Bleeding of Unknown Cause: a Swiss Case-control Study

Recruiting

• Conditions: Bleeding Disorder
• Interventions: Diagnostic Test: Thrombin generation; Diagnostic Test: Fibrinolysis; Diagnostic Test: Fibrin clot structure; Diagnostic Test: Coated platelets

• Registration Number: NCT05713734
• Lead Sponsor: University Hospital, Geneva

Brief Summary

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.

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 Timeline

• Study First Submitted: 2023-01-27
• Study First Submitted QC: 2023-01-27
• Study First Posted: 2023-02-06
• Study Start: 2023-04-01
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-10
• Last Update Posted: 2024-12-16
• Primary Completion: 2026-04-01
• Study Completion: 2027-04-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 400

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 & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Patients	Thrombin generation	Patients with bleeding of unknown cause
Patients	Fibrin clot structure	Patients with bleeding of unknown cause
Controls	Thrombin generation	Healthy voluntaries without bleeding tendency
Controls	Coated platelets	Healthy voluntaries without bleeding tendency
Patients	Coated platelets	Patients with bleeding of unknown cause
Patients	Fibrinolysis	Patients with bleeding of unknown cause
Controls	Fibrinolysis	Healthy voluntaries without bleeding tendency
Controls	Fibrin clot structure	Healthy voluntaries without bleeding tendency

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (7)

Ospedale Regionale di Bellinzona; 🇨🇭 Bellinzona, Switzerland

Inselspital - Universitätsspital Bern; 🇨🇭 Bern, Switzerland

Centre Hospitalier Universitaire Vaudois; 🇨🇭 Lausanne, Switzerland

Gruppo Ospedaliero Moncucco; 🇨🇭 Lugano, Switzerland

Kantonsspital St.Gallen; 🇨🇭 St Gallen, Switzerland

USZ - Universitätsspital Zürich; 🇨🇭 Zurich, Switzerland

University Hospital; 🇨🇭 Geneva, Switzerland