<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/NCT02991066</url>
  </required_header>
  <id_info>
    <org_study_id>1309</org_study_id>
    <nct_id>NCT02991066</nct_id>
  </id_info>
  <brief_title>Role of Microparticles in the Coagulopathy of Acute Promyelocytic Leukemia</brief_title>
  <official_title>Role of Microparticles in the Coagulopathy of Acute Promyelocytic Leukemia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>First Affiliated Hospital of Harbin Medical University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>First Affiliated Hospital of Harbin Medical University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Although the clinical application of differentiation therapy has made great success in the&#xD;
      treatment of acute promyelocytic leukemia (APL), early fatal bleeding remains an unsolved&#xD;
      problem which accounts for the main reason of induction failure in APL patients. The clinical&#xD;
      manifestation of both serious bleeding and thrombosis illustrate the complexity of the&#xD;
      pathogenesis of coagulopathy in APL. Despite extensive research, the pathogenesis of&#xD;
      coagulopathy in APL is still unclear. Microparticles, 0.11μm in diameter, are small membrane&#xD;
      vesicles released to circulation by blood cells and vascular endothelial cells during&#xD;
      activation or apoptosis. Microparticles (MPs) derived from different cells types all exert&#xD;
      procoagulant activity mediated by phosphatidylserine (PS) and carry some basic substances&#xD;
      derived from their origin cells. Also, the biological activity of microparticles is often&#xD;
      significantly higher than that of the cells they come from. According to these problems and&#xD;
      background knowledge, our project aims to observe the roles of microparticles derived from&#xD;
      APL cells and the procoagulant or profibrinolytic activating factors resided on these&#xD;
      microparticles in the pathogenesis of coagulopathy in APL, and the effects of different&#xD;
      induction therapies, chemotherapeutic drugs or differentiation agents on these microparticles&#xD;
      and their procoagulant or profibrinolytic activating factors. To carry out this study,&#xD;
      microparticles are obtained from patients who undergo different induction therapies at&#xD;
      different time points or from primary bone marrow APL cells which are treated by different&#xD;
      drugs in vitro at different time points, the expressions and activities of five procoagulant&#xD;
      or profibrinolytic activating factors, which are highly expressed in APL cells, PS exposure&#xD;
      and the functional state of these microparticles, will be dynamically monitored. Further&#xD;
      study of the pathogenesis of coagulopathy in APL can provide clues and help for deep&#xD;
      understanding of clinical manifestations, guiding clinical treatment as well as judging&#xD;
      prognosis, and establishing theoretical basis for exploring new treatment.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The investigators plan to measure routine laboratory parameters of coagulation and&#xD;
      fibrinolysis, the procoagulant or profibrinolytic activity of microparticles (MPs), and&#xD;
      explore the role of the procoagulant and profibrinolytic activating factor of MPs in the&#xD;
      pathogenesis of coagulopathy in patients with APL.&#xD;
&#xD;
      i. Dynamic turbidimetry of plasma clot formation. The effects of MPs on the kinetics of&#xD;
      fibrin formation and on the optical properties of clots are studied using dynamic&#xD;
      turbidimetry of re-calcified plasma samples (platelet-free plasma and microparticle-depleted&#xD;
      plasma) without adding any clotting activator. Clotting of plasma samples induced by Ca2+ is&#xD;
      followed by monitoring the optical density at λ = 405 nm at 37 °C.&#xD;
&#xD;
      ii. Thrombin generation assay. The amount of thrombin formed in plasma upon re-calcification&#xD;
      is measured directly using a modified thrombin generation test . Because fibrin interferes&#xD;
      with colorimetric measurements, plasma samples are first defibrinated by adding reptilase&#xD;
      followed by incubation at 37 °C. The clots are removed. Then a chromogenic substrate for&#xD;
      thrombin is added to the plasma samples. Thrombin generation is started by adding CaCl2 with&#xD;
      simultaneous recording of the absorbance at λ = 405 nm.&#xD;
&#xD;
      iii. Thrombin generating capacity of the MPs. MPs are reconstituted in defibrinated&#xD;
      (reptilase treated), normal pooled microparticle-depleted plasma. Then a chromogenic&#xD;
      substrate for thrombin is added to the samples. Thrombin generation is started by adding&#xD;
      CaCl2 with simultaneous recording of the absorbance at λ = 405 nm.&#xD;
&#xD;
      iv. Thrombin generation inhibitory experiments. The following inhibitors are pre-incubated&#xD;
      with the microparticles: Annexin V, anti-human tissue factor (TF) and irrelevant control&#xD;
      immunoglobulin G (IgG). Then repeats the experiment iii.&#xD;
&#xD;
      v. Fibrinolytic activity. Incubate a fixed concentration of plasminogen with the plasma&#xD;
      samples in the presence of a chromogenic substrate selective for plasmin. Plasmin formed from&#xD;
      plasminogen bound at the surface of microparticles cleaves the chromogenic substrate and the&#xD;
      released p-nitroaniline is detected by measuring A405nm as a function of time.&#xD;
&#xD;
      vi. Determination of fibrinolytic activity on microparticles. The capacity of microparticles&#xD;
      to activate plasminogen is determined by incubating a fixed concentration of plasminogen&#xD;
      (1mM) with the microparticles with or without t-PA and/or u-PA in the presence of a&#xD;
      chromogenic substrate selective for plasmin. Plasmin formed from plasminogen bound at the&#xD;
      surface of microparticles cleaves the chromogenic substrate and the released p-nitroaniline&#xD;
      is detected by measuring A405nm.&#xD;
&#xD;
      vii. Fibrinolytic activity inhibitory experiments. The following inhibitors are pre-incubated&#xD;
      with the microparticles: anti-human tissue type plasminogen activator (tPA) , anti-human&#xD;
      urokinase type plasminogen activator (uPA), and respective irrelevant control IgGs;&#xD;
      ε-aminocaproic acid and plasminogen activator inhibitor-1 (PAI-1).Then repeat the experiment&#xD;
      vi.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>October 2014</start_date>
  <completion_date type="Anticipated">December 2020</completion_date>
  <primary_completion_date type="Anticipated">December 2019</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Control</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Change From Baseline in the Levels and Cellular Origin of MPs at 5 Weeks</measure>
    <time_frame>5 weeks</time_frame>
    <description>Demonstration that the some procoagulant or profibrinolytic activating factors expressed on MP in APL patients' plasma associate with the thrombin generating capacity and fibrinolytic activity of patients' plasma.</description>
  </primary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Anticipated">20</enrollment>
  <condition>Acute Promyelocytic Leukemia</condition>
  <arm_group>
    <arm_group_label>Patients</arm_group_label>
    <description>patients with de novo acute promyelocytic leukemia with hemorrhage.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control</arm_group_label>
    <description>healthy volunteers.</description>
  </arm_group>
  <biospec_retention>Samples Without DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Venous blood from patients with acute promyelocytic leukemia and from healthy volunteers is&#xD;
      collected into 0.119M sodium citrate Vacuum tubes. platelet-free plasma is prepared within 4h&#xD;
      using 2 serial centrifugations ( 15min at 1,500g, 2 min at 13,000g) and stored at -80℃ until&#xD;
      use. A portion of PFP was filtered through a 0.1-um-pore size filter to collect&#xD;
      microparticle-depleted plasma and stored at -80℃ until use. Experiments concerning&#xD;
      procoagulant activity are detected immediately after blood collection.&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        patients with acute promyelocytic leukemia&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients with de novo APL accompanied by hemorrhage.&#xD;
&#xD;
          -  The diagnosis was confirmed by the presence of t(15;17) and/or the PML (promyelocytic&#xD;
             leukemia)/RARa(retinoic acid receptor alpha) fusion gene.&#xD;
&#xD;
          -  Patients should receive single-agent arsenic trioxide (ATO) for induction therapy.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients with relapsed acute promyelocytic leukemia.&#xD;
&#xD;
          -  Patients without evidence of bleeding.&#xD;
&#xD;
          -  Patients younger than 18 years.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jin Zhou, MD, PhD</last_name>
    <role>Study Chair</role>
    <affiliation>First Affiliated Hospital of Harbin Medical University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Jin Zhou, MD, PhD</last_name>
    <phone>008645185555951</phone>
    <email>zhoujin1111@126.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>the First Affiliated Hospital of Harbin Medical University</name>
      <address>
        <city>Harbin</city>
        <state>Heilongjiang</state>
        <zip>150001</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jin Zhou, MD, PhD</last_name>
      <phone>008645185555951</phone>
      <email>zhoujin1111@126.com</email>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <reference>
    <citation>de la Serna J, Montesinos P, Vellenga E, Rayon C, Parody R, Leon A, Esteve J, Bergua JM, Milone G, Deben G, Rivas C, Gonzalez M, Tormo M, Diaz-Mediavilla J, Gonzalez JD, Negri S, Amutio E, Brunet S, Lowenberg B, Sanz MA. Causes and prognostic factors of remission induction failure in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and idarubicin. Blood. 2008 Apr 1;111(7):3395-402. doi: 10.1182/blood-2007-07-100669. Epub 2008 Jan 14.</citation>
    <PMID>18195095</PMID>
  </reference>
  <reference>
    <citation>Jacomo RH, Melo RA, Souto FR, de Mattos ER, de Oliveira CT, Fagundes EM, Bittencourt HN, Bittencourt RI, Bortolheiro TC, Paton EJ, Bendlin R, Ismael S, Chauffaille Mde L, Silva D, Pagnano KB, Ribeiro R, Rego EM. Clinical features and outcomes of 134 Brazilians with acute promyelocytic leukemia who received ATRA and anthracyclines. Haematologica. 2007 Oct;92(10):1431-2. doi: 10.3324/haematol.10874.</citation>
    <PMID>18024380</PMID>
  </reference>
  <reference>
    <citation>Dally N, Hoffman R, Haddad N, Sarig G, Rowe JM, Brenner B. Predictive factors of bleeding and thrombosis during induction therapy in acute promyelocytic leukemia-a single center experience in 34 patients. Thromb Res. 2005;116(2):109-14. doi: 10.1016/j.thromres.2004.11.001. Epub 2005 Jan 12.</citation>
    <PMID>15907524</PMID>
  </reference>
  <reference>
    <citation>Breccia M, Avvisati G, Latagliata R, Carmosino I, Guarini A, De Propris MS, Gentilini F, Petti MC, Cimino G, Mandelli F, Lo-Coco F. Occurrence of thrombotic events in acute promyelocytic leukemia correlates with consistent immunophenotypic and molecular features. Leukemia. 2007 Jan;21(1):79-83. doi: 10.1038/sj.leu.2404377. Epub 2006 Aug 24.</citation>
    <PMID>16932337</PMID>
  </reference>
  <reference>
    <citation>Tapiovaara H, Alitalo R, Stephens R, Myohanen H, Ruutu T, Vaheri A. Abundant urokinase activity on the surface of mononuclear cells from blood and bone marrow of acute leukemia patients. Blood. 1993 Aug 1;82(3):914-9.</citation>
    <PMID>8338954</PMID>
  </reference>
  <reference>
    <citation>Menell JS, Cesarman GM, Jacovina AT, McLaughlin MA, Lev EA, Hajjar KA. Annexin II and bleeding in acute promyelocytic leukemia. N Engl J Med. 1999 Apr 1;340(13):994-1004. doi: 10.1056/NEJM199904013401303.</citation>
    <PMID>10099141</PMID>
  </reference>
  <reference>
    <citation>Liu Y, Wang Z, Jiang M, Dai L, Zhang W, Wu D, Ruan C. The expression of annexin II and its role in the fibrinolytic activity in acute promyelocytic leukemia. Leuk Res. 2011 Jul;35(7):879-84. doi: 10.1016/j.leukres.2010.11.008. Epub 2010 Dec 10.</citation>
    <PMID>21146216</PMID>
  </reference>
  <reference>
    <citation>Sinauridze EI, Kireev DA, Popenko NY, Pichugin AV, Panteleev MA, Krymskaya OV, Ataullakhanov FI. Platelet microparticle membranes have 50- to 100-fold higher specific procoagulant activity than activated platelets. Thromb Haemost. 2007 Mar;97(3):425-34.</citation>
    <PMID>17334510</PMID>
  </reference>
  <reference>
    <citation>Bach RR. Tissue factor encryption. Arterioscler Thromb Vasc Biol. 2006 Mar;26(3):456-61. doi: 10.1161/01.ATV.0000202656.53964.04. Epub 2006 Jan 5.</citation>
    <PMID>16397140</PMID>
  </reference>
  <reference>
    <citation>Hron G, Kollars M, Weber H, Sagaster V, Quehenberger P, Eichinger S, Kyrle PA, Weltermann A. Tissue factor-positive microparticles: cellular origin and association with coagulation activation in patients with colorectal cancer. Thromb Haemost. 2007 Jan;97(1):119-23.</citation>
    <PMID>17200778</PMID>
  </reference>
  <reference>
    <citation>Tesselaar ME, Romijn FP, Van Der Linden IK, Prins FA, Bertina RM, Osanto S. Microparticle-associated tissue factor activity: a link between cancer and thrombosis? J Thromb Haemost. 2007 Mar;5(3):520-7. doi: 10.1111/j.1538-7836.2007.02369.x. Epub 2006 Dec 13.</citation>
    <PMID>17166244</PMID>
  </reference>
  <reference>
    <citation>Biro E, Sturk-Maquelin KN, Vogel GM, Meuleman DG, Smit MJ, Hack CE, Sturk A, Nieuwland R. Human cell-derived microparticles promote thrombus formation in vivo in a tissue factor-dependent manner. J Thromb Haemost. 2003 Dec;1(12):2561-8. doi: 10.1046/j.1538-7836.2003.00456.x.</citation>
    <PMID>14738565</PMID>
  </reference>
  <reference>
    <citation>Pereira J, Alfaro G, Goycoolea M, Quiroga T, Ocqueteau M, Massardo L, Perez C, Saez C, Panes O, Matus V, Mezzano D. Circulating platelet-derived microparticles in systemic lupus erythematosus. Association with increased thrombin generation and procoagulant state. Thromb Haemost. 2006 Jan;95(1):94-9.</citation>
    <PMID>16543967</PMID>
  </reference>
  <reference>
    <citation>Kwaan HC, Rego EM. Role of microparticles in the hemostatic dysfunction in acute promyelocytic leukemia. Semin Thromb Hemost. 2010 Nov;36(8):917-24. doi: 10.1055/s-0030-1267045. Epub 2010 Nov 3.</citation>
    <PMID>21049391</PMID>
  </reference>
  <verification_date>April 2018</verification_date>
  <study_first_submitted>March 2, 2016</study_first_submitted>
  <study_first_submitted_qc>December 8, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 13, 2016</study_first_posted>
  <last_update_submitted>April 22, 2018</last_update_submitted>
  <last_update_submitted_qc>April 22, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">April 24, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Acute promyelocytic leukemia</keyword>
  <keyword>Coagulopathy</keyword>
  <keyword>Microparticles</keyword>
  <keyword>Mechanism</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Leukemia</mesh_term>
    <mesh_term>Leukemia, Promyelocytic, Acute</mesh_term>
    <mesh_term>Hemostatic Disorders</mesh_term>
    <mesh_term>Blood Coagulation Disorders</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
  </patient_data>
  <!-- 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/NCT02991066
org study id: 1309
nct id: NCT02991066
lead sponsor: 
has dmc: No
Although the clinical application of differentiation therapy has made great success in the
      treatment of acute promyelocytic leukemia (APL), early fatal bleeding remains an unsolved
      problem which accounts for the main reason of induction failure in APL patients. The clinical
      manifestation of both serious bleeding and thrombosis illustrate the complexity of the
      pathogenesis of coagulopathy in APL. Despite extensive research, the pathogenesis of
      coagulopathy in APL is still unclear. Microparticles, 0.11μm in diameter, are small membrane
      vesicles released to circulation by blood cells and vascular endothelial cells during
      activation or apoptosis. Microparticles (MPs) derived from different cells types all exert
      procoagulant activity mediated by phosphatidylserine (PS) and carry some basic substances
      derived from their origin cells. Also, the biological activity of microparticles is often
      significantly higher than that of the cells they come from. According to these problems and
      background knowledge, our project aims to observe the roles of microparticles derived from
      APL cells and the procoagulant or profibrinolytic activating factors resided on these
      microparticles in the pathogenesis of coagulopathy in APL, and the effects of different
      induction therapies, chemotherapeutic drugs or differentiation agents on these microparticles
      and their procoagulant or profibrinolytic activating factors. To carry out this study,
      microparticles are obtained from patients who undergo different induction therapies at
      different time points or from primary bone marrow APL cells which are treated by different
      drugs in vitro at different time points, the expressions and activities of five procoagulant
      or profibrinolytic activating factors, which are highly expressed in APL cells, PS exposure
      and the functional state of these microparticles, will be dynamically monitored. Further
      study of the pathogenesis of coagulopathy in APL can provide clues and help for deep
      understanding of clinical manifestations, guiding clinical treatment as well as judging
      prognosis, and establishing theoretical basis for exploring new treatment.
The investigators plan to measure routine laboratory parameters of coagulation and
      fibrinolysis, the procoagulant or profibrinolytic activity of microparticles (MPs), and
      explore the role of the procoagulant and profibrinolytic activating factor of MPs in the
      pathogenesis of coagulopathy in patients with APL.

      i. Dynamic turbidimetry of plasma clot formation. The effects of MPs on the kinetics of
      fibrin formation and on the optical properties of clots are studied using dynamic
      turbidimetry of re-calcified plasma samples (platelet-free plasma and microparticle-depleted
      plasma) without adding any clotting activator. Clotting of plasma samples induced by Ca2+ is
      followed by monitoring the optical density at λ = 405 nm at 37 °C.

      ii. Thrombin generation assay. The amount of thrombin formed in plasma upon re-calcification
      is measured directly using a modified thrombin generation test . Because fibrin interferes
      with colorimetric measurements, plasma samples are first defibrinated by adding reptilase
      followed by incubation at 37 °C. The clots are removed. Then a chromogenic substrate for
      thrombin is added to the plasma samples. Thrombin generation is started by adding CaCl2 with
      simultaneous recording of the absorbance at λ = 405 nm.

      iii. Thrombin generating capacity of the MPs. MPs are reconstituted in defibrinated
      (reptilase treated), normal pooled microparticle-depleted plasma. Then a chromogenic
      substrate for thrombin is added to the samples. Thrombin generation is started by adding
      CaCl2 with simultaneous recording of the absorbance at λ = 405 nm.

      iv. Thrombin generation inhibitory experiments. The following inhibitors are pre-incubated
      with the microparticles: Annexin V, anti-human tissue factor (TF) and irrelevant control
      immunoglobulin G (IgG). Then repeats the experiment iii.

      v. Fibrinolytic activity. Incubate a fixed concentration of plasminogen with the plasma
      samples in the presence of a chromogenic substrate selective for plasmin. Plasmin formed from
      plasminogen bound at the surface of microparticles cleaves the chromogenic substrate and the
      released p-nitroaniline is detected by measuring A405nm as a function of time.

      vi. Determination of fibrinolytic activity on microparticles. The capacity of microparticles
      to activate plasminogen is determined by incubating a fixed concentration of plasminogen
      (1mM) with the microparticles with or without t-PA and/or u-PA in the presence of a
      chromogenic substrate selective for plasmin. Plasmin formed from plasminogen bound at the
      surface of microparticles cleaves the chromogenic substrate and the released p-nitroaniline
      is detected by measuring A405nm.

      vii. Fibrinolytic activity inhibitory experiments. The following inhibitors are pre-incubated
      with the microparticles: anti-human tissue type plasminogen activator (tPA) , anti-human
      urokinase type plasminogen activator (uPA), and respective irrelevant control IgGs;
      ε-aminocaproic acid and plasminogen activator inhibitor-1 (PAI-1).Then repeat the experiment
      vi.
observational model: Case-Control
time perspective: Prospective
measure: Change From Baseline in the Levels and Cellular Origin of MPs at 5 Weeks
time frame: 5 weeks
description: Demonstration that the some procoagulant or profibrinolytic activating factors expressed on MP in APL patients' plasma associate with the thrombin generating capacity and fibrinolytic activity of patients' plasma.
arm group label: Patients
description: patients with de novo acute promyelocytic leukemia with hemorrhage.
arm group label: Control
description: healthy volunteers.
Venous blood from patients with acute promyelocytic leukemia and from healthy volunteers is
      collected into 0.119M sodium citrate Vacuum tubes. platelet-free plasma is prepared within 4h
      using 2 serial centrifugations ( 15min at 1,500g, 2 min at 13,000g) and stored at -80℃ until
      use. A portion of PFP was filtered through a 0.1-um-pore size filter to collect
      microparticle-depleted plasma and stored at -80℃ until use. Experiments concerning
      procoagulant activity are detected immediately after blood collection.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Jin Zhou, MD, PhD
role: Study Chair
affiliation: First Affiliated Hospital of Harbin Medical University
last name: Jin Zhou, MD, PhD
phone: 008645185555951
email: zhoujin1111@126.com
facility: 
status: Recruiting
contact: 
country: China
citation: de la Serna J, Montesinos P, Vellenga E, Rayon C, Parody R, Leon A, Esteve J, Bergua JM, Milone G, Deben G, Rivas C, Gonzalez M, Tormo M, Diaz-Mediavilla J, Gonzalez JD, Negri S, Amutio E, Brunet S, Lowenberg B, Sanz MA. Causes and prognostic factors of remission induction failure in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and idarubicin. Blood. 2008 Apr 1;111(7):3395-402. doi: 10.1182/blood-2007-07-100669. Epub 2008 Jan 14.
PMID: 18195095
citation: Jacomo RH, Melo RA, Souto FR, de Mattos ER, de Oliveira CT, Fagundes EM, Bittencourt HN, Bittencourt RI, Bortolheiro TC, Paton EJ, Bendlin R, Ismael S, Chauffaille Mde L, Silva D, Pagnano KB, Ribeiro R, Rego EM. Clinical features and outcomes of 134 Brazilians with acute promyelocytic leukemia who received ATRA and anthracyclines. Haematologica. 2007 Oct;92(10):1431-2. doi: 10.3324/haematol.10874.
PMID: 18024380
citation: Dally N, Hoffman R, Haddad N, Sarig G, Rowe JM, Brenner B. Predictive factors of bleeding and thrombosis during induction therapy in acute promyelocytic leukemia-a single center experience in 34 patients. Thromb Res. 2005;116(2):109-14. doi: 10.1016/j.thromres.2004.11.001. Epub 2005 Jan 12.
PMID: 15907524
citation: Breccia M, Avvisati G, Latagliata R, Carmosino I, Guarini A, De Propris MS, Gentilini F, Petti MC, Cimino G, Mandelli F, Lo-Coco F. Occurrence of thrombotic events in acute promyelocytic leukemia correlates with consistent immunophenotypic and molecular features. Leukemia. 2007 Jan;21(1):79-83. doi: 10.1038/sj.leu.2404377. Epub 2006 Aug 24.
PMID: 16932337
citation: Tapiovaara H, Alitalo R, Stephens R, Myohanen H, Ruutu T, Vaheri A. Abundant urokinase activity on the surface of mononuclear cells from blood and bone marrow of acute leukemia patients. Blood. 1993 Aug 1;82(3):914-9.
PMID: 8338954
citation: Menell JS, Cesarman GM, Jacovina AT, McLaughlin MA, Lev EA, Hajjar KA. Annexin II and bleeding in acute promyelocytic leukemia. N Engl J Med. 1999 Apr 1;340(13):994-1004. doi: 10.1056/NEJM199904013401303.
PMID: 10099141
citation: Liu Y, Wang Z, Jiang M, Dai L, Zhang W, Wu D, Ruan C. The expression of annexin II and its role in the fibrinolytic activity in acute promyelocytic leukemia. Leuk Res. 2011 Jul;35(7):879-84. doi: 10.1016/j.leukres.2010.11.008. Epub 2010 Dec 10.
PMID: 21146216
citation: Sinauridze EI, Kireev DA, Popenko NY, Pichugin AV, Panteleev MA, Krymskaya OV, Ataullakhanov FI. Platelet microparticle membranes have 50- to 100-fold higher specific procoagulant activity than activated platelets. Thromb Haemost. 2007 Mar;97(3):425-34.
PMID: 17334510
citation: Bach RR. Tissue factor encryption. Arterioscler Thromb Vasc Biol. 2006 Mar;26(3):456-61. doi: 10.1161/01.ATV.0000202656.53964.04. Epub 2006 Jan 5.
PMID: 16397140
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responsible party type: Sponsor
mesh term: Leukemia
mesh term: Leukemia, Promyelocytic, Acute
mesh term: Hemostatic Disorders
mesh term: Blood Coagulation Disorders
sharing ipd: Yes