Ignite Creation Date:
2024-05-06 @ 2:52 PM
Last Modification Date:
2024-10-26 @ 1:39 PM
Study NCT ID:
NCT04456894
Status:
COMPLETED
Last Update Posted:
2023-08-16
First Post:
2020-07-01
Brief Title:
Primary Hemostasis Pathology in Patients on ECMO During Lung Transplantation
Sponsor:
University Hospital Motol
Organization:
University Hospital Motol
Study Overview
Official Title:
Importance of Monitoring Primary Hemostasis Pathology in Patients on Extracorporeal Membrane Oxygenation ECMO During Lung Transplantation
Status:
COMPLETED
Status Verified Date:
2024-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Lung transplantation is a very long and difficult procedure accompanied by a number of possible complications In the vast majority of cases the operation itself is performed using the ECMO support which can negatively affect blood clotting especially the formation of a platelet blood clot ie primary hemostasis Thus the procedure may be accompanied by considerable blood loss which amount can subsequently negatively affect the postoperative period It can be assumed that precise diagnosis of primary hemostasis disorders and subsequent targeted therapy can reduce blood loss and improve outcome of the patient However the role of primary hemostasis has not yet been sufficiently specified in this area Usually coagulation functions during surgery are at our department monitored by using ROTEM tests assesses clot strength PFA 200 assesses primary haemostasis under high shear stress conditions and is very sensitive to vWF deficiency and ROTEM platelet assesses primary haemostasis under low shear stress conditions and is very susceptible to platelet dysfunction Targeted therapy by administering necessary clotting factors is used if any pathology in these tests is detected However it is not known whether the targeted therapy administered is effective enough in patients during the support of extracorporeal circulation In our monocentric prospective observational study data from the tests mentioned above will be analyzed and their correlation with a laboratory examination of VWF levels and activity will be monitored Based on these data we will try to determine whether perioperative examination of primary hemostasis during lung transplantation PFA examination Rotem platelet-aggregometry and von Willebrand factor-vWF level is of clinical significance and whether the diagnosis of hemostasis disorder at this level and subsequent targeted therapy may reduce perioperative blood loss
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 Willebrands 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 patients 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
1 after induction into general anesthesia
2 shortly 15-60 minutes after ECMO initiation
3 shortly 10 minutes after administration of aimed therapy vWF or platelets
4 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 ie 40 patients on average about 35 patients undergo lung transplantation per year at our department
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 Willebrands 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 patients 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
1 after induction into general anesthesia
2 shortly 15-60 minutes after ECMO initiation
3 shortly 10 minutes after administration of aimed therapy vWF or platelets
4 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 ie 40 patients on average about 35 patients undergo lung transplantation per year at our department
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None