An observational study in Lung Transplantation, Extracorporeal Membrane Oxygenation (ECMO) and Anticoagulants and Bleeding Disorders, sponsored by University Hospital, Motol. Recruiting at 1 site in Czechia. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-06-10.
Sponsored by University Hospital, Motol · Observational
The aim of this observational pilot study is to evaluate the effectiveness and safety of low-molecular-weight heparin (LMWH) compared to unfractionated heparin (UFH) as anticoagulation in perioperative ECMO during bilateral lung transplantation.
The main question this study seeks to answer is:
Does LMWH provide a safe and effective alternative to UFH for ECMO anticoagulation in lung transplantation, with reduced bleeding and thrombotic complications?
Patients undergoing bilateral lung transplantation with perioperative veno-arterial (V-A) ECMO support will be assigned to one of two anticoagulation strategies:
UFH group: Standard UFH anticoagulation monitored using ROTEM. LMWH group: Enoxaparin-based anticoagulation monitored using ROTEM. The study will assess perioperative blood loss, hemoglobin levels, transfusion needs, and thrombotic events. Additional analyses will include coagulation profile assessments using point-of-care (POC) tests, thrombin generation test (TGT), and laboratory coagulation parameters.
Introduction:
Extracorporeal circulation known as "extracorporeal membrane oxygenation" (ECMO) is a method of supportive therapy for terminal respiratory failure (1-3) or temporary replacement of lung function in the perioperative period during lung transplantation (4). In the former case, it is V-V ECMO (veno-venous ECMO), while in the latter case it is V-A ECMO (veno-arterial ECMO). According to the EURO-ELSO recommendations, the use of unfractionated heparin (UFH) is recommended as anticoagulation of the ECMO set (5). However, 40-50% of patients on ECMO experience not only bleeding but also thrombotic complications (6,7). Nowadays, there is an increasing number of case reports and small studies showing that UFH is not used and instead only standard thrombosis prophylaxis with low molecular weight heparin (LMWH) is administered without signs of thrombosis in the ECMO set (8,9). ECMO has been shown to cause impaired primary hemostasis, which can be detected by devices such as the PFA 200, ROTEM-Platelet, and Multiplate. The main pathology involves platelets and to a lesser extent von Willebrand factor (vWF) (10-12). The ECMO system is a high-flow "high shear stress" system that is comparable to the arterial circulation in vivo. In this setting, the so-called "white thrombus" plays a major role in thrombosis formation. Antiplatelet drugs are commonly used to prevent thrombosis in such a system, for example in cardiology and neurology. Thus, it can be assumed that ECMO-induced impairment of primary hemostasis, specifically impaired platelet plug formation, could naturally serve as a prevention of white thrombus formation and thrombosis of the ECMO set. However, prevention of thrombosis in the venous system or on the surface of ECMO cannulae, i.e., prevention of "red thrombus formation", is still necessary because of the existence of the Virchow triad. Since the main target of action of LMWH is factor FXa and the main target of UFH is mainly factor FIIa, it can be assumed that LMWH could be sufficient to prevent thrombosis, with minimal risk of bleeding. It is important to emphasize that LMWH only minimally blocks thrombin generation and affects the conversion of fibrinogen to fibrin only to a limited extent (i.e., thrombin time - TT), unlike UFH. Moreover, ROTEM testing can be used to monitor both UFH and LMWH (13-16). A recent study published by us supports this hypothesis and suggests that the use of LMWH in patients on ECMO support may represent a safe alternative to anticoagulation or thromboprophylaxis. The study shows that its use resulted in a relatively low incidence of bleeding and thrombotic complications (17). Thus, it can be assumed that LMWH will be suitable and effective for the prevention of thrombus formation with minimal risk of bleeding, even in patients undergoing lung transplantation with perioperative ECMO support. This hypothesis is supported by studies that have found that UFH leads to higher platelet activation compared with LMWH (18-20). On the other hand, the use of activated factor FVIIa at low doses of 12 µg/kg appears to be safe (without increasing thrombotic events) and effective in reducing postoperative bleeding in cardiac surgery. Since FVIIa acts at the site of damaged endothelium, it can be assumed that relatively small doses of FVIIa will be sufficient to stop bleeding, but not so high as to cause thrombosis. In addition, it can be assumed that isolated administration of this factor may be less thrombogenic compared with other preparations that also contain factors acting on the axes of the intrinsic clotting pathway, such as prothrombin complex concentrate (PCC, contains FII, FVII, FIX, FX) or Haemate P (contains vWF and FVIII). Therefore, early administration of low-dose FVIIa may represent an effective way to minimize perioperative blood loss without increasing the risk of thrombosis (21). Another property of recombinant activated FVIIa is its ability to positively affect platelet adhesion and aggregation, which is present during ECMO support (20,22).
Aim and nature of the study:
This is a pilot observational study to prospectively compare two groups of patients with different types of anticoagulation (LMWH vs. UFH) undergoing bilateral lung transplantation with perioperative V-A ECMO support.
Hypothesis:
The use of LMWH represents a safe alternative method of ECMO anticoagulation and thromboprophylaxis that reduces the rate of bleeding and thrombotic complications compared to the current method of anticoagulation with UFH.
Methodology:
The study was approved by the Ethics Committee of Motol University Hospital. All patients enrolled in the study will sign an informed consent for participation in the study and data collection. It will be explained to the patients that there are two types of anticoagulation that are currently standardly used at Motol Hospital for patients with ECMO support. The type of anticoagulation will be determined at the discretion of the anaesthesiologist, with the aim of dividing patients as evenly as possible into different groups. Two groups of patients with different types of anticoagulation (LMWH vs. UFH) will be compared. As this is a pilot project, a total of 40 patients will be included in the study, with each group comprising 20 patients.
In case of blood loss ≥ 500 ml and ongoing bleeding, i.e. "wet operating field", the following Motol University bleeding management protocol will be initiated in both UFH and LMWH group:
Note:
Statistical analysis:
statistical program GraphPad will be used, paired t-test, p \< 0.05
361 studies on the registry are indexed under Hemostatic Disorders; 65 are open to participants now.
This study's planned enrollment of 40 is below the median of 120 across 174 observational studies indexed under Hemostatic Disorders.
Browse Hemostatic Disorders studies →University Hospital, Motol is the lead sponsor of 47 studies on the registry; 9 are open to participants now.
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The study population will consist of patients indicated for bilateral lung transplantation from the Czech Republic and Slovakia, who will undergo surgery at Motol Hospital in Prague.
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Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
A score of how well the liver works in people with liver disease such as cirrhosis: class A is mild, B moderate and C severe.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Child-Pugh class
A score of how well the liver works in people with liver disease such as cirrhosis: class A is mild, B moderate and C severe.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Participants in this group will receive unfractionated heparin (UFH) as the standard anticoagulation regimen during perioperative veno-arterial (V-A) ECMO support for bilateral lung transplantation. UFH Administration: A bolus of 20-40 IU/kg UFH will be administered 30 minutes before ECMO initiation. Continuous UFH infusion of 2-6 mL/h (dilution: 100 mg/50 mL) will be maintained. Coagulation Monitoring: ROTEM (EXTEM, INTEM, HEPTEM, FIBTEM) will be used for real-time assessment. The target CT INTEM/CT HEPTEM ratio will be maintained at 1.2-1.5 to guide anticoagulation adjustments. Coagulation and Hemostasis Assessments: Standard laboratory coagulation tests (aPTT, PT, TT, fibrinogen, FXIII, D-dimers, anti-Xa, platelet count, hemoglobin, hematocrit) will be performed at predefined timepoints. Point-of-care (POC) testing and thrombin generation test (TGT) will be used for additional evaluation.
Participants in this group will receive low-molecular-weight heparin (LMWH) as an alternative anticoagulation strategy during perioperative veno-arterial (V-A) ECMO support for bilateral lung transplantation. LMWH Administration: A bolus of 20-40 IU/kg LMWH (Enoxaparin) will be administered 30 minutes before ECMO initiation. Continuous LMWH infusion of 2-6 mL/h (dilution: 100 mg/50 mL) will be maintained. Coagulation Monitoring: ROTEM (EXTEM, INTEM, HEPTEM, FIBTEM) will be used for real-time assessment. The CT INTEM/CT HEPTEM difference will be maintained at 20-30 seconds to guide anticoagulation adjustments. Coagulation and Hemostasis Assessments: Standard laboratory coagulation tests (aPTT, PT, TT, fibrinogen, FXIII, D-dimers, anti-Xa, platelet count, hemoglobin, hematocrit) will be performed at predefined timepoints. Point-of-care (POC) testing and thrombin generation test (TGT) will be used for additional evaluation.
Perioperative Blood Loss
Total volume of blood lost (milliliters, mL) during surgery, measured as the volume collected in suction canisters at the end of the operation, after subtracting irrigation fluids.
Time frame: Measured intraoperatively, at the end of surgery.
Change in Hemoglobin Levels during surgery and within 24 hours after surgery
The difference in hemoglobin levels (g/L) measured at baseline (preoperative) and at the end of surgery and between immediate postoperative levels and after 24 hours after surgery. This outcome evaluates the extent of perioperative blood loss and its impact on oxygen-carrying capacity.
Time frame: Intraoperative: Change in hemoglobin from preoperative levels to the end of surgery. Postoperative: Change in hemoglobin from preoperative levels to 24 hours post-surgery.
Blood Transfusion Requirements during surgery and Within 24 Hours after surgery
The total number of packed red blood cell (PRBC) units transfused to the patient intraoperatively and within the first 24 hours postoperatively. This outcome assesses the extent of blood loss and the need for transfusion support in ECMO-supported lung transplantation.
Time frame: Intraoperative: PRBC transfusions administered during surgery. Postoperative: PRBC transfusions administered within the first 24 hours after surgery.
Incidence of Thrombotic Complications during surhery and within 24 Hours postoperatively.
The number of thrombotic events occurring intraoperatively and within the first 24 hours postoperatively, including ECMO circuit thrombosis, deep vein thrombosis (DVT), arterial thrombosis, pulmonary embolism (PE), myocardial infarction (MI), and ischemic stroke (CVA). Thrombotic complications will be identified based on clinical signs, imaging studies, and laboratory results, including: ECMO circuit thrombosis requiring urgent ECMO replacement. Limb ischemia due to arterial or venous thrombosis. Deep vein thrombosis (DVT) with \>50% luminal obstruction, confirmed by ultrasound. Pulmonary embolism (PE) confirmed by CT pulmonary angiography. Myocardial infarction (MI) diagnosed based on electrocardiographic changes and cardiac biomarkers. Ischemic stroke (CVA) confirmed by neurological examination and brain imaging (CT/MRI).
Time frame: Intraoperative: Thrombotic events occurring during surgery. Postoperative: Thrombotic events occurring within 24 hours after surgery.
Coagulation Profile Assessed by Point-of-Care (POC) Tests
Assessment of coagulation function using point-of-care (POC) testing, including ROTEM Sigma and PFA-200, to evaluate differences in hemostatic profiles between LMWH and UFH anticoagulation strategies during perioperative ECMO support in lung transplantation. ROTEM Sigma: EXTEM, INTEM, FIBTEM, HEPTEM-parameters CT (seconds), CFT (seconds), MCF (mm), ML (%) PFA-200: Col/EPI test for platelet function assessment of CT in seconds
Time frame: Before anticoagulation administration; 5 minutes after anticoagulation; at ≥500 mL blood loss with ongoing bleeding "wet surgical field"; 5 minutes after NovoSeven (activated FVIIa); at end of surgery before ECMO explantation; upon ICU admission
Coagulation Profile Assessed by Thrombin Generation Test (TGT)
Evaluation of coagulation potential and thrombin generation capacity using the Thrombin Generation Test (TGT) to compare the effects of LMWH vs. UFH on hemostatic function in ECMO-supported lung transplantation. Key parameters measured: Lag time (initiation of thrombin formation) in minutes. Peak thrombin concentration (maximum thrombin level) in nanomolar. Time to peak (speed of thrombin generation) in minutes. Endogenous thrombin potential (ETP) (total thrombin formed) in nanomolar minutes.
Time frame: Before anticoagulation administration; 5 minutes after anticoagulation; at ≥500 mL blood loss with ongoing bleeding "wet surgical field"; 5 minutes after NovoSeven (activated FVIIa); at end of surgery before ECMO explantation; upon ICU admission
Coagulation Profile Assessed by Standard Laboratory Tests
Assessment of coagulation status using standard laboratory tests to evaluate differences in hemostatic profiles between LMWH and UFH anticoagulation strategies in ECMO-supported lung transplantation. Blood samples will be analyzed for standard coagulation parameters, including: Activated partial thromboplastin time (aPTT) in seconds. Prothrombin time (PT) in seconds. Thrombin time (TT) in seconds. Fibrinogen levels in g/L. Factor XIII (FXIII) levels in %. D-dimers in mg/L FEU. Fibrin monomers (FM) in mg/L. Antithrombin activity in %. Anti-Xa level in IU/mL. Platelet count x109/L Hemoglobin in g/L.
Time frame: Before anticoagulation administration; 5 minutes after anticoagulation; at ≥500 mL blood loss with ongoing bleeding "wet surgical field"; 5 minutes after NovoSeven (activated FVIIa); at end of surgery before ECMO explantation; upon ICU admission
Plan to share: Yes — Outcome measures (primary and secondary endpoints) Laboratory test results relevant to the study Adverse event data
Supporting information: Study protocol, Informed consent form
Time frame: from march 2025
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