Journal article
Thrombotic potential during pediatric acute lymphoblastic leukemia induction: Role of cell‐free DNA
Research and practice in thrombosis and haemostasis, Vol.5(5), pp.e12557-n/a
07/2021
DOI: 10.1002/rth2.12557
PMCID: PMC8312738
PMID: 34337307
Abstract
Background
Thromboembolism affects up to 30% of children undergoing treatment for acute lymphoblastic leukemia (ALL). Increased thrombin generation has been reported in ALL, but the mechanisms remain elusive.
Objective
We aimed to show that extracellular traps and cell‐free DNA (cfDNA) promote thrombin generation in pediatric ALL.
Methods
In a longitudinal single‐center study, we recruited 17 consecutive pediatric ALL patients. Serial blood samples were collected at diagnosis and weekly during the 4‐week induction phase of antileukemic chemotherapy. Healthy children (n = 14) and children with deep vein thrombosis (DVT; n = 7) or sepsis (n = 5) were recruited as negative and positive controls, respectively. In plasma, we measured endogenous thrombin generation potential (ETP) and components of extracellular traps, including cfDNA.
Results
In patients with ALL, ETP was increased at baseline and remained significantly elevated throughout the induction therapy. Plasma levels of cfDNA were increased at baseline and during the first 3 weeks of induction therapy. The extent of enhancement of ETP and plasma cfDNA in patients with ALL was similar to that seen in patients with DVT or sepsis. Treatment of plasma with DNase 1 lowered ETP in patients with ALL at each time point but did not affect ETP in healthy controls.
Conclusion
We conclude that childhood ALL is associated with a prothrombotic milieu at the time of diagnosis that continues during induction chemotherapy, and cfDNA contributes to increased thrombogenic potential.
Details
- Title: Subtitle
- Thrombotic potential during pediatric acute lymphoblastic leukemia induction: Role of cell‐free DNA
- Creators
- Rahul Kumar - University of IowaParmeshwar B. Katare - University of IowaSteven R. Lentz - University of IowaArunkumar J. Modi - University of IowaAnjali A. Sharathkumar - University of IowaSanjana Dayal - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Research and practice in thrombosis and haemostasis, Vol.5(5), pp.e12557-n/a
- DOI
- 10.1002/rth2.12557
- PMID
- 34337307
- PMCID
- PMC8312738
- ISSN
- 2475-0379
- eISSN
- 2475-0379
- Number of pages
- 8
- Grant note
- American Heart Association (18IPA34180014; 19POST34380100) National Institute of Health (AG049784) University of Iowa pilot Dance Marathon award U.S. Department of Veterans Affairs (I01 CX001932)
- Language
- English
- Date published
- 07/2021
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Hematology/Oncology; Fraternal Order of Eagles Diabetes Research Center; Internal Medicine
- Record Identifier
- 9984353844402771
Metrics
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