Journal article
Endothelial dysfunction and thromboembolism in children, adolescents, and young adults with acute lymphoblastic leukemia
University of Copenhagen1
Landspitali University Hospital2
Aarhus University3
Bioinformatics, Department of Health Technology, Technical University of Denmark4
Disease Data Intelligence, Bioinformatics, Department of Health Technology, Technical University of Denmark5
Department of Health Technology, Technical University of Denmark6
Oslo University Hospital7
St. Olav's University Hospital8
Vilnius University Hospital Santaros Klinikos9
Tallinn Children’s Hospital10
...and 0 moreEndothelial dysfunction has not previously been investigated as a thrombogenic risk factor among patients with acute lymphoblastic leukemia (ALL), known to be at high risk of thromboembolism. We retrospectively explored the association between three circulating biomarkers of endothelial dysfunction (thrombomodulin, syndecan-1, VEGFR-1) measured in prospectively collected blood samples and risk of thromboembolism in 55 cases and 165 time-matched controls, treated according to the NOPHO ALL2008 protocol.
In age-, sex-, and risk group-adjusted analysis, increasing levels of thrombomodulin and VEGFR-1 were independently associated with increased odds of developing thromboembolism (OR 1.37 per 1 ng/mL [95% CI 1.20‒1.56, P < 0.0001] and OR 1.21 per 100 pg/mL [95% CI 1.02‒1.21, P = 0.005], respectively).
These associations remained significant when including only samples drawn >30 days before thromboembolic diagnosis. Thrombomodulin levels were on average 3.2 ng/mL (95% CI 2.6–8.2 ng/mL) higher in samples with measurable asparaginase activity (P < 0.0001). Among single nucleotide variants located in or neighboring coding genes for the three biomarkers, none were significantly associated with odds of thromboembolism.
If results are validated in another cohort, thrombomodulin and VEGFR-1 could serve as predictive biomarkers, identifying patients in need of preemptive antithrombotic prophylaxis.
Language: | English |
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Publisher: | Nature Publishing Group UK |
Year: | 2022 |
Pages: | 361-369 |
ISSN: | 14765551 and 08876924 |
Types: | Journal article |
DOI: | 10.1038/s41375-021-01383-2 |
ORCIDs: | 0000-0003-3437-8338 , 0000-0003-0578-3887 , Linnemann Nielsen, Rikke , 0000-0002-8584-5920 , 0000-0002-8996-1195 , 0000-0002-0829-4993 , 0000-0002-3902-3694 and 0000-0001-6398-6979 |
Adolescent Adult Asparaginase Case-Control Studies Child Child, Preschool DISSEMINATED INTRAVASCULAR COAGULATION Endothelium, Vascular Female Follow-Up Studies GROWTH-FACTOR Humans Infant L-ASPARAGINASE Male Middle Aged POSTTHROMBOTIC SYNDROME PROTEIN-C Precursor Cell Lymphoblastic Leukemia-Lymphoma Prognosis RISK Retrospective Studies Risk Factors THROMBIN GENERATION THROMBOMODULIN LEVEL TNF-ALPHA Thromboembolism VON-WILLEBRAND-FACTOR Young Adult