Biomarkers of bleeding and venous thromboembolism in patients with acute leukemia

Yohei Hisada; Sierra J Archibald; Karan Bansal; Yanjun Chen; Chen Dai; Sindhu Dwarampudi; Nora Balas; Lindsey Hageman; Nigel S Key; Smita Bhatia; Ravi Bhatia; Nigel Mackman; Radhika Gangaraju

doi:10.1016/j.jtha.2024.03.020

Biomarkers of bleeding and venous thromboembolism in patients with acute leukemia

J Thromb Haemost. 2024 Apr 2:S1538-7836(24)00178-8. doi: 10.1016/j.jtha.2024.03.020. Online ahead of print.

Authors

Affiliations

¹ UNC Blood Research Center, Division of Hematology, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA. Electronic address: yohei_hisada@med.unc.edu.
² UNC Blood Research Center, Division of Hematology, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
³ Institute for Cancer Outcomes and Survivorship, School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.
⁴ Department of Medicine, School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.
⁵ Institute for Cancer Outcomes and Survivorship, School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA; Department of Medicine, School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA. Electronic address: rgangaraju@uabmc.edu.

PMID: 38574862
DOI: 10.1016/j.jtha.2024.03.020

Abstract

Background: Coagulopathy and associated bleeding and deep vein thrombosis (DVT) are major causes of morbidity and mortality in patients with acute leukemia. The underlying mechanisms of these complications have not been fully elucidated.

Objectives: To evaluate the associations between biomarker levels and bleeding and DVT in acute leukemia patients.

Methods: We examined plasma levels of activators, inhibitors, and biomarkers of the coagulation and fibrinolytic pathways in patients aged ≥18 years with newly diagnosed acute leukemia compared with those of normal controls. Multivariable regression models were used to examine the association of biomarkers with bleeding and DVT in acute leukemia patients. The study included 358 patients with acute leukemia (29 with acute promyelocytic leukemia [APL], 253 with non-APL acute myeloid leukemia, and 76 with acute lymphoblastic leukemia) and 30 normal controls.

Results: Patients with acute leukemia had higher levels of extracellular vesicle tissue factor (EVTF) activity, phosphatidylserine-positive extracellular vesicles, plasminogen activator inhibitor-1, plasmin-antiplasmin complexes, and cell-free DNA and lower levels of citrullinated histone H3-DNA complexes compared with normal controls. APL patients had the highest levels of EVTF activity and the lowest levels of tissue plasminogen activator among acute leukemia patients. There were 41 bleeding and 23 DVT events in acute leukemia patients. High EVTF activity was associated with increased risk of bleeding (subdistribution hazard ratio, 2.30; 95% CI, 0.99-5.31), whereas high levels of plasminogen activator inhibitor-1 were associated with increased risk of DVT (subdistribution hazard ratio, 3.00; 95% CI, 0.95-9.47) in these patients.

Conclusion: Our study shows alterations in several biomarkers in acute leukemia and identifies biomarkers associated with risk of bleeding and DVT.

Keywords: acute leukemia; biomarker; bleeding; deep vein thrombosis; disseminated intravascular coagulation.