- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04456894
Primary Hemostasis Pathology in Patients on ECMO During Lung Transplantation
Importance of Monitoring Primary Hemostasis Pathology in Patients on Extracorporeal Membrane Oxygenation (ECMO) During Lung Transplantation
Study Overview
Status
Conditions
Detailed Description
ECMO is a type of extracorporeal circulation that has experienced a significant increase in use in the last decade as a substitute for lung or heart functions in patients, both perioperatively - especially extensive thoracic surgery procedures such as lung transplantation, or in resuscitation care - in life-threatening conditions associated with heart or lung failure. It uses the classical principle of extracorporeal circulation technology to create continuous, non-pulsating blood flow and, at the same time, its extracorporeal oxygenation. In its two basic configurations, it can only be used to provide respiratory support (veno-venous configuration, VV ECMO), or also cardiac support (veno-arterial configuration, VA ECMO).
Due to the fact that ECMO circuit is an artificial system consisting of cannulas, blood pump and oxygenator itself, the blood is exposed to a huge surface that is not covered by endothelium, thus stimulates the activation of proinflammatory and procoagulant systems. This exposure results in a prothrombotic condition that is associated with a high risk of thrombotic complications. At the same time, however, with this continuous activation of the coagulation cascade, platelets and coagulation factors are depleted, this may lead to an increased risk of bleeding. Pathological shear stress may result in direct binding of VWF (von Willebrand factor) and the platelet GPIIb / IIIa receptor, resulting in their activation and thrombotic complications, however, the effect of non-physiological shear stress may also lead to loss of GPIbα and GPVI platelet receptors, which, in the opposite, causes a disorder of their adhesion and aggregation to VWF and collagen and increases risk of bleeding. Another important factor is loss and fragmentation of the large VWF multimers, a condition known as acquired von Willebrand's syndrome, which causes platelet adhesion to be impaired and thus contributes to bleeding complications.
Both of these situations, definitely, increase morbidity and mortality in patients, so it is necessary to find an optimal and reliable options for the coagulation system functions monitoration, based on which it is possible to immediately perform a targeted therapeutic intervention.
Results of several studies suggest, that increased platelet activation or decreased function results in both thrombotic and bleeding complications in patients requiring extracorporeal support, and these changes cannot be detected by tests, which are usually performed (ROTEM or other common coagulation tests).
Hypothesis:
ECMO causes an early disorder of primary hemostasis, which is detectable by point of care (POC) testing methods PFA 200 and ROTEM / platelet, according to their results, targeted and effective therapy can be applied.
Objectives:
Primary objective is to find out:
- whether ECMO implantation leads to an early failure of primary hemostasis, which can be diagnosed by POC examination - PFA 200, Rotem / platelet-aggregometry and von Willebrand factor levels.
- whether targeted therapy of primary hemostasis disorders (based on the results of POC tests) leads to normalization of these tests results and cessation of bleeding
Secondary objectives:
- to determine the extent of correlation of POC tests of primary hemostasis and laboratory examination of VWF function and quantity
- to clarify the correlation between possible pathological values of these tests and clinically significant bleeding in the patient
- identification of the most reliable method for the assessment of primary hemostasis
Methods:
The group of patients will be represented by patients indicated for implantation of ECMO support during the lung transplantation procedure. ROTEM, PFA 200 and ROTEM / platelet POCs will be used for the perioperative detection of primary and secondary hemostasis disorders- this is a standard approach in Motol University Hospital. In addition to these standard tests, an analysis of the blood sample will also be performed in cooperation with the Institute of hematology and blood transfusion. These tests are represented by quantification of vFW (using quantification of vWF antigen), vFW function test - Ristocetin Cofactor Assay (ex vivo examination of patient's blood plasma, which is depleted of platelets but contains vWF) and Colagen Binding Assay (measures the ability of VWF, especially its large multimers, to bind to collagen).
Blood samples will be taken:
- after induction into general anesthesia
- shortly (15-60 minutes) after ECMO initiation
- shortly (10 minutes) after administration of aimed therapy (vWF or platelets)
- shortly after ECMO explantation (during admission to the ICU, approximatelly 60 minutes after explantation) An informed consent will be signed with the patient prior to lung transplantation.
Time schedule: 1 year (i.e. 40 patients, on average, about 35 patients undergo lung transplantation per year at our department).
Study Type
Enrollment (Actual)
Contacts and Locations
Study Contact
- Name: Miroslav Durila, MD
- Phone Number: 00420224435400
- Email: miroslav.durila@fnmotol.cz
Study Contact Backup
- Name: Michal Garaj, MD
- Phone Number: 00420224435400
- Email: michal.garaj@fnmotol.cz
Study Locations
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Česká Republika
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Prague, Česká Republika, Czechia, 150 06
- UH Motol
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Sampling Method
Study Population
Description
Inclusion Criteria:
- All patients undergoing elective bilateral lung transplantation on ECMO
Exclusion Criteria:
- patients on dual antiplatelets therapy or patients with vWF disease
Study Plan
How is the study designed?
Design Details
- Observational Models: Cohort
- Time Perspectives: Prospective
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
To find out whether ECMO implantation leads to an early failure of primary hemostasis, which can be diagnosed by POC examination - PFA 200, Rotem / platelet-aggregometry and von Willebrand factor levels
Time Frame: 1 year
|
To compare primary hemostasis before and after ECMO implantation
|
1 year
|
To find out whether targeted therapy of primary hemostasis disorders (based on the results of POC tests) leads to normalization of these tests results and cessation of bleeding
Time Frame: 1 year
|
To evaluate whether aimed therapy based on results of POC tests leads to improvement of test results and bleeding
|
1 year
|
To find out whether aimed treatment during ECMO will be effective or whether primary hemostasis pathology can be by-passed by activated FVIIa
Time Frame: 1 year
|
In case that aimed therapy does not stop bleeding or improved POC tests, activated FVIIa in small dose of 15-30 ug/kg can be used to ,,by-pass" primary hemostasis
|
1 year
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
To determine the extent of correlation of POC tests of primary hemostasis and laboratory examination of VWF function and quantity
Time Frame: 1 year
|
1 year
|
To identify the most reliable method for the assessment of primary hemostasis
Time Frame: 1 year
|
1 year
|
Collaborators and Investigators
Sponsor
Publications and helpful links
General Publications
- Lafc G, Budak AB, Yener AU, Cicek OF. Use of extracorporeal membrane oxygenation in adults. Heart Lung Circ. 2014 Jan;23(1):10-23. doi: 10.1016/j.hlc.2013.08.009. Epub 2013 Sep 1.
- Hayanga JWA, Chan EG, Musgrove K, Leung A, Shigemura N, Hayanga HK. Extracorporeal Membrane Oxygenation in the Perioperative Care of the Lung Transplant Patient. Semin Cardiothorac Vasc Anesth. 2020 Mar;24(1):45-53. doi: 10.1177/1089253219896123. Epub 2020 Jan 2.
- Chen Z, Mondal NK, Ding J, Koenig SC, Slaughter MS, Wu ZJ. Paradoxical Effect of Nonphysiological Shear Stress on Platelets and von Willebrand Factor. Artif Organs. 2016 Jul;40(7):659-68. doi: 10.1111/aor.12606. Epub 2015 Nov 18.
- Balle CM, Jeppesen AN, Christensen S, Hvas AM. Platelet Function During Extracorporeal Membrane Oxygenation in Adult Patients. Front Cardiovasc Med. 2019 Aug 8;6:114. doi: 10.3389/fcvm.2019.00114. eCollection 2019.
- Heilmann C, Geisen U, Beyersdorf F, Nakamura L, Benk C, Trummer G, Berchtold-Herz M, Schlensak C, Zieger B. Acquired von Willebrand syndrome in patients with extracorporeal life support (ECLS). Intensive Care Med. 2012 Jan;38(1):62-8. doi: 10.1007/s00134-011-2370-6. Epub 2011 Oct 1.
- Chen Z, Mondal NK, Zheng S, Koenig SC, Slaughter MS, Griffith BP, Wu ZJ. High shear induces platelet dysfunction leading to enhanced thrombotic propensity and diminished hemostatic capacity. Platelets. 2019;30(1):112-119. doi: 10.1080/09537104.2017.1384542. Epub 2017 Nov 28.
- Favaloro EJ. Clinical utility of the PFA-100. Semin Thromb Hemost. 2008 Nov;34(8):709-33. doi: 10.1055/s-0029-1145254. Epub 2009 Feb 12.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Other Study ID Numbers
- 01072020
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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