Thrombelastometry-guided Blood Component Administration Versus Standard of Care in Patients With Decompensated Liver Cirrhosis Undergoing Invasive Procedures (PROTECT-CIRR)

Thrombelastometry-guided Blood Component Administration Versus Standard of Care in Patients With Decompensated Liver Cirrhosis Undergoing High Risk of Bleeding Invasive Procedures

Patients with liver cirrhosis have historically received prophylactic transfusions before invasive procedures with high risk of bleeding. The optimal method for establishing the need of blood transfusion before invasive procedures in cirrhotic patients has not been determined yet, and there are not enough scientific data to warrant empirical transfusion. In many surgical and trauma-related contexts, viscoelastic tests, like Rotational Thromboelastometry (ROTEM), offer a comprehensive assessment of hemostasis, and it has been demonstrated to predict bleeding risk more accurately than traditional coagulation tests. The aim of this project is to evaluate the efficacy of a ROTEM-based algorithm in managing the administration of prophylactic blood components to patients diagnosed with decompensated liver cirrhosis undergoing invasive high risk of bleeding procedures. The investigators hypothesized that ROTEM-based decision-making will lead to a reduction in pre-procedural blood component usage, particularly fresh frozen plasma (FFP), compared with standard of care, whilst maintaining optimal clinical outcomes. The investigators will perform a prospective, single-center, randomized controlled clinical trial in a tertiary university hospital in Romania, comparing ROTEM-guided prophylactic blood component administration to standard of care in patients with decompensated cirrhosis and coagulopathy undergoing invasive procedures. Inclusion criteria: adults (aged 18 years or older) admitted with cirrhosis and an indication for high risk of bleeding invasive procedure defined as: transjugular liver biopsy, transjugular intrahepatic portosystemic shunt, endoscopic retrograde cholangio-pancreatography with sphincterotomy, endoscopic polypectomy of polyps more than 1 cm, variceal banding and complex dental extraction. The primary safety endpoint will be the incidence of major bleeding. Secondary endpoints will be the proportion of blood products transfusion, hospital length of stay, in-hospital and 28-day mortality, incidence of minor bleeding, transfusion related adverse reactions, and cost analysis.

Study Overview

• Status: Recruiting
• Conditions: Liver Cirrhosis With Acute Decompensation
• Intervention / Treatment: Procedure: Blood Products transfusion

Detailed Description

This project will compare two blood transfusion protocols (coagulogram-based and thromboelastometry-based) prior to high risk of bleeding procedures in patients with cirrhosis. The investigators hypothesized that thromboelastometry-guided transfusion protocols are safe and would decrease the need of blood products transfusion compared to an ordinary coagulogram-based protocol in patients with decompensated cirrhosis receiving high risk of bleeding procedures.

• Study Type: Interventional
• Enrollment (Estimated): 116
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Irina Girleanu, Associated Professor; Phone Number: +40762278575; Email: gilda_iri25@yahoo.com

Study Locations

• Romania
  • Iaşi
    • Iași, Iaşi, Romania, 700111
      • Recruiting
      • Institute of Gastroenterology and Hepatology
      • Contact: Cristina Muzica, Lecturer, MD, PhD; Phone Number: +40747521793; Email: lungu.chirstina@yahoo.com
      • Contact: Email: gilda_iri25@yahoo.com
      • Principal Investigator: Irina Girleanu, Associated Professor, MD, PhD
      • Sub-Investigator: Cristina Muzica, Lecturer, MD, Phd
      • Sub-Investigator: Laura Huiban, Lecturer
      • Sub-Investigator: Sebastian Zenovia, Teaching Assistant, MD, PhD
      • Sub-Investigator: Iulian Buzincu, Teaching Assistant, MD, PhD
      • Sub-Investigator: Raluca Avram, Teaching Assistant, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• diagnosed with decompensated liver cirrhosis of any etiology
• planned for a high risk of bleeding invasive procedure
• coagulopathic based on conventional coagulation tests and considered for pre-procedural blood component prophylaxis
• able and willing to provide informed consent

Exclusion Criteria:

• acute liver failure
• current use of anticoagulant treatment
• patients on antiplatelet aggregation agents
• patients who have received FFP, platelet transfusion, cryoprecipitate in the week prior to the procedure
• patients with stage 4 or 5 chronic kidney disease or patients receiving renal replacement therapy
• sepsis

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Standard of care; Takes into account the SCTs -PT/INR, platelet count and serum fibrinogen levels to guide transfusion prior to high risk of bleeding invasive procedure. If INR ≤1.8, platelet count ≥50,000/mm3 and serum fibrinogen ≥120 mg/dL, no transfusion is indicated. Otherwise, if INR >1.8, FFP is transfused at 10 mL per kg of body weight; and/or if platelet count <50,000/mm3, 1 unit per 10 kg of body weight of platelets (up to 10 units) is transfused; and/or if serum fibrinogen <120 mg/dL, 1 unit per 10 kg of body weight of cryoprecipitate is transfused (up to 10 units).	Procedure: Blood Products transfusion; Blood Products transfusion
Experimental: ROTEM-based; The thromboelastometry-based transfusion protocol uses EXTEM and FIBTEM. No transfusion is necessary when CT-EXTEM is ≤80 s and A10-EXTEM is ≥40 mm. For patients in whom CT-EXTEM is >80 s, transfusion of 10 mL per kg of body weight of FFP will be performed. If the patient presents an A10-EXTEM <40 mm, the investigators will further evaluate the A10-FIBTEM. If A10-FIBTEM is ≥10 mm (indicating adequate fibrinogen function), platelet units (1 unit per 10 kg of body weight; maximum 10 units) will be transfused. Otherwise, if A10-FIBTEM is <10 mm (indicating fibrinogen deficiency), cryoprecipitate (1 unit per 10 kg of body weight; maximum 10 units) will be transfused.	Procedure: Blood Products transfusion; Blood Products transfusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The proportion of patients transfused with any blood product	This measure represents the percentage of patients within the study population who received at least one transfusion of any blood component during study period. It is calculated by dividing the number of patients who were administered one or more units of a blood product by the total number of eligible patients in the cohort, and multiplying by 100 to express the result as a percentage. Blood products include platelets, fresh frozen plasma, or cryoprecipitate.	From the enrollment to 30 days after the procedure
The incidence of major bleeding within the first 24 h	The incidence of major bleeding within the first 24 h after high risk of bleeding invasive procedures. It quantifies early clinically significant hemorrhagic complications and is typically expressed as a percentage or rate. For the purposes of this measure, major bleeding is defined according to standardized clinical criteria. Commonly applied definitions include adapted criteria from the International Society on Thrombosis and Haemostasis (ISTH) or similar consensus frameworks. A bleeding event is classified as major if it meets one or more of the following conditions: fatal bleeding, symptomatic bleeding in a critical area or organ (intracranial, intraspinal, intraocular, retroperitoneal, pericardial, or intramuscular with compartment syndrome), a decrease in hemoglobin of ≥2 g/dL (≥20 g/L) within 24 hours attributable to bleeding , transfusion of ≥2 units of packed red blood cells due to acute blood loss, bleeding requiring urgent procedural or surgical intervention.	From the enrollment to 30 days after the procedure

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The incidence of acute transfusion-related adverse events	This measure represents the proportion of transfusion episodes that are complicated by an acute transfusion-related adverse event occurring during or within 24 hours after the administration of a blood component. It will be expressed as a percentage and it will be calculated by dividing the number of transfusion episodes complicated by at least one qualifying acute adverse event by the total number of transfusion episodes administered during the study period. An acute transfusion-related adverse event is defined as a new clinical sign or symptom occurring during transfusion or within 24 hours after completion, for which a causal relationship to the transfused blood component is suspected, probable, or definite. The investigators will evaluate transfusion-associated cardiac overload, acute hemolytic transfusion reactions, anaphylactic reactions, febrile non-hemolytic reactions and urticarial reactions.	From enrollment to 30 days after the procedure
The hospital length of stay	The investigators will evaluate the hospital length of stay in both study arms	From enrollment to 30 days after the procedure
In hospital mortality	This measure represents the proportion of patients who die from any cause during hospital admission. It captures all-cause mortality occurring between the time of hospital admission and discharge and is typically expressed as a percentage of the total eligible patient population.	From the enrollment to discharge or death
30-days mortality	This measure represents the proportion of patients who die from any cause within 30 days of a defined index event. The index event will be high risk of bleeding invasive procedure. The outcome will be expressed as a percentage and will reflect short-term mortality risk beyond the inpatient setting. 30-day mortality is defined as death from any cause occurring within 30 calendar days of the high risk of bleeding invasive procedure regardless of whether the patient is hospitalized, discharged, or transferred at the time of death. Mortality status will be evaluated through telephone follow-up with patients or family members	From date of randomization until the end of the study or the date of death from any cause, whichever came first, assessed up to 30 days.

Collaborators and Investigators

• Sponsor: Grigore T. Popa University of Medicine and Pharmacy
• Investigators: Principal Investigator: Irina Girleanu, Associated Professor, Grigore T. Popa University of Medicine and Pharmacy

Publications and helpful links

General Publications

• Northup, P.G., Garcia-Pagan, J.C., Garcia-Tsao, G., Intagliata, N.M., Superina, R.A., Roberts, L.N., et al. Vascular Liver Dis-orders, Portal Vein Thrombosis, and Procedural Bleeding in Patients With Liver Disease: 2020 Practice Guidance by the American Association for the Study of Liver Diseases. Hepatology 2021, 73, 366-413.
• Riescher-Tuczkiewicz, A., Caldwell, S.H., Kamath, P.S., Villa, E., Rautou, P.E., Nezam, H.A., et al. Expert opinion on bleeding risk from invasive procedures in cirrhosis. JHEP Rep 2024, 6, 100986
• Tangcheewinsirikul, N., Moonla, C., Uaprasert, N., Pittayanon, R., Rojnuckarin, P. Viscoelastometric versus standard coagu-lation tests to guide periprocedural transfusion in adults with cirrhosis: A meta-analysis of randomized controlled trials. Vox Sang 2022, 117, 553-561
• Intagliata, N.M., Davitkov, P., Allen, A.M., Falck-Ytter, Y.T., Stine, J.G. AGA Technical Review on Coagulation in Cirrhosis. Gastroenterology 2021, 161, 1630-1656.
• Villa, E., Bianchini, M., Blasi, A., Denys, A., Giannini, E.G., de Gottardi, A., et al. EASL Clinical Practice Guidelines on prevention and management of bleeding and thrombosis in patients with cirrhosis. J Hepatol 2022, 76, 1151-1184.

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2025
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): October 31, 2026

Study Registration Dates

• First Submitted: February 11, 2026
• First Submitted That Met QC Criteria: February 24, 2026
• First Posted (Actual): February 27, 2026

Study Record Updates

• Last Update Posted (Actual): February 27, 2026
• Last Update Submitted That Met QC Criteria: February 24, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: ROTEM; bleeding risk; blood product transfusion; decompensated liver cirrhosis
• Other Study ID Numbers: 13536 (Stanford IRB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No