Thrombotic potential during pediatric acute lymphoblastic leukemia induction: Role of cell‐free DNA
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) prom...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2021-07-01
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| Series: | Research and Practice in Thrombosis and Haemostasis |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/rth2.12557 |
| _version_ | 1797721985739915264 |
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| author | Rahul Kumar Parmeshwar B. Katare Steven R. Lentz Arunkumar J. Modi Anjali A. Sharathkumar Sanjana Dayal |
| author_facet | Rahul Kumar Parmeshwar B. Katare Steven R. Lentz Arunkumar J. Modi Anjali A. Sharathkumar Sanjana Dayal |
| author_sort | Rahul Kumar |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-12T09:41:14Z |
| format | Article |
| id | doaj.art-6636d3a8a7b6416bae4889ff22585964 |
| institution | Directory Open Access Journal |
| issn | 2475-0379 |
| language | English |
| last_indexed | 2024-03-12T09:41:14Z |
| publishDate | 2021-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Research and Practice in Thrombosis and Haemostasis |
| spelling | doaj.art-6636d3a8a7b6416bae4889ff225859642023-09-02T13:13:46ZengElsevierResearch and Practice in Thrombosis and Haemostasis2475-03792021-07-0155n/an/a10.1002/rth2.12557Thrombotic potential during pediatric acute lymphoblastic leukemia induction: Role of cell‐free DNARahul Kumar0Parmeshwar B. Katare1Steven R. Lentz2Arunkumar J. Modi3Anjali A. Sharathkumar4Sanjana Dayal5Department of Internal Medicine University of Iowa Iowa City IA USADepartment of Internal Medicine University of Iowa Iowa City IA USADepartment of Internal Medicine University of Iowa Iowa City IA USADepartment of Pediatrics University of Iowa Iowa City IA USADepartment of Pediatrics University of Iowa Iowa City IA USADepartment of Internal Medicine University of Iowa Iowa City IA USAAbstract 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.https://doi.org/10.1002/rth2.12557cell‐free nucleic acidschildextracellular trapsinduction chemotherapyleukemiathrombin generation |
| spellingShingle | Rahul Kumar Parmeshwar B. Katare Steven R. Lentz Arunkumar J. Modi Anjali A. Sharathkumar Sanjana Dayal Thrombotic potential during pediatric acute lymphoblastic leukemia induction: Role of cell‐free DNA Research and Practice in Thrombosis and Haemostasis cell‐free nucleic acids child extracellular traps induction chemotherapy leukemia thrombin generation |
| title | Thrombotic potential during pediatric acute lymphoblastic leukemia induction: Role of cell‐free DNA |
| title_full | Thrombotic potential during pediatric acute lymphoblastic leukemia induction: Role of cell‐free DNA |
| title_fullStr | Thrombotic potential during pediatric acute lymphoblastic leukemia induction: Role of cell‐free DNA |
| title_full_unstemmed | Thrombotic potential during pediatric acute lymphoblastic leukemia induction: Role of cell‐free DNA |
| title_short | Thrombotic potential during pediatric acute lymphoblastic leukemia induction: Role of cell‐free DNA |
| title_sort | thrombotic potential during pediatric acute lymphoblastic leukemia induction role of cell free dna |
| topic | cell‐free nucleic acids child extracellular traps induction chemotherapy leukemia thrombin generation |
| url | https://doi.org/10.1002/rth2.12557 |
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