Role of Microparticles in the Coagulopathy of Acute Promyelocytic Leukemia

NCT02991066 | Unknown

• 1 other identifier: 1309
• Study Type: observational
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Acute Promyelocytic Leukemia

Keywords

Acute promyelocytic leukemia; Coagulopathy; Microparticles; Mechanism

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in the Levels and Cellular Origin of MPs at 5 Weeks

  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.

  5 weeks

Study Arms (2)

Patients

patients with de novo acute promyelocytic leukemia with hemorrhage.

Control

healthy volunteers.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

patients with acute promyelocytic leukemia

You may qualify if:

• Patients with de novo APL accompanied by hemorrhage.
• The diagnosis was confirmed by the presence of t(15;17) and/or the PML (promyelocytic leukemia)/RARa(retinoic acid receptor alpha) fusion gene.
• Patients should receive single-agent arsenic trioxide (ATO) for induction therapy.

You may not qualify if:

• Patients with relapsed acute promyelocytic leukemia.
• Patients without evidence of bleeding.
• Patients younger than 18 years.

Sponsors & Collaborators

• First Affiliated Hospital of Harbin Medical University: lead

Study Sites (1)

the First Affiliated Hospital of Harbin Medical University

Harbin, Heilongjiang, 150001, China

RECRUITING

Related Publications (14)

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  PMID: 15907524 BACKGROUND

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  PMID: 16932337 BACKGROUND

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  PMID: 10099141 BACKGROUND

• 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.

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  PMID: 17334510 BACKGROUND

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  PMID: 16543967 BACKGROUND

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  PMID: 21049391 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

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.

MeSH Terms

Conditions

Leukemia, Promyelocytic, Acute; Hemostatic Disorders

Condition Hierarchy (Ancestors)

Leukemia, Myeloid, Acute; Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Vascular Diseases; Cardiovascular Diseases; Hemorrhagic Disorders

Study Officials

• Jin Zhou, MD, PhD

  First Affiliated Hospital of Harbin Medical University

  STUDY CHAIR

Central Study Contacts

Jin Zhou, MD, PhD

CONTACT

008645185555951; zhoujin1111@126.com

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 2, 2016
• First Posted: December 13, 2016
• Study Start: October 1, 2014
• Primary Completion: December 1, 2019
• Study Completion: December 1, 2020
• Last Updated: April 24, 2018

Record last verified: 2018-04

Data Sharing

• IPD Sharing: Will share

Locations

CN (1)