The Influence of Thrombophilic Gene Mutation on Recurrence of Venous Thromboembolism: A Retrospective Cross-Sectional Study

Yıl 2019, Cilt: 41 Sayı: 1, 72 - 80, 01.01.2019

Emrah Şişli , Öztekin Oto

https://doi.org/10.20515/otd.435819

Cited By: 1

Öz

The aim of this study is to evaluate the influence of the risk factors
from the point of thrombophilic gene mutations (TGM) with type and inter-cooperation’s
on recurrence in venous thromboembolism (VTE) patients.This retrospectively and
cross-sectionally designed study was conducted between 2008–2009. The VTE
patients, who were evaluated for TGM were elected. Among a total of 109
patients, the mean age at first VTE event was 42.6±14.1 years. Fifty-nine
(54.1%) patients were male. While 33 (30.3%) patients had primary VTE, 46
(42.2%) patients had recurrent VTE (rVTE). In the univariate analysis, the
significant variables associated with the increased rate of rVTE were age ≥40
years, first event at in-hospital, malignancy, internal medical disease, TGM,
factor V Leiden, prothrombin G20210A. The analyses of different mutation count
on rVTE pointed that, there were significant differences in recurrence rates,
except groups with no mutation and one mutation. Additionally, with the
increasing number of clinical risk factors and TGM per case were considerably
associated with rVTE in both univariate and multivariate analysis. Regarding
the risk of rVTE, the TGMs were significant but do not appear to play a vital
role per se. However, simultaneous existence of clinical risk factors,
including TGM seem to be more important for the prediction of rVTE.

Anahtar Kelimeler

Venous thromboembolism, Recurrence, Factor V Leiden, Prothrombin G20210A, Methylenetetrahydrofolate reductase C677T, Methylenetetrahydrofolate reductase A1298C

Tekrarlayan Venöz Tromboemboli’ye Trombofilik Gen Mutasyonunun Etkisi: Geriye-Dönük Kesitsel Bir Araştırma

Öz

Bu çalışmanın amacı, trombofilik gene mutasyonu (TGM) tipi ve
birlikteliği açısından tekrarlayan venöz tromboemboli (rVTE) hastalarında risk
faktörlerinin etkinliğinin değerlendirilmesidir. Geriye-yönelik ve kesitsel
olarak tasarlanan bu çalışma, 2008-2009 yılları arasında gerçekleştirildi. TGM
açısından tetkik edilen VTE hastaları çalışmaya alındı. Toplam 109 hastada ilk
VTE atak yaşı ortalaması 42.6±14.1 yıl idi. Ellidokuz (%54.1) hasta erkekti.
Otuzüç (%30.3) hastada birincil VTE mevcut iken 46 (%42.6) hastada rVTE
bulunmaktaydı. Tek değişkenli analizde artmış rVTE oranı ile belirgin
birliktelik gösteren değişkenler yaş ≥40 yıl, ilk atağın hastane-içi’nde
olması, malignite, dahili hastalık, TGM, faktör V Leiden ve protrombin G20210A
mutasyonu idi. Farklı mutasyon sayılarının rVTE için analizi, mutasyonu olmayan
ve tek gen mutasyonu olan hastalar haricinde belirgin farklılık göstermektedir.
Ek olarak, artan hasta başına klinik risk faktörü ve TGM sayısı rVTE ile hem
tek değişkenli hem de çok değişkenli analizlerde belirgin ilişkili saptandı. Tekrarlayan
VTE açısından TGM’ları, rVTE riskini arttırmakta, ancak tek başlarına önemli
bir rol oynamıyor gibi görünmektedir. Ancak, TGM da dahil olmak üzere klinik
risk faktörlerinin eş zamanlı birlikteliği, rVTE’nin öngörüsünde daha önemli
görünmektedir. 

Anahtar Kelimeler

Venöz tromboemboli, Tekrarlayan, Faktör V Leiden, Protrombin G20210A, Metilentetrahidrofolat redüktaz C677T, Metilenttrahidrofolat redüktaz A1298C

Kaynakça

• 1. Palareti G. Recurrent venous thromboembolism: what is the risk and how to prevent it. Scientifica (Cairo). 2012;2012:391734.
• 2. Connors JM. Thrombophilia Testing and Venous Thrombosis. N Engl J Med. 2017;377(12):1177-87.
• 3. Almawi WY, Tamim H, Kreidy R, Timson G, Rahal E, Nabulsi M, et al. A case control study on the contribution of factor V-Leiden, prothrombin G20210A, and MTHFR C677T mutations to the genetic susceptibility of deep venous thrombosis. J Thromb Thrombolysis. 2005;19(3):189-96.
• 4. Baglin T, Luddington R, Brown K, Baglin C. Incidence of recurrent venous thromboembolism in relation to clinical and thrombophilic risk factors: prospective cohort study. Lancet. 2003;362(9383):523-6.
• 5. Christiansen SC, Cannegieter SC, Koster T, Vandenbroucke JP, Rosendaal FR. Thrombophilia, clinical factors, and recurrent venous thrombotic events. JAMA. 2005;293(19):2352-61.
• 6. Mazzolai L, Duchosal MA. Hereditary thrombophilia and venous thromboembolism: critical evaluation of the clinical implications of screening. Eur J Vasc Endovasc Surg. 2007;34(4):483-8.
• 7. Van Cott EM, Laposata M, Prins MH. Laboratory evaluation of hypercoagulability with venous or arterial thrombosis. Arch Pathol Lab Med. 2002;126(11):1281-95.
• 8. Spencer FA, Emery C, Joffe SW, Pacifico L, Lessard D, Reed G, et al. Incidence rates, clinical profile, and outcomes of patients with venous thromboembolism. The Worcester VTE study. J Thromb Thrombolysis. 2009;28(4):401-9.
• 9. Ho W, Hankey GJ, Quinlan DJ, Eikelboom JW. Risk of recurrent venous thromboembolism in patients with common thrombophilia: A systematic review. Archives of Internal Medicine. 2006;166(7):729-36.
• 10. Kovac M, Mikovic D, Antonijevic N, Rakicevic L, Djordjevic V, Radojkovic D, et al. FV Leiden mutation and risk of recurrent venous thromboembolism in Serbian population. J Thromb Thrombolysis. 2008;25(3):284-7.
• 11. Piazza G. Thrombophilia Testing, Recurrent Thrombosis, and Women’s Health. Circulation. 2014;130(3):283.
• 12. Santamaria MG, Agnelli G, Taliani MR, Prandoni P, Moia M, Bazzan M, et al. Thrombophilic abnormalities and recurrence of venous thromboembolism in patients treated with standardized anticoagulant treatment. Thromb Res. 2005;116(4):301-6.
• 13. Simioni P, Prandoni P, Lensing AW, Manfrin D, Tormene D, Gavasso S, et al. Risk for subsequent venous thromboembolic complications in carriers of the prothrombin or the factor V gene mutation with a first episode of deep-vein thrombosis. Blood. 2000;96(10):3329-33.
• 14. Marchiori A, Mosena L, Prins MH, Prandoni P. The risk of recurrent venous thromboembolism among heterozygous carriers of factor V Leiden or prothrombin G20210A mutation. A systematic review of prospective studies. Haematologica. 2007;92(8):1107-14.
• 15. Coppens M, Reijnders JH, Middeldorp S, Doggen CJ, Rosendaal FR. Testing for inherited thrombophilia does not reduce the recurrence of venous thrombosis. J Thromb Haemost. 2008;6(9):1474-7.
• 16. De Stefano V, Martinelli I, Mannucci PM, Paciaroni K, Chiusolo P, Casorelli I, et al. The risk of recurrent deep venous thrombosis among heterozygous carriers of both factor V Leiden and the G20210A prothrombin mutation. N Engl J Med. 1999;341(11):801-6.
• 17. Mansilha A, Araujo F, Severo M, Sampaio SM, Toledo T, Albuquerque R. Genetic polymorphisms and risk of recurrent deep venous thrombosis in young people: prospective cohort study. Eur J Vasc Endovasc Surg. 2005;30(5):545-9.
• 18. Miles JS, Miletich JP, Goldhaber SZ, Hennekens CH, Ridker PM. G20210A mutation in the prothrombin gene and the risk of recurrent venous thromboembolism. J Am Coll Cardiol. 2001;37(1):215-8.
• 19. Prandoni P, Noventa F, Ghirarduzzi A, Pengo V, Bernardi E, Pesavento R, et al. The risk of recurrent venous thromboembolism after discontinuing anticoagulation in patients with acute proximal deep vein thrombosis or pulmonary embolism. A prospective cohort study in 1,626 patients. Haematologica. 2007;92(2):199-205.
• 20. Lijfering WM, Middeldorp S, Veeger NJ, Hamulyak K, Prins MH, Buller HR, et al. Risk of recurrent venous thrombosis in homozygous carriers and double heterozygous carriers of factor V Leiden and prothrombin G20210A. Circulation. 2010;121(15):1706-12.
• 21. Simioni P, Prandoni P, Lensing AW, Scudeller A, Sardella C, Prins MH, et al. The risk of recurrent venous thromboembolism in patients with an Arg506-->Gln mutation in the gene for factor V (factor V Leiden). N Engl J Med. 1997;336(6):399-403.
• 22. Ridker PM, Miletich JP, Stampfer MJ, Goldhaber SZ, Lindpaintner K, Hennekens CH. Factor V Leiden and risks of recurrent idiopathic venous thromboembolism. Circulation. 1995;92(10):2800-2.