Evaluation of Coagulation Factors and Point-of-care Devices During Veno-venous ECMO Therapy

Study Overview
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Brief Summary
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Hemorrhagic and thromboembolic complications are common in Veno-venous ECMO therapy. The aim of this study is to provide a detailed analysis of the activity of different coagulation factors and changes in functional coagulation measurements as in rotational thrombelastometry and multiple electrode aggregometry in the course of ECMO therapy.

Official Title
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Analysis of the Activity of Different Coagulation Factors and Monitoring of Coagulation Using Point-of-care Devices During a Veno-venous ECMO Therapy

Conditions
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Extracorporeal Membrane Oxygenation Complication, Coagulation Factor Deficiency

Intervention / Treatment
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* Diagnostic Test: Detailed coagulation monitoring


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Need for a Veno-venous extracorporeal membrane oxygenation therapy Exclusion Criteria: Known coagulation disorders Refusal to participate

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Diagnostic Test: Detailed coagulation monitoring|Monitoring of coagulation using activity of coagulation factors, rotational thrombelastometry and multiple electrode aggregometry|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in the activity of coagulation factor II [%] during Veno-venous ECMO therapy | Repeated assessment of the activity of coagulation factor II in % through standard coagulometric methods. | Pre-canulation and 6 hours, 1 day, 3 days, 7 days, 11 days, 15 days and 21 days after canulation | 
| Changes in the activity of coagulation factor V [%] during Veno-venous ECMO | Repeated assessment of the activity of coagulation factor V in % through standard coagulometric methods. | Pre-canulation and 6 hours, 1 day, 3 days, 7 days, 11 days, 15 days and 21 days after canulation | 
| Changes in the activity of coagulation factor VII [%] during Veno-venous ECMO | Repeated assessment of the activity of coagulation factor VII in % through standard coagulometric methods. | Pre-canulation and 6 hours, 1 day, 3 days, 7 days, 11 days, 15 days and 21 days after canulation | 
| Changes in the activity of coagulation factor VIII [%] during Veno-venous ECMO | Repeated assessment of the activity of coagulation factor VIII in % through standard coagulometric methods. | Pre-canulation and 6 hours, 1 day, 3 days, 7 days, 11 days, 15 days and 21 days after canulation | 
| Changes in the activity of coagulation factor IX [%] during Veno-venous ECMO | Repeated assessment of the activity of coagulation factor IX in % through standard coagulometric methods. | Pre-canulation and 6 hours, 1 day, 3 days, 7 days, 11 days, 15 days and 21 days after canulation | 
| Changes in the activity of coagulation factor X [%] during Veno-venous ECMO | Repeated assessment of the activity of coagulation factor X in % through standard coagulometric methods. | Pre-canulation and 6 hours, 1 day, 3 days, 7 days, 11 days, 15 days and 21 days after canulation | 
| Changes in the activity of coagulation factor XII [%] during Veno-venous ECMO | Repeated assessment of the activity of coagulation factor XII in % through standard coagulometric methods. | Pre-canulation and 6 hours, 1 day, 3 days, 7 days, 11 days, 15 days and 21 days after canulation | 
| Changes in the activity of coagulation factor XIII [%] during Veno-venous ECMO | Repeated assessment of the activity of coagulation factor XIII in % through standard coagulometric methods. | Pre-canulation and 6 hours, 1 day, 3 days, 7 days, 11 days, 15 days and 21 days after canulation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| vWF-Antigen | Measurement of the vWF-Antigen | Pre-canulation and 6 hours, 1 day, 3 days, 7 days, 11 days, 15 days and 21 days after canulation | 
| Changes in the vWF:Ristocetin-Cofaktor-Activity in % during Veno-venous ECMO therapy | Repeated assessments of the vWF:Ristocetin-Cofaktor-Activity [%] | Pre-canulation and 6 hours, 1 day, 3 days, 7 days, 11 days, 15 days and 21 days after canulation | 
| Changes in CT-EXTEM | Changes in clotting time (CT) in the extrinsically activated assay (EXTEM) of rotational thrombelastometry (ROTEM), results were noted in seconds. | Pre-canulation, 6 hours, 1 day, 2 days, 4 days, 7 days and 11 days after canulation | 
| Changes in CT-INTEM | Changes in clotting time (CT) in the intrinsically activated assay (INTEM) of rotational thrombelastometry (ROTEM), results were noted in seconds. | Pre-canulation, 6 hours, 1 day, 2 days, 4 days, 7 days and 11 days after canulation | 
| Changes in CT-FIBTEM | Changes in clotting time (CT) in the extrinsically activated assay of rotational thrombelastometry (ROTEM) with the addition of Cytochalasin D to inhibit platelet aggregation (FIBTEM), results were noted in seconds. | Pre-canulation, 6 hours, 1 day, 2 days, 4 days, 7 days and 11 days after canulation | 
| Changes in CT-HEPTEM | Changes in clotting time (CT) in the intrinsically activated assay of rotational thrombelastometry (ROTEM) with the addition of heparin to eliminate heparin effects (HEPTEM), results were noted in seconds. | Pre-canulation, 6 hours, 1 day, 2 days, 4 days, 7 days and 11 days after canulation | 
| Changes in CFT-EXTEM | Changes in clot formation time (CFT) in the extrinsically activated assay (EXTEM) of rotational thrombelastometry (ROTEM), results were noted in seconds. | Pre-canulation, 6 hours, 1 day, 2 days, 4 days, 7 days and 11 days after canulation | 
| Changes in CFT-INTEM | Changes in clot formation time (CFT) in the intrinsically activated assay (INTEM) of rotational thrombelastometry (ROTEM), results were noted in seconds. | Pre-canulation, 6 hours, 1 day, 2 days, 4 days, 7 days and 11 days after canulation | 
| Changes in CFT-FIBTEM | Changes in clot formation time (CFT) in the extrinsically activated assay of rotational thrombelastometry (ROTEM) with the addition of Cytochalasin D to inhibit platelet aggregation (FIBTEM), results were noted in seconds. | Pre-canulation, 6 hours, 1 day, 2 days, 4 days, 7 days and 11 days after canulation | 
| Changes in CFT-HEPTEM | Changes in clot formation time (CFT) in the intrinsically activated assay of rotational thrombelastometry (ROTEM) with the addition of heparin to eliminate heparin effects (HEPTEM), results were noted in seconds. | Pre-canulation, 6 hours, 1 day, 2 days, 4 days, 7 days and 11 days after canulation | 
| Changes in MCF-EXTEM | Changes in maximum clot firmness (MCF) in the extrinsically activated assay (EXTEM) of rotational thrombelastometry (ROTEM), results were noted in millimeters. | Pre-canulation, 6 hours, 1 day, 2 days, 4 days, 7 days and 11 days after canulation | 
| Changes in MCF-INTEM | Changes in maximum clot firmness (MCF) in the intrinsically activated assay (INTEM) of rotational thrombelastometry (ROTEM), results were noted in millimeters. | Pre-canulation, 6 hours, 1 day, 2 days, 4 days, 7 days and 11 days after canulation | 
| Changes in MCF-FIBTEM | Changes in maximum clot firmness (MCF) in the extrinsically activated assay of rotational thrombelastometry (ROTEM) with the addition of Cytochalasin D to inhibit platelet aggregation (FIBTEM), results were noted in millimeters. | Pre-canulation, 6 hours, 1 day, 2 days, 4 days, 7 days and 11 days after canulation | 
| Changes in MCF-HEPTEM | Changes in maximum clot firmness (MCF) in the intrinsically activated assay of rotational thrombelastometry (ROTEM) with the addition of heparin to eliminate heparin effects (HEPTEM), results were noted in millimeters. | Pre-canulation, 6 hours, 1 day, 2 days, 4 days, 7 days and 11 days after canulation | 
| Changes in Alpha angle-EXTEM | Changes in Alpha angle in the extrinsically activated assay (EXTEM) of rotational thrombelastometry (ROTEM), results were noted in degree. | Pre-canulation, 6 hours, 1 day, 2 days, 4 days, 7 days and 11 days after canulation | 
| Changes in Alpha angle-INTEM | Changes in Alpha angle in the intrinsically activated assay (INTEM) of rotational thrombelastometry (ROTEM), results were noted in degree. | Pre-canulation, 6 hours, 1 day, 2 days, 4 days, 7 days and 11 days after canulation | 
| Changes in Alpha angle-FIBTEM | Changes in Alpha angle in the extrinsically activated assay of rotational thrombelastometry (ROTEM) with the addition of Cytochalasin D to inhibit platelet aggregation (FIBTEM), results were noted in degree. | Pre-canulation, 6 hours, 1 day, 2 days, 4 days, 7 days and 11 days after canulation | 
| Changes in Alpha angle-HEPTEM | Changes in Alpha angle in the intrinsically activated assay of rotational thrombelastometry (ROTEM) with the addition of heparin to eliminate heparin effects (HEPTEM), results were noted in degree. | Pre-canulation, 6 hours, 1 day, 2 days, 4 days, 7 days and 11 days after canulation | 
| Changes in arachidonic acid induced platelet aggregation assessed by multiple elcetrode aggregometry (MEA)(ASPItest) | Platelet aggregation after stimulation with arachidonic acid was recorded in aggregational units (AU). | Pre-canulation, 6 hours, 1 day, 2 days, 4 days, 7 days and 11 days after canulation | 
| Changes in adenosine diphosphate (ADP) induced platelet aggregation assessed by multiple elcetrode aggregometry (MEA)(ADPtest) | Platelet aggregation after stimulation with ADP was recorded in aggregational units (AU). | Pre-canulation, 6 hours, 1 day, 2 days, 4 days, 7 days and 11 days after canulation | 
| Changes in thrombin-receptor activating peptide (TRAP) induced platelet aggregation assessed by multiple elcetrode aggregometry (MEA)(TRAPtest) | Platelet aggregation after stimulation with TRAP was recorded in aggregational units (AU). | Pre-canulation, 6 hours, 1 day, 2 days, 4 days, 7 days and 11 days after canulation | 
| Light transmission aggregometry | Measurement of platelet function | 6 hours and 7 days after canulation | 
| Quick | Measurement of Quick in % | Pre-canulation, 6 hours and daily from day 1- day 21after canulation | 
| activated partial thromboplastin time (aPTT) | Measurement of aPTT in seconds | Pre-canulation, 6 hours and daily from day 1- day 21after canulation | 
| Fibrinogen | Measurement of fibrinogen concentration in mg/dl | Pre-canulation, 6 hours and daily from day 1- day 21after canulation | 
| Platelet count | Measurement of platelet count/µl | Pre-canulation, 6 hours and daily from day 1- day 21after canulation | 
| activated clotting time (ACT) | Measurement of ACT in seconds | Pre-canulation, 6 hours and daily from day 1- day 21after canulation | 
| Antithrombin III (ATIII) | Measurement of ATIII in % | Pre-canulation, 6 hours and daily from day 1- day 21after canulation | 
| Measurement of Anti-Xa-Activity in % | Measurement of Anti-Xa-Activity by chromogenic assay to determine heparin effect | Pre-canulation, 6 hours, 1 day, 2 days, 3 days, 4 days, 5, days, 6 days, 7 days, 10, days, 11 days 14 days, 17 days, 19 days and 21 days after canulation | 
| D-Dimers | Measurement of D-Dimers | Pre-canulation, 6 hours, 1 day, 2 days, 3 days, 4 days, 5, days, 6 days, 7 days, 10, days, 11 days 14 days, 17 days, 19 days and 21 days after canulation | 
| hemoglobin | hemoglobin concentration in g/dl | Pre-canulation, 6 hours and daily from day 1- day 21after canulation | 
| leucocyte count | leucocyte count/µl | Pre-canulation, 6 hours and daily from day 1- day 21after canulation | 
| Hemorrhagic complications | Structured documentation of hemorrhagic complications | Daily from day 1-21 | 
| Thrombotic complications | Structured documentation of thrombotic complications | Daily from day 1-21 | 
| Oxygenator State | Structured documentation of the state of the oxygenator including search for thrombotic material | Daily from day 1-21 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ECMO, Coagulation monitoring, point-of-care