Bleeding of Unknown Cause: a Swiss Case-control Study

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Bleeding Disorder

Intervention / Treatment
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* Diagnostic Test: Thrombin generation
* Diagnostic Test: Fibrinolysis
* Diagnostic Test: Fibrin clot structure
* Diagnostic Test: Coated platelets


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Patients<br>Patients with bleeding of unknown cause | Diagnostic Test: Thrombin generation<br>* Measurement of thrombin generation by ST Genesia<br>Diagnostic Test: Fibrinolysis<br>* Measurement of fibrinolysis by Lysis Timer<br>Diagnostic Test: Fibrin clot structure<br>* Measurement of fibrin polymerisation and permeability<br>Diagnostic Test: Coated platelets<br>* Measurement of coated platelets by flow cytometry<br>|
| Controls<br>Healthy voluntaries without bleeding tendency | Diagnostic Test: Thrombin generation<br>* Measurement of thrombin generation by ST Genesia<br>Diagnostic Test: Fibrinolysis<br>* Measurement of fibrinolysis by Lysis Timer<br>Diagnostic Test: Fibrin clot structure<br>* Measurement of fibrin polymerisation and permeability<br>Diagnostic Test: Coated platelets<br>* Measurement of coated platelets by flow cytometry<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bleeding, Hemostatics, Fibrin, Fibrinolysis, Thrombin