Secondary prophylaxis of venous thromboembolism (VTE) with low dose apixaban or rivaroxaban in major-thrombophilia carriers.
Bleeding adverse events
Direct oral anticoagulants (DOACs)
Low-dose DOACs
VTE recurrence
Venous thromboembolism secondary prophylaxis
Journal
Annals of hematology
ISSN: 1432-0584
Titre abrégé: Ann Hematol
Pays: Germany
ID NLM: 9107334
Informations de publication
Date de publication:
08 Oct 2024
08 Oct 2024
Historique:
received:
15
02
2024
accepted:
19
09
2024
medline:
9
10
2024
pubmed:
9
10
2024
entrez:
8
10
2024
Statut:
aheadofprint
Résumé
Direct oral anticoagulants (DOACs) are widely used for treatment and secondary prophylaxis of venous thromboembolism (VTE) and represent the gold standard for VTE secondary prophylaxis, with low-intensity DOACs administration becoming increasingly used worldwide in such scenario. Albeit widespread DOACs usage there are few literature data regarding their efficacy and safety in major thrombophilia carriers and almost no data is available for low intensity apixaban and rivaroxaban as secondary VTE prophylaxis in such patients. The aim of our study is to evaluate and confront the efficacy and safety of low-dose DOACs for VTE secondary prophylaxis, in major thrombophilia carriers vs patients at high risk of VTE recurrence for other reasons. We retrospectively evaluated patients who required long-term anticoagulant secondary prophylaxis to prevent recurrent VTE, treated with apixaban 2.5 mg BID or rivaroxaban 10 mg daily and that were screened for thrombophilia. The examined patients were 339. Baseline characteristics such as sex, age, obesity rate, smoking, number of previous VTEs and comorbidities (such as cardiovascular diseases, diabetes, mild CKD) were equally distributed in either group. The median low-dose DOACs administration time was 19.20 months (IQR 12.17-35.67). During low-dose DOACs treatment, 13 (3.8%) VTE recurrences were observed; 14 bleeding events were registered (4,1%), with no major bleeding (MB), 6 clinically relevant non major bleeding (CRNMB) (1.8%) and 8 minor bleeding (2.3%). No statistically significant difference in the rate of VTE recurrence and/or bleeding events emerged between major thrombophilia carriers and non-major thrombophilia carriers. In multivariate analysis increased risk of VTE recurrence was found for patients with cardiovascular comorbidities (HR 4.00 - p = 0.034) and for patients with more than one previous VTE episode (HR 5.14 - p = 0.034). Our data suggest that low-dose DOACs may be effective and safe in secondary VTE prophylaxis for carriers of major thrombophilia with no increase in VTE recurrence and/or bleeding risk.
Identifiants
pubmed: 39379551
doi: 10.1007/s00277-024-06021-2
pii: 10.1007/s00277-024-06021-2
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
Références
Rosendaal FR (1999) Venous thrombosis: a multicausal disease. The Lancet 353(9159):1167–1173
doi: 10.1016/S0140-6736(98)10266-0
Couturaud F, Leroyer C, Julian JA et al (2009) Factors that predict risk of thrombosis in relatives of patients with unprovoked venous thromboembolism. Chest J 136(6):1537–1545
doi: 10.1378/chest.09-0757
Christiansen SC, Cannegieter SC, Koster T, Vandenbroucke JP, Rosendaal FR (2005) Thrombophilia, clinical factors, and recurrent venous thrombotic events. JAMA 293:2352–2361
doi: 10.1001/jama.293.19.2352
Klemen ND, Feingold PL, Hashimoto B, Wang M, Kleyman S, Brackett A, Gross CP, Pei KY (2020) Mortality risk associated with venous thromboembolism: a systematic review and Bayesian meta-analysis. Lancet Haematol 7:e583–e593
doi: 10.1016/S2352-3026(20)30211-8
Cushman M (2007) Epidemiology and risk factors for venous thrombosis. Semin Hematol 44(2):62–69
doi: 10.1053/j.seminhematol.2007.02.004
Garcia-Horton A, Kovacs MJ, Abdulrehman J, Taylor JE, Sharma S, Lazo-Langner A (2017) Impact of thrombophilia screening on venous thromboembolism management practices. Thromb Res 149:76–80
doi: 10.1016/j.thromres.2016.11.023
Lijfering WM, Brouwer JL, Veeger NJ, Bank I, Coppens M, Middeldorp S, Hamulyak K, Prins MH, Buller HR, van der Meer J (2009) Selective testing for thrombophilia in patients with first venous thrombosis: results from a retrospective family cohort study on absolute thrombotic risk for currently known thrombophilic defects in 2479 relatives. Blood 113:5314–5322
doi: 10.1182/blood-2008-10-184879
Crowther MA, Kelton JG (2003) Congenital thrombophilic states associated with venous thrombosis: a qualitative overview and proposed classification system. Ann Intern Med 138:128–134
doi: 10.7326/0003-4819-138-2-200301210-00014
Ortel TL, Neumann I, Ageno W et al (2020) American Society of Hematology 2020 guidelines for management of venous thromboembolism: treatment of deep vein thrombosis and pulmonary embolism. Blood Adv 4(19):4693–4738
doi: 10.1182/bloodadvances.2020001830
Agnelli G, Buller HR, Cohen A, AMPLIFY-EXT Investigators et al (2013) Apixaban for extended treatment of venous thromboembolism. N Engl J Med. 368(8):699–708
doi: 10.1056/NEJMoa1207541
Weitz JI, Lensing AWA, Prins MH, EINSTEIN CHOICE Investigators et al (2017) Rivaroxaban or aspirin for extended treatment of venous thromboembolism. N Engl J Med. 376(13):1211–1222
doi: 10.1056/NEJMoa1700518
Ho WK, Hankey GJ, Quinlan DJ, Eikelboom JW (2006) Risk of recurrent venous thromboembolism in patients with common thrombophilia: A systematic review. Arch Intern Med 166:729–736
doi: 10.1001/archinte.166.7.729
Segal JB, Brotman DJ, Necochea AJ, Emadi A, Samal L, Wilson LM, Crim MT (2009) Bass EB Predictive value of factor V Leiden and prothrombin G20210A in adults with venous thromboembolism and in family members of those with a mutation: A systematic review. JAMA 301:2472–2485
doi: 10.1001/jama.2009.853
Connors JM (2017) Thrombophilia Testing and Venous Thrombosis. N Engl J Med 377(12):1177–1187
doi: 10.1056/NEJMra1700365
Middeldorp S, Nieuwlaat R, Baumann Kreuziger L, Coppens M, Houghton D, James AH, Lang E, Moll S, Myers T, Bhatt M, Chai-Adisaksopha C, Colunga-Lozano LE, Karam SG, Zhang Y, Wiercioch W, Schünemann HJ, Iorio A (2023) American Society of Hematology 2023 guidelines for management of venous thromboembolism: thrombophilia testing. Blood Adv 7(22):7101–7138
doi: 10.1182/bloodadvances.2023010177
Stevens SM, Woller SC, Kreuziger LB, Bounameaux H, Doerschug K, Geersing GJ, Huisman MV, Kearon C, King CS, Knighton AJ, Lake E, Murin S, Vintch JRE, Wells PS, Moores LK (2021) Antithrombotic Therapy for VTE Disease: Second Update of the CHEST Guideline and Expert Panel Report. Chest 160(6):e545–e608
doi: 10.1016/j.chest.2021.07.055
Yagi S, Kagawa K, Fujimoto E, Sata M (2019) Recurrent venous thrombosis during direct oral anticoagulant therapy in a patient with protein S deficiency. J Med Investig JMI 66:182–184
doi: 10.2152/jmi.66.182
Lou J, Yin L, Ke X, Zhang L, Xu F, Liu Z (2020) A case-report of two patients with hereditary protein s deficiency treated by Rivaroxaban. Blood Coagul Fibrinolysis Int J Haemost Thromb. 31:405–409
doi: 10.1097/MBC.0000000000000929
Tripodi A, Martinelli I, Chantarangkul V, Clerici M, Artoni A, Passamonti S, Peyvandi F (2016) Thrombin Generation and other coagulation parameters in a patient with homozygous congenital protein S deficiency on treatment with Rivaroxaban. Int J Hematol 103:165–172
doi: 10.1007/s12185-015-1898-6
Nojima Y, Ihara M, Adachi H, Kurimoto T, Nanto S (2019) Efficacy and safety of apixaban in a patient with systemic venous thromboembolism associated with hereditary antithrombin deficiency. J Cardiol Cases 19:106–109
doi: 10.1016/j.jccase.2018.12.007
Cook RM, Rondina MT, Horton DJ (2014) Rivaroxaban for the long-term treatment of spontaneous ovarian vein thrombosis caused by factor V leiden homozygosity. Ann Pharmacother 48:1055–1060
doi: 10.1177/1060028014533304
Costa RL, Triggs M, Cole SE, Lacey J, Reddy S (2020) Anticoagulation therapy in a patient with heterozygous factor V Leiden and coexisting homozygous prothrombin gene mutations. Cureus 12:e11949
Campello E, Spiezia L, Simion C, Tormene D, Camporese G, Dalla Valle F, Poretto A, Bulato C, Gavasso S, Radu CM et al (2020) Direct oral anticoagulants in patients with inherited thrombophilia and venous thromboembolism: a prospective cohort study. J Am Heart Assoc 9:e018917
doi: 10.1161/JAHA.120.018917
Serrao A, Lucani B, Mansour D, Ferretti A, Baldacci E, Santoro C, Foà R, Chistolini A (2019) Direct oral anticoagulants in patients affected by major congenital thrombophilia. Mediterr J Hematol Infect Dis 11(1):e2019044
doi: 10.4084/mjhid.2019.044
Serrao A, Assanto GM, Mormile R, Brescini M, Santoro C, Chistolini A (2022) Secondary prophylaxis of venous thromboembolism with direct oral anticoagulants: comparison between patients with major congenital thrombophilia versus non-thrombophilic patients. Intern Emerg Med 17(4):1081–1085
doi: 10.1007/s11739-021-02917-3
Laganà A, Assanto GM, Masucci C et al (2024) Secondary prophylaxis of venous thromboembolism (VTE) with low dose apixaban or rivaroxaban: results from a patient population with more than 2 years of median follow-up. Mediterr J Hematol Infect Dis. 16(1):e2024020
doi: 10.4084/MJHID.2024.020