Cold Stored Whole Blood in Cardiothoracic Surgery

Study Overview
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Brief Summary
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In vitro platelet function and post-transfusion platelet recovery of platelets stored in whole blood decline during storage. In this pilot randomized clinical trial we aim to investigate the impact of storage time of whole blood on the effect and safety in treatment of immediate blood loss in patients undergoing complex cardiothoracic surgery. The study is designed as an exploratory superiority study to support feasibility and provide critical guidance for future, more definitive randomized trials. In the study the test group will receive CPD whole blood leukocyte-depleted with a platelet-sparing filter and stored for 15-21 days whereas the control group patients will receive leukocyte-depleted CPD whole blood stored for less than 7 days.

Detailed Description
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A challenge for implementation of Whole Blood programs in civilian health services has been an uncertainty regarding the impact of storage on the clinical effect of the whole blood transfusion, especially when it comes to platelet function which is essential to hemostasis. In vitro platelet function and post-transfusion platelet recovery decline with increasing storage time of the whole blood. In this pilot randomized clinical trial we aim to investigate the impact of storage time of whole blood on the effect and safety in treatment of immediate blood loss in patients undergoing complex cardiothoracic surgery. The study is designed as an exploratory superiority study to support feasibility and provide critical guidance for future, more definitive randomized trials. In the study the test group will receive CPD whole blood leukocyte-depleted with a platelet-sparing filter and stored for 15-21 days whereas the control group patients will receive leukocyte-depleted CPD whole blood stored for less than 7 days. A control group receiving standard care (blood component-based transfusion) may be included.

Official Title
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Cold Stored Whole Blood in Treatment of Bleeding in Patients Undergoing Cardiothoracic Surgery

Conditions
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Bleeding

Intervention / Treatment
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* Other: Whole Blood transfusion


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients undergoing cardiothoracic, cardiac, or aortic surgery Patients with complex surgical procedures and expected cardiopulmonary bypass (CPB) time over 120 minutes Patients capable of providing informed consent to participate in the study Exclusion Criteria: Patients not capable of providing informed consent to participate or who will not provide informed consent Patients with known congenital coagulopathies or hemostatic disorders (von Willebrands Disease, hemophilia etc) Patients with known erythrocyte- or platelet/HLA antibodies Patients with a particular increased surgical risk with expected need of ECMO Patients with preoperative EuroScore II ≥ 30 5. RhD negative patient

Ages Eligible for Study
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Minimum Age: 18 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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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Test group ( Whole Blood stored for 15-21 days) versus Control group(s) (Whole Blood stored for less than 7 days, Whole Blood stored for 8-14 days and/or Standard Blood Component treatment)
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Whole Blood stored for 15-21 days<br>CPD Whole Blood leukoreduced with a platelet-sparing filter and stored cold for 15-21 days | Other: Whole Blood transfusion<br>* In this study the effect of storage time of whole blood will be investigated. Intervention is storage of whole blood.<br>|
| Active Comparator: Whole Blood stored for less than 7 days<br>CPD Whole Blood leukoreduced with a platelet-sparing filter and stored cold for less than 7 days. We aim at using as fresh as possible. | Other: Whole Blood transfusion<br>* In this study the effect of storage time of whole blood will be investigated. Intervention is storage of whole blood.<br>|
| Active Comparator: Whole Blood stored for 8-14 days<br>CPD Whole Blood leukoreduced with a platelet-sparing filter and stored cold for 8-14 days. This group may be added if deemed of interest after interim analysis. | Other: Whole Blood transfusion<br>* In this study the effect of storage time of whole blood will be investigated. Intervention is storage of whole blood.<br>|
| Active Comparator: Standard Blood Component<br>This group may be added for comparison if deemed of interest after interim analysis. | Other: Whole Blood transfusion<br>* In this study the effect of storage time of whole blood will be investigated. Intervention is storage of whole blood.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Blood loss | Comparison of postoperative immediate blood loss (measured by chest drain output and/or bleeding score) in patients receiving fresher or older cold stored whole blood. | 24 hours (8:00 am morning after surgery) | 
| Blood usage | Comparison of amount of whole blood and blood components given | 24 hours (8:00 am morning after surgery) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| INR | Coagulation measured as INR | 24 hours (8:00 am morning after surgery) | 
| APTT | Coagulation measured as APTT | 24 hours (8:00 am morning after surgery) | 
| Thromboelastography | Thromboelastography (TEG6s) | 24 hours (8:00 am morning after surgery) | 
| Platelet aggregometry | Platelet aggregation measured by Multiplate impedance aggregometry (Mulitplate analyzer) | 24 hours (8:00 am morning after surgery) | 
| Platelet count | Platelet count | 24 hours (8:00 am morning after surgery) | 
| Hemoglobin concentration | Hemoglobin concentration | 24 hours (8:00 am morning after surgery) | 
| Erythrocyte count | Erythrocyte count | 24 hours (8:00 am morning after surgery) | 
| Hematocrit | Hematocrit or erytrocyte volume fraction, i.e.the volume percentage (vol%) of red blood cells (RBC) in blood, | 24 hours (8:00 am morning after surgery) | 
| Fibrinogen concentration | Fibrinogen concentration | 24 hours (8:00 am morning after surgery) | 
| Metabolomic profile | Investigation of blood cell metabolism and metabolic profile by use of high resolution mass spectometry | 24 hours (8:00 am morning after surgery) | 
| White blood cell count | White blood cell count | 24 hours (8:00 am morning after surgery) | 
| Bilirubin | Hemolysis measured as Bilirubin | Up to 7 days | 
| Haptoglobin | Hemolysis measured as Haptoglobin | Up to 7 days | 
| Lactate dehydrogenase | Lactate dehydrogenase (LD) | Up to 7 days | 
| Direct antiglobin test | Direct antiglobin test (DAT) | Up to 7 days | 
| Anti-A antibodies | Anti-A antibodies | Up to 7 days | 
| Anti-B antibodies | Anti-B antibodies | Up to 7 days | 
| Hemostatic agents | Use of hemostatic agents (coagulation factor concentrates, fibriongen concentrate) | 24 hours (8:00 am morning after surgery) | 
| Other medications | Use of other medications potentially affecting bleeding (including tranexamacid, calcium etc.) | 24 hours (8:00 am morning after surgery) | 
| Adverse events | Adverse events | 30 days | 
| Length of stay | Length of stay | 30 days | 
| Mortality | Mortality | 30 days |