Coagulation in Cirrhosis

Study Overview
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Brief Summary
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Out of fear of bleeding, liver cirrhosis patients are often treated prophylactically with blood and coagulation products before minor interventions. The COUCH study will examine whether these patients benefit from a restrictive administration of coagulation products.

Detailed Description
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Patients with cirrhosis commonly have deranged coagulation parameters, in particular thrombocytopenia and/or an increased INR. However, these laboratory findings do not necessarily correlate with an increased tendency of bleeding. In fact, the reduced synthesis of both pro- and anticoagulant factors often equates to a new equilibrium in the coagulation system. Nevertheless, out of fear of bleeding, liver cirrhosis patients with deviated laboratory coagulation parameters are often aggressively treated with coagulation products (such as platelet concentrates and prothrombin complex concentrate (PCC)) before minor interventions and punctures. Since these products can also have procoagulant side effects, we will investigate whether patients with liver cirrhosis without a history of bleeding or clinical bleeding signs benefit from a restrictive substitution regime. The study will be carried out monocentrically at the General Hospital of Vienna, and will include 400 patients divided into two groups (liberal vs. restrictive substitution of thrombocytes and/or PCC) over an est. period of 4 years.

Official Title
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Coagulation in Cirrhosis

Conditions
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Liver Cirrhosis

Intervention / Treatment
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* Drug: Platelet Concentrate
* Drug: Prothrombin Complex Concentrate
* Other: Restricitve Use


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients at the University Hospital of Vienna with diagnosed liver cirrhosis and deranged coagulation parameters (INR >1,5 AND/ OR platelet count <50 G/L) who are scheduled for one of the following elective invasive interventions of the liver Biopsy or puncture Microwave ablation (MWA) or radiofrequency ablation (RFA) Transjugular intrahepatic portosystemic shunt (TIPS) Percutaneous transhepatic cholangiography drain (PTCD) Exclusion Criteria: Missing informed consent or inability to consent Age < 18 years Pregnancy or breastfeeding Manifest ascites Chronic kidney injury stage G4 or G5, KDIGO Uninterrupted anticoagulant therapy, except for acetylsalicylic acid (ASA) History of bleeding or clinical signs of a hemorrhagic diathesis in the physical examination (e.g., petechia, ecchymosis, mucosal bleeding, hemorrhagic diathesis within the family, menorrhagia, prolonged bleeding after surgery)

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
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Liberal substitution of human prothrombin complex and/or platelet concentrates<br>If INR < 1,5: 10 I.E. human prothrombin complex/kg bodyweigt/0,5 INR AND/OR If platelets < 50 G/l: ((50 G/l - measured thrombocyte concentration G/l) x total blood volume) platelet concentrate | Drug: Platelet Concentrate<br>* Liberal use (standard treatment)<br>Drug: Prothrombin Complex Concentrate<br>* Liberal use (standard treatment)<br>* Other names: PPSB;|
| Experimental: Restrictive substitution of human prothrombin complex and/or thrombocytes<br>No substitution of blood products described in the Active Comparator group. | Other: Restricitve Use<br>* Restrictive use of human prothrombin complex and platelet concentrates. No prophylactic substitution.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Major Bleeding | bleeding complication within 3 days after the intervention | 3 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| bleeding complication | bleeding complication within 28 days after the intervention | 28 days | 
| thromboembolic events |  | 28 days | 
| transfusion related complications |  | 28 days | 
| 28 day overall mortality |  | 28 days | 
| 28 day bleeding related mortality |  | 28 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Patient Blood Management, Platelet Concentrates, Transfusion, Coagulation