The role of coagulation factors VIII, IX and XI in the prediction and mediation of recurrent thrombotic events in children with non-central venous catheter deep vein thrombosis

Alessandra Bosch; Kirsten Brunsvig Jarvis; Leonardo R Brandão; Yushu Zou; Jennifer Vincelli; Nour Amiri; Laura Avila

doi:10.1016/j.thromres.2024.03.009

The role of coagulation factors VIII, IX and XI in the prediction and mediation of recurrent thrombotic events in children with non-central venous catheter deep vein thrombosis

Thromb Res. 2024 Apr:236:228-235. doi: 10.1016/j.thromres.2024.03.009. Epub 2024 Mar 7.

Authors

Alessandra Bosch¹, Kirsten Brunsvig Jarvis², Leonardo R Brandão³, Yushu Zou⁴, Jennifer Vincelli⁵, Nour Amiri⁵, Laura Avila³

Affiliations

¹ Division of Haematology/Oncology, The Hospital for Sick Children, Toronto, Ontario, Canada; University Children's Hospital Zurich, Department of Haematology, Zurich, Switzerland. Electronic address: Alessandra.bosch@kispi.uzh.ch.
² Division of Haematology/Oncology, The Hospital for Sick Children, Toronto, Ontario, Canada; Oslo University Hospital, Department of Pediatric Hematology and Oncology, Oslo, Norway.
³ Division of Haematology/Oncology, The Hospital for Sick Children, Toronto, Ontario, Canada; Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada; Child Health Evaluative Sciences, Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada.
⁴ Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.
⁵ Division of Haematology/Oncology, The Hospital for Sick Children, Toronto, Ontario, Canada.

PMID: 38484629
DOI: 10.1016/j.thromres.2024.03.009

Abstract

Background: The role of elevated coagulation factors VIII (FVIII), FIX, FXI for the prediction of recurrent thrombotic events in children after an index non-central venous catheter (non-CVC) related deep vein thrombosis (DVT) remains unclear.

Objective: This study investigates the predictive role of FVIII, FIX, and FXI for recurrent thrombosis in children with index non-CVC DVTs, and the mediation effect of FVIII on chronic inflammation and recurrent thrombosis.

Methods: Children aged 0-18 years diagnosed with an index non-CVC related DVT (1993-2020) were included in this single-center retrospective cohort study. Plasma levels of FVIII, FIX, FXI were measured cross-sectionally ≥30 days after the acute DVT. The association between the continuous variables FVIII, FIX, FXI and thrombosis recurrence was investigated using uni- and multivariable logistic regression, adjusting for age, sex, and chronic inflammation. Mediation analysis assessed the role of FVIII as a mediator between chronic inflammation and recurrent thrombosis. Ethics approval was obtained.

Results: A total of 139 children with an index non-CVC related DVT were included. Thirty-eight (27 %) had a recurrent thrombosis at a median of 237 days (P25-P75 65-657 days) after the index DVT. In uni- and multivariable-analysis, FVIII, FIX or FXI did not predict thrombosis recurrence; However, chronic inflammation was an independent predictor. There was no evidence that FVIII mediated the effect of chronic inflammation on thrombosis recurrence.

Conclusion: We found no evidence that elevated FVIII, FIX or FXI predicted thrombosis recurrence, or evidence of a mediating role of FVIII. Underlying chronic inflammation predicted venous recurrent thrombotic events in this cohort.

Keywords: Blood coagulation factors; Inflammation; Mediation analysis; Pediatrics; Recurrence; Venous thromboembolism.

MeSH terms

Catheters
Child
Hemostatics*
Humans
Inflammation
Retrospective Studies
Risk Factors
Thrombosis* / etiology
Venous Thrombosis* / diagnosis

Substances

Hemostatics