OC 64.3 - Biomarkers of bleeding and venous thromboembolism in patients with acute leukemia

Tuesday, June 27, 2023

15:15 – 15:30 ET

Room: 511

Session Available As: On-Demand

Presenting Author(s)

Yohei Hisada, PhD

Assistant Professor
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, United States

Co-Author(s)

SA

Sierra J. Archibald

Research Technician
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, United States
KB

Karan Bansal

Clinical research coordinator
University of Alabama at Birmingham
Birmingham, Alabama, United States
YC

Yanjun Chen

Statistician
University of Alabama at Birmingham
Birmingham, Alabama, United States
SD

Sindhu Dwarampudi

Undergraduate student
University of Alabama at Birmingham
Birmingham, Alabama, United States
NB

Nora Balas

Clinical data analyst
University of Alabama at Birmingham
Birmingham, Alabama, United States
LH

Lindsey Hageman

Research Manager
University of Alabama at Birmingham
Birmingham, Alabama, United States
AM

Amanda Mullen

Researcher
University of Alabama at Birmingham
Birmingham, Alabama, United States
NK

Nigel S. Key

Harold R. Roberts Distinguished Professor
Division of Hematology, University of North Carolina, Chapel Hill, NC, USA
Chapel Hill, North Carolina, United States
SB

Smita Bhatia

Professor
University of Alabama at Birmingham
Birmingham, Alabama, United States
RB

Ravi Bhatia

Professor
University of Alabama at Birmingham
Birmingham, Alabama, United States
Nigel Mackman, PhD

Professor
Univerisity of North Carolina at Chapel Hill
Chapel Hill, North Carolina, United States
RG

Radhika Gangaraju

Assistant Professor
University of Alabama at Birmingham
Birmingham, Alabama, United States

Background: Coagulopathy with associated bleeding and venous thromboembolism (VTE) is a major cause of early morbidity and mortality in patients with acute leukemia. However, the mechanisms leading to bleeding and VTE have not been fully elucidated.

Aims: Compare levels of plasma biomarkers in the coagulation and fibrinolytic pathways and, neutrophil extracellular trap formation in adult patients with acute promyelocytic leukemia (APL), acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) with a healthy control population. Evaluate the associations between biomarker levels and bleeding and VTE in acute leukemia patients.

Methods: Plasma samples were obtained from 29 APL, 253 AML, and 76 ALL patients and clinical data were abstracted medical records. Plasma was obtained from 30 age-, sex-, and race-matched-healthy individuals. Extracellular vesicle (EV) tissue factor (TF) activity and citrullinated histone H3-DNA complex were measured using in-house assays. Phosphatidylserine-positive EVs, cell-free DNA, plasmin-antiplasmin complex, tissue plasminogen activator (tPA) and active plasminogen activator inhibitor-1 (PAI-1) were measured using commercial assays. The association between biomarkers and bleeding/VTE was examined using proportional sub-distribution hazards regression analysis. Biomarkers were considered as tertiles and adjusted for age, sex, and race. Sub-analyses were performed for AML patients.

Results: APL patients had the highest levels of EVTF activity. ALL patients had the highest levels of cell-free DNA. Increased EVTF activity (HR 2.33, 95%CI: 1.08-5.04, p=0.03) was associated with bleeding in all leukemia patients, and in AML patients (HR 2.73, 95%CI: 1.04-7.17, p=0.04). Increased active PAI-1 level was associated with VTE in all leukemia patients (HR 3.40, 95%CI: 1.33-8.70, p=0.01) and in AML patients (HR 3.61, 95%CI: 1.05-12.35, p=0.04). We found that tPA level (HR 0.50, 95%CI: 0.25-0.98, p=0.04) was associated with lower VTE risk in all leukemia patients.

Conclusion(s): Measurement of EVTF activity and active PAI-1 may help to identify acute leukemia patients at high risk of bleeding and VTE, respectively.

Learning Objectives:

Upon completion, participants will be able to understand the differences of levels of biomarkers of coagulation and fibrinolysis in different types of acute leukemia.
Upon completion, participants will be able to understand extracellular vescile tissue factor activity is associated with bleeding in acute leukemia patients.
Upon completion, participants will be able to understand levels of plasminogen activator inhibitor-1 are associated with venous thromboembolism in acute leukemia patients.