<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04456894</url>
  </required_header>
  <id_info>
    <org_study_id>01072020</org_study_id>
    <nct_id>NCT04456894</nct_id>
  </id_info>
  <brief_title>Primary Hemostasis Pathology in Patients on ECMO During Lung Transplantation</brief_title>
  <official_title>Importance of Monitoring Primary Hemostasis Pathology in Patients on Extracorporeal Membrane Oxygenation (ECMO) During Lung Transplantation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Hospital, Motol</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University Hospital, Motol</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Lung transplantation is a very long and difficult procedure accompanied by a number of&#xD;
      possible complications. In the vast majority of cases, the operation itself is performed&#xD;
      using the ECMO support, which can negatively affect blood clotting, especially the formation&#xD;
      of a platelet blood clot, i.e. primary hemostasis. Thus, the procedure may be accompanied by&#xD;
      considerable blood loss, which amount can subsequently negatively affect the postoperative&#xD;
      period. It can be assumed, that precise diagnosis of primary hemostasis disorders and&#xD;
      subsequent targeted therapy can reduce blood loss and improve outcome of the patient.&#xD;
      However, the role of primary hemostasis has not yet been sufficiently specified in this area.&#xD;
      Usually, coagulation functions during surgery, are at our department monitored by using ROTEM&#xD;
      tests (assesses clot strength), PFA 200 (assesses primary haemostasis under high shear stress&#xD;
      conditions and is very sensitive to vWF deficiency) and ROTEM / platelet (assesses primary&#xD;
      haemostasis under &quot;low shear stress&quot; conditions and is very susceptible to platelet&#xD;
      dysfunction). Targeted therapy by administering necessary clotting factors is used, if any&#xD;
      pathology in these tests is detected. However, it is not known, whether the targeted therapy&#xD;
      administered is effective enough in patients during the support of extracorporeal&#xD;
      circulation. In our monocentric, prospective, observational study, data from the tests&#xD;
      mentioned above will be analyzed, and their correlation with a laboratory examination of VWF&#xD;
      levels and activity will be monitored. Based on these data, we will try to determine whether&#xD;
      perioperative examination of primary hemostasis during lung transplantation (PFA examination,&#xD;
      Rotem / platelet-aggregometry and von Willebrand factor-vWF level) is of clinical&#xD;
      significance and whether the diagnosis of hemostasis disorder at this level and subsequent&#xD;
      targeted therapy may reduce perioperative blood loss.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      ECMO is a type of extracorporeal circulation that has experienced a significant increase in&#xD;
      use in the last decade as a substitute for lung or heart functions in patients, both&#xD;
      perioperatively - especially extensive thoracic surgery procedures such as lung&#xD;
      transplantation, or in resuscitation care - in life-threatening conditions associated with&#xD;
      heart or lung failure. It uses the classical principle of extracorporeal circulation&#xD;
      technology to create continuous, non-pulsating blood flow and, at the same time, its&#xD;
      extracorporeal oxygenation. In its two basic configurations, it can only be used to provide&#xD;
      respiratory support (veno-venous configuration, VV ECMO), or also cardiac support&#xD;
      (veno-arterial configuration, VA ECMO).&#xD;
&#xD;
      Due to the fact that ECMO circuit is an artificial system consisting of cannulas, blood pump&#xD;
      and oxygenator itself, the blood is exposed to a huge surface that is not covered by&#xD;
      endothelium, thus stimulates the activation of proinflammatory and procoagulant systems. This&#xD;
      exposure results in a prothrombotic condition that is associated with a high risk of&#xD;
      thrombotic complications. At the same time, however, with this continuous activation of the&#xD;
      coagulation cascade, platelets and coagulation factors are depleted, this may lead to an&#xD;
      increased risk of bleeding. Pathological shear stress may result in direct binding of VWF&#xD;
      (von Willebrand factor) and the platelet GPIIb / IIIa receptor, resulting in their activation&#xD;
      and thrombotic complications, however, the effect of non-physiological shear stress may also&#xD;
      lead to loss of GPIbα and GPVI platelet receptors, which, in the opposite, causes a disorder&#xD;
      of their adhesion and aggregation to VWF and collagen and increases risk of bleeding. Another&#xD;
      important factor is loss and fragmentation of the large VWF multimers, a condition known as&#xD;
      acquired von Willebrand's syndrome, which causes platelet adhesion to be impaired and thus&#xD;
      contributes to bleeding complications.&#xD;
&#xD;
      Both of these situations, definitely, increase morbidity and mortality in patients, so it is&#xD;
      necessary to find an optimal and reliable options for the coagulation system functions&#xD;
      monitoration, based on which it is possible to immediately perform a targeted therapeutic&#xD;
      intervention.&#xD;
&#xD;
      Results of several studies suggest, that increased platelet activation or decreased function&#xD;
      results in both thrombotic and bleeding complications in patients requiring extracorporeal&#xD;
      support, and these changes cannot be detected by tests, which are usually performed (ROTEM or&#xD;
      other common coagulation tests).&#xD;
&#xD;
      Hypothesis:&#xD;
&#xD;
      ECMO causes an early disorder of primary hemostasis, which is detectable by point of care&#xD;
      (POC) testing methods PFA 200 and ROTEM / platelet, according to their results, targeted and&#xD;
      effective therapy can be applied.&#xD;
&#xD;
      Objectives:&#xD;
&#xD;
      Primary objective is to find out:&#xD;
&#xD;
        -  whether ECMO implantation leads to an early failure of primary hemostasis, which can be&#xD;
           diagnosed by POC examination - PFA 200, Rotem / platelet-aggregometry and von Willebrand&#xD;
           factor levels.&#xD;
&#xD;
        -  whether targeted therapy of primary hemostasis disorders (based on the results of POC&#xD;
           tests) leads to normalization of these tests results and cessation of bleeding&#xD;
&#xD;
      Secondary objectives:&#xD;
&#xD;
        -  to determine the extent of correlation of POC tests of primary hemostasis and laboratory&#xD;
           examination of VWF function and quantity&#xD;
&#xD;
        -  to clarify the correlation between possible pathological values of these tests and&#xD;
           clinically significant bleeding in the patient&#xD;
&#xD;
        -  identification of the most reliable method for the assessment of primary hemostasis&#xD;
&#xD;
      Methods:&#xD;
&#xD;
      The group of patients will be represented by patients indicated for implantation of ECMO&#xD;
      support during the lung transplantation procedure. ROTEM, PFA 200 and ROTEM / platelet POCs&#xD;
      will be used for the perioperative detection of primary and secondary hemostasis disorders-&#xD;
      this is a standard approach in Motol University Hospital. In addition to these standard&#xD;
      tests, an analysis of the blood sample will also be performed in cooperation with the&#xD;
      Institute of hematology and blood transfusion. These tests are represented by quantification&#xD;
      of vFW (using quantification of vWF antigen), vFW function test - Ristocetin Cofactor Assay&#xD;
      (ex vivo examination of patient's blood plasma, which is depleted of platelets but contains&#xD;
      vWF) and Colagen Binding Assay (measures the ability of VWF, especially its large multimers,&#xD;
      to bind to collagen).&#xD;
&#xD;
      Blood samples will be taken:&#xD;
&#xD;
        1. after induction into general anesthesia&#xD;
&#xD;
        2. shortly (15-60 minutes) after ECMO initiation&#xD;
&#xD;
        3. shortly (10 minutes) after administration of aimed therapy (vWF or platelets)&#xD;
&#xD;
        4. shortly after ECMO explantation (during admission to the ICU, approximatelly 60 minutes&#xD;
           after explantation) An informed consent will be signed with the patient prior to lung&#xD;
           transplantation.&#xD;
&#xD;
      Time schedule: 1 year (i.e. 40 patients, on average, about 35 patients undergo lung&#xD;
      transplantation per year at our department).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 7, 2020</start_date>
  <completion_date type="Actual">August 15, 2023</completion_date>
  <primary_completion_date type="Actual">August 15, 2023</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>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</measure>
    <time_frame>1 year</time_frame>
    <description>To compare primary hemostasis before and after ECMO implantation</description>
  </primary_outcome>
  <primary_outcome>
    <measure>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</measure>
    <time_frame>1 year</time_frame>
    <description>To evaluate whether aimed therapy based on results of POC tests leads to improvement of test results and bleeding</description>
  </primary_outcome>
  <primary_outcome>
    <measure>To find out whether aimed treatment during ECMO will be effective or whether primary hemostasis pathology can be by-passed by activated FVIIa</measure>
    <time_frame>1 year</time_frame>
    <description>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&quot; primary hemostasis</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>To determine the extent of correlation of POC tests of primary hemostasis and laboratory examination of VWF function and quantity</measure>
    <time_frame>1 year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To identify the most reliable method for the assessment of primary hemostasis</measure>
    <time_frame>1 year</time_frame>
  </secondary_outcome>
  <enrollment type="Actual">36</enrollment>
  <condition>ECMO Primary Hemostasis Pathology</condition>
  <eligibility>
    <study_pop>
      <textblock>
        Patients on waiting list for planned lung transplantation procedure. Patients with COPD,&#xD;
        cystic fibrosis, interstitial pulmonary fibrosis, primary pulmonary hypertension&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  All patients undergoing elective bilateral lung transplantation on ECMO&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  patients on dual antiplatelets therapy or patients with vWF disease&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>UH Motol</name>
      <address>
        <city>Prague</city>
        <state>Česká Republika</state>
        <zip>150 06</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Czechia</country>
  </location_countries>
  <reference>
    <citation>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.</citation>
    <PMID>24144910</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>31893982</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>26582038</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>31440518</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>21965100</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>29182470</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>19214910</PMID>
  </reference>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>July 1, 2020</study_first_submitted>
  <study_first_submitted_qc>July 1, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 7, 2020</study_first_posted>
  <last_update_submitted>August 15, 2023</last_update_submitted>
  <last_update_submitted_qc>August 15, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 16, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University Hospital, Motol</investigator_affiliation>
    <investigator_full_name>Durila Miroslav MUDr. Ph.D.</investigator_full_name>
    <investigator_title>assoc.prof. MD. Miroslav Durila, PhD.</investigator_title>
  </responsible_party>
  <keyword>ECMO</keyword>
  <keyword>PFA 200</keyword>
  <keyword>ROTEMplatelets</keyword>
  <keyword>bleeding</keyword>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04456894
org study id: 01072020
nct id: NCT04456894
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
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, i.e. 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.
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:

        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 (i.e. 40 patients, on average, about 35 patients undergo lung
      transplantation per year at our department).
observational model: Cohort
time perspective: Prospective
measure: 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
description: To compare primary hemostasis before and after ECMO implantation
measure: 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
description: To evaluate whether aimed therapy based on results of POC tests leads to improvement of test results and bleeding
measure: 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
description: 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
measure: To determine the extent of correlation of POC tests of primary hemostasis and laboratory examination of VWF function and quantity
time frame: 1 year
measure: To identify the most reliable method for the assessment of primary hemostasis
time frame: 1 year
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
facility: 
country: Czechia
citation: 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.
PMID: 24144910
citation: 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.
PMID: 31893982
citation: 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.
PMID: 26582038
citation: 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.
PMID: 31440518
citation: 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.
PMID: 21965100
citation: 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.
PMID: 29182470
citation: 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.
PMID: 19214910
responsible party type: Principal Investigator
investigator affiliation: University Hospital, Motol
investigator full name: Durila Miroslav MUDr. Ph.D.
investigator title: assoc.prof. MD. Miroslav Durila, PhD.