Thrombophilia gene mutations predict venous thromboembolism in ambulatory cancer patients receiving chemotherapy.


Journal

Journal of thrombosis and haemostasis : JTH
ISSN: 1538-7836
Titre abrégé: J Thromb Haemost
Pays: England
ID NLM: 101170508

Informations de publication

Date de publication:
11 2023
Historique:
received: 16 05 2023
revised: 17 07 2023
accepted: 21 07 2023
medline: 23 10 2023
pubmed: 4 8 2023
entrez: 3 8 2023
Statut: ppublish

Résumé

Inherited thrombophilia and cancer both independently increase the risk of venous thromboembolism (VTE). However, whether the increased VTE risk associated with inherited thrombophilia exists in cancer patients is less clear. Our objective was to determine the influence of inherited thrombophilia on VTE and bleeding risk in moderate-to-high-risk ambulatory cancer patients receiving chemotherapy. We conducted a post hoc analysis using blood samples from patients enrolled in the AVERT trial to determine if previously recognized thrombophilia gene mutations (prothrombin factor [F] II G20210A, FXI, fibrinogen gamma, serpin family A member 10, FV K858R, FXIII, FV Leiden [FVL], and ABO blood) were associated with VTE or bleeding during the 7-months after starting chemotherapy. Logistic regression was used to compare heterozygous and homozygous mutations (combined) to wild-type. VTE rates, bleeding rates, and risk differences for mutations stratified by prophylactic anticoagulation use were calculated. Of the 447 patients, there were 39 VTE and 39 bleeding events. The odds of VTE were significantly increased with FVL mutation and non-O blood type (odds ratio [OR]: 5.2; 95% CI: 1.9-14.7 and OR: 2.7; 95% CI: 1.2-6.1, respectively). The use of anticoagulation prophylaxis resulted in complete protection in FVL patients, whereas those not receiving anticoagulation had a VTE rate of 119 per 100 patient-years. Lower VTE rates were also observed in non-O blood type patients taking prophylactic anticoagulation. No other thrombophilia genes tested were significantly associated with VTE or bleeding. Our results indicate that FVL mutation and ABO blood type may be important VTE predictors in cancer patients starting chemotherapy.

Sections du résumé

BACKGROUND
Inherited thrombophilia and cancer both independently increase the risk of venous thromboembolism (VTE). However, whether the increased VTE risk associated with inherited thrombophilia exists in cancer patients is less clear.
OBJECTIVES
Our objective was to determine the influence of inherited thrombophilia on VTE and bleeding risk in moderate-to-high-risk ambulatory cancer patients receiving chemotherapy.
METHODS
We conducted a post hoc analysis using blood samples from patients enrolled in the AVERT trial to determine if previously recognized thrombophilia gene mutations (prothrombin factor [F] II G20210A, FXI, fibrinogen gamma, serpin family A member 10, FV K858R, FXIII, FV Leiden [FVL], and ABO blood) were associated with VTE or bleeding during the 7-months after starting chemotherapy. Logistic regression was used to compare heterozygous and homozygous mutations (combined) to wild-type. VTE rates, bleeding rates, and risk differences for mutations stratified by prophylactic anticoagulation use were calculated.
RESULTS
Of the 447 patients, there were 39 VTE and 39 bleeding events. The odds of VTE were significantly increased with FVL mutation and non-O blood type (odds ratio [OR]: 5.2; 95% CI: 1.9-14.7 and OR: 2.7; 95% CI: 1.2-6.1, respectively). The use of anticoagulation prophylaxis resulted in complete protection in FVL patients, whereas those not receiving anticoagulation had a VTE rate of 119 per 100 patient-years. Lower VTE rates were also observed in non-O blood type patients taking prophylactic anticoagulation. No other thrombophilia genes tested were significantly associated with VTE or bleeding.
CONCLUSION
Our results indicate that FVL mutation and ABO blood type may be important VTE predictors in cancer patients starting chemotherapy.

Identifiants

pubmed: 37536569
pii: S1538-7836(23)00580-9
doi: 10.1016/j.jtha.2023.07.017
pii:
doi:

Substances chimiques

Factor V 9001-24-5
Prothrombin 9001-26-7
Anticoagulants 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

3184-3192

Subventions

Organisme : CIHR
Pays : Canada

Informations de copyright

Copyright © 2023 International Society on Thrombosis and Haemostasis. Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of competing interests T.-F.W. reports advisory board honoraria from Servier and Valeo and research funding from Leo Pharma. M.C. reports grants from BMS, Leo Pharma, and Pfizer and honoraria from BMS, Leo Pharma, Bayer, Pfizer, Servier, and Sanofi. D.R., R.M., D.B., S.H., and P.S.W. have no conflicts of interest to declare.

Auteurs

Danielle Carole Roy (DC)

School of Epidemiology and Public Health, University of Ottawa, Ottawa, Ontario, Canada. Electronic address: droy058@uottawa.ca.

Tzu-Fei Wang (TF)

School of Epidemiology and Public Health, University of Ottawa, Ottawa, Ontario, Canada; Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada; The Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.

Marc Carrier (M)

School of Epidemiology and Public Health, University of Ottawa, Ottawa, Ontario, Canada; Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada; The Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.

Ranjeeta Mallick (R)

School of Epidemiology and Public Health, University of Ottawa, Ottawa, Ontario, Canada; Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada; The Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.

Dylan Burger (D)

Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada; The Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.

Steven Hawken (S)

School of Epidemiology and Public Health, University of Ottawa, Ottawa, Ontario, Canada; The Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.

Philip S Wells (PS)

School of Epidemiology and Public Health, University of Ottawa, Ottawa, Ontario, Canada; Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada; The Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.

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