Bleeding of Unknown Cause: a Swiss Case-control Study (SWISS-BUC)

Bleeding of Unknown Cause, Insight Into a Multifactorial Bleeding Disorder: a Swiss Case-control Study

The goal of this prospective cohort is to identified specific biological patterns in patients with a bleeding of unknown cause and to study the specific mechanisms of the bleeding disorder for each subset of patients.

Study Overview

• Status: Recruiting
• Conditions: Bleeding Disorder
• Intervention / Treatment: Diagnostic test: Thrombin generation; Diagnostic test: Fibrinolysis; Diagnostic test: Fibrin clot structure; Diagnostic test: Coated platelets

Detailed Description

Patients with bleeding of unknown cause are included. At baseline, blood will be drawn to evaluate the hemostatic profile. Findings are compared to a control group of healthy individuals. Patients and controls are followed for 3 years.

• Study Type: Observational
• Enrollment (Estimated): 400

Contacts and Locations

• Study Contact: Name: Alessandro Casini; Phone Number: 0041223729757; Email: alessandro.casini@hcuge.ch

Study Locations

• Switzerland
  • Bellinzona, Switzerland
    • Recruiting
    • Ospedale Regionale di Bellinzona
    • Contact: Eugenia Biguzzi; Phone Number: +4191811886; Email: eugenia.biguzzi@eoc.ch
  • Bern, Switzerland
    • Recruiting
    • Inselspital - Universitätsspital Bern
    • Contact: Ioannis Chanias; Phone Number: +41316640852; Email: ioannis.chanias@insel.ch
  • Geneva, Switzerland
    • Recruiting
    • University Hospital
    • Contact: Alessandro Casini
  • Lausanne, Switzerland
    • Recruiting
    • Centre Hospitalier Universitaire Vaudois
    • Contact: Lorenzo Alberio; Phone Number: +413143432; Email: lorenzo.alberio@chuv.ch
  • Lugano, Switzerland
    • Recruiting
    • Gruppo Ospedaliero Moncucco
    • Contact: Ida Martinelli; Phone Number: +41919608666; Email: Ida.Martinelli@moncucco.ch
  • Sankt Gallen, Switzerland
    • Recruiting
    • Kantonsspital St.Gallen
    • Contact: Lukas Graf; Phone Number: 0041714941111; Email: lukas.graf@zlmsg.ch
  • Zurich, Switzerland
    • Recruiting
    • USZ - Universitätsspital Zürich
    • Contact: Jan-Dirk Studt; Phone Number: +41442553488; Email: jan-dirk.studt@usz.ch

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 65 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Women and men aged 16-65 years who have been diagnosed as patients with bleeding of unknown cause Women and men aged 16-65 years without bleeding tendency

Description

Inclusion Criteria:

• Man with ISTH BAT>3. If the calculated score includes a surgical bleeding, then two other items of the score should be >0
• Woman with ISTH BAT >5 points. If the calculated score includes a surgical or a postpartum bleeding, then two other items of the score should be >0

Exclusion Criteria:

• Ongoing pregnancy
• Intake of antithrombotic treatment or non-steroidal anti-inflammatory drugs for least 10 days at time of blood collection
• Intake of antifibrinolytic or blood product administration (factor concentrate, frozen fresh plasma, prothrombin complex concentrate) for least 14 days before blood collection
• Active cancer (defined as cancer diagnosis within the last five years or treatment within the two last years before study inclusion)
• Active autoimmune disease
• Active chronic inflammatory disease
• Severe liver disease (cirrhosis > Child A)
• Renal insufficiency stage 3
• Active or recent infection (within the last 30 days)
• Recent hospitalization (<3 months)
• Recent surgery (<3 months)
• Recent trauma requiring medical intervention (<3 months)

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Patients; Patients with bleeding of unknown cause	Diagnostic test: Thrombin generation; Measurement of thrombin generation by ST Genesia; Diagnostic test: Fibrinolysis; Measurement of fibrinolysis by Lysis Timer; Diagnostic test: Fibrin clot structure; Measurement of fibrin polymerisation and permeability; Diagnostic test: Coated platelets; Measurement of coated platelets by flow cytometry
Controls; Healthy voluntaries without bleeding tendency	Diagnostic test: Thrombin generation; Measurement of thrombin generation by ST Genesia; Diagnostic test: Fibrinolysis; Measurement of fibrinolysis by Lysis Timer; Diagnostic test: Fibrin clot structure; Measurement of fibrin polymerisation and permeability; Diagnostic test: Coated platelets; Measurement of coated platelets by flow cytometry

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fibrin clot polymerisation	maximal absorption (optical density)	At inclusion
Fibrin clot permeability	darcy coefficient (ks, cm2)	At inclusion
Fibrinolysis	Clot lysis time (min)	At inclusion
Thrombin generation	Endogenous thrombin potential (ETP, nM x min)	At inclusion
Coated platelets	Absolute number of coated platelets	At inclusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fibrinogen gamma' levels	Ratio fibrinogen gamma'/total fibrinogen (%)	At inclusion
Scan electron microscopy	Fibrin fiber diameter (nm)	At inclusion
Clot retraction	Ratio clot weight/serum extruded (%)	At inclusion
Plasmin generation	Plasmin (nM)	At inclusion
Fibrin clot formation (thrombodynamics)	Initial rate of clot growth (μM/min)	At inclusion
Major bleeding episodes	Incidence of major bleeding	Three years
Non-major bleeding episodes	Incidence of clinically relevant non-major bleeding	Three years
Health related quality of life	SF36 questionnaire, 0 - 100 (high score, better outcome)	three years
International Society Thrombosis Hemostasis Bleeding assessment tool	ISTH BAT score, 0 - 56 (high score, worse outcome)	three years

Collaborators and Investigators

• Sponsor: University Hospital, Geneva
• Investigators: Principal Investigator: Alessandro Casini, University Hospitals of Geneva

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2023
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): April 1, 2027

Study Registration Dates

• First Submitted: January 27, 2023
• First Submitted That Met QC Criteria: January 27, 2023
• First Posted (Actual): February 6, 2023

Study Record Updates

• Last Update Posted (Actual): April 29, 2026
• Last Update Submitted That Met QC Criteria: April 28, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Fibrin; Bleeding; Fibrinolysis; Thrombin; Hemostatics
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Hematologic Diseases; Hemorrhagic Disorders; Pathological Conditions, Signs and Symptoms; Hemic and Lymphatic Diseases; Hemorrhage; Hemostatic Disorders; Blood Physiological Phenomena; Circulatory and Respiratory Physiological Phenomena; Hemostasis; Blood Coagulation; Fibrinolysis
• Other Study ID Numbers: CCER 2022-02121

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No