Thrombotic potential during pediatric acute lymphoblastic leukemia induction: Role of cell-free DNA.
cell‐free nucleic acids
child
extracellular traps
induction chemotherapy
leukemia
thrombin generation
Journal
Research and practice in thrombosis and haemostasis
ISSN: 2475-0379
Titre abrégé: Res Pract Thromb Haemost
Pays: United States
ID NLM: 101703775
Informations de publication
Date de publication:
Jul 2021
Jul 2021
Historique:
received:
29
04
2021
accepted:
18
05
2021
entrez:
2
8
2021
pubmed:
3
8
2021
medline:
3
8
2021
Statut:
epublish
Résumé
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. We aimed to show that extracellular traps and cell-free DNA (cfDNA) promote thrombin generation in pediatric ALL. 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. 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. 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.
Sections du résumé
BACKGROUND
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
OBJECTIVE
We aimed to show that extracellular traps and cell-free DNA (cfDNA) promote thrombin generation in pediatric ALL.
METHODS
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
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
CONCLUSIONS
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.
Identifiants
pubmed: 34337307
doi: 10.1002/rth2.12557
pii: S2475-0379(22)01418-2
pmc: PMC8312738
doi:
Types de publication
Journal Article
Langues
eng
Pagination
e12557Subventions
Organisme : CSRD VA
ID : I01 CX001932
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG049784
Pays : United States
Informations de copyright
© 2021 The Authors. Research and Practice in Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis (ISTH).
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