Stroke localisation classic for AFib: cortical, cerebellar, brainstem or subcortical >1.5 cm in diameter

Healthy group:

- Healthy

Exclusion Criteria:

• <18 years of age
• no informed consent
• Known haematological disorders
• Active haematological malignancy
• Severe renal insufficiency defined as eGFR <15 or dialysis

VTE - Pulmonary embolism incidentally detected by CTA conducted for purposes unrelated to pulmonary embolism assessment without concomitant DVT

AMI

• Coronary dissection
• Takotsubo cardiomyopathy

Stroke

- Stroke from other causes, e.g. findings pointing towards large vessel disease

Healthy

• Known acute or chronic disease
• Prior VTE, AMI, stroke or other thromboembolic event

Study Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort
Venous thromboembolism; Patients with acute deep vein thrombosis diagnosed on UL or pulmonary embolism diagnosed on CTA. >18 years of age. 120 patients in total.
Acute myocardial infarction; With ST segment elevation on ECG and confirmed culprit lesion on coronary angiography. >18 years of age. 50 patients in total.
Healthy participants; No known or prior diseases, no medication. >18 years of age. 120 in total.
Stroke; Stroke confirmed on MRI and diagnosis of atrial fibrillation. >18 years of age. 50 patients in total.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Platelet levels of heat shock protein 47 (HSP47) in patients with thrombosis compared to healthy controls	The level of HSP47 on platelets will be measured in a bloodsample. It will be measured using proteomics and flow cytometry.	From enrollment to end of follow-up at 12 months after enrollment. At 3 time points.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in platelet levels of HSP47 over time in patients with thrombosis	The level of HSP47 on platelets will be measured in a bloodsample. It will be measured using proteomics and flow cytometry.	From enrollment to 12 months of follow-up. Measured at 3 time points.
Platelet levels of HSP47 in association to platelet function	The level of HSP47 on platelets will be measured in a bloodsample. It will be measured using proteomics and flow cytometry. Platelet function will be assessed by platelet aggregation and activation using impedance aggregometry and flow cytometry.	From enrollment to 12 months of follow-up. Measured at 3 time points.
Platelet levels of HSP47 in association to fibrinolytic capacity	The level of HSP47 on platelets will be measured in a bloodsample. It will be measured using proteomics and flow cytometry. Fibrinolytic capacity will be assessed by ROTEM (R) tPA methods established in our lab, and by plasma fibrinolysis analyses.	From enrollment to 12 months of follow-up. Measured at 3 time points.

Collaborators and Investigators

• Sponsor: University of Aarhus
• Collaborators: Aarhus University Hospital; Max Planck Institute of Biochemistry; Deutsches Herzzentrum der Charité, Berlin

Publications and helpful links

General Publications

• Thienel M, Muller-Reif JB, Zhang Z, Ehreiser V, Huth J, Shchurovska K, Kilani B, Schweizer L, Geyer PE, Zwiebel M, Novotny J, Lusebrink E, Little G, Orban M, Nicolai L, El Nemr S, Titova A, Spannagl M, Kindberg J, Evans AL, Mach O, Vogel M, Tiedt S, Ormanns S, Kessler B, Dueck A, Friebe A, Jorgensen PG, Majzoub-Altweck M, Blutke A, Polzin A, Stark K, Kaab S, Maier D, Gibbins JM, Limper U, Frobert O, Mann M, Massberg S, Petzold T. Immobility-associated thromboprotection is conserved across mammalian species from bear to human. Science. 2023 Apr 14;380(6641):178-187. doi: 10.1126/science.abo5044. Epub 2023 Apr 13.

Study record dates

Study Major Dates

• Study Start (Actual): December 9, 2024
• Primary Completion (Estimated): August 31, 2027
• Study Completion (Estimated): August 31, 2027

Study Registration Dates

• First Submitted: December 9, 2024
• First Submitted That Met QC Criteria: December 9, 2024
• First Posted (Actual): December 12, 2024

Study Record Updates

• Last Update Posted (Actual): August 21, 2025
• Last Update Submitted That Met QC Criteria: August 15, 2025
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: Biomarker; Stroke; AMI; Novel biomarker; VTE; HSP47; Heat Shock Protein 47; Trombosis
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Heart Diseases; Arrhythmias, Cardiac; Necrosis; Embolism and Thrombosis; Myocardial Ischemia; Ischemia; Thrombosis; Atrial Fibrillation; Thromboembolism; Myocardial Infarction; Infarction; Venous Thromboembolism
• Other Study ID Numbers: HSP47

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No