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

Sponsor

University Hospital, Geneva (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05713734

Collaborator

(none)

400

Enrollment

Location

Anticipated Duration (Months)

8.3

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Bleeding Disorder	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 Design

Study Type:

Observational

Anticipated Enrollment :

400 participants

Observational Model:

Case-Control

Time Perspective:

Prospective

Official Title:

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

Anticipated Study Start Date :

Apr 1, 2023

Anticipated Primary Completion Date :

Apr 1, 2026

Anticipated Study Completion Date :

Apr 1, 2027

Arms and Interventions

Arm	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

Arm

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

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

Fibrinogen gamma' levels [At inclusion]
Ratio fibrinogen gamma'/total fibrinogen (%)
Scan electron microscopy [At inclusion]
Fibrin fiber diameter (nm)
Clot retraction [At inclusion]
Ratio clot weight/serum extruded (%)
Plasmin generation [At inclusion]
Plasmin (nM)
Fibrin clot formation (thrombodynamics) [At inclusion]
Initial rate of clot growth (μM/min)
Major bleeding episodes [Three years]
Incidence of major bleeding
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)

Eligibility Criteria

Criteria

Ages Eligible for Study:

16 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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)