Tanımlanabilir Edinsel Risk Faktörleri Olmayan Pulmoner Tromboembolizmli Hastalarda Kalıtsal Risk Faktörlerinin Dağılımı
Öz
Amaç: Bu çalışmada edinilmiş risk faktörü olmayan pulmoner tromboemboli (PTE) hastalarında kalıtsal risk faktörlerinin dağılımının araştırılması ve genetik faktörler ile emboli kaynaklı erken mortalite riski arasındaki ilişkinin araştırılması amaçlanmıştır.
Gereç ve Yöntemler: PTE tanısı almış 295 hastanın verileri geriye dönük olarak incelendi. Bunlardan edinilmiş risk faktörü olmayan ve faktör V Leiden (FVL), protrombin (PT) G20210A, metilentetrahidrofolat redüktaz (MTHFR) C677T, MTHFR A1298C, plazminojen aktivatör inhibitörü (PAI) 4G/5G, faktör XIII, antitrombin (AT) III, protein C, protein S ve aktive protein C direnci (APCR) dahil olmak üzere kalıtsal risk faktörleri açısından taranan 44 hasta çalışmaya dahil edildi.
Bulgular: Hastaların 14'ü (%31,8) kadın ve 30'u (%68,2) erkek olup, yaş ortalaması 46,5±17,3 yıl idi. Kalıtsal risk faktörleri arasında en sık görülen homozigot mutasyonlar MTHFR A1298C (n=10, %22,7), PAI 4G/5G (n=9, %20,5) ve FVL (n=5, %11,4) iken, en sık görülen heterozigot mutasyonlar PAI 4G/5G (n=26, %59,1), MTHFR A1298C (n=19, %43,2) ve MTHFR C677T (n=16, %36,4) idi. Tekrarlayan PTE öyküsü olan 10 (%52,6) hastada heterozigot MTHFR A1298C mutasyonu tespit edildi.
Sonuç: Bu çalışma, PTE'li hastalarda PAI 4G/5G, MTHFR A1298C, MTHFR C677T, FVL, faktör XIII ve PT G20210A gibi genetik mutasyonların varlığını vurgulamaktadır. Sonuçlar, özellikle edinilmiş risk faktörü olmayan, tekrarlayan PTE öyküsü olmayan veya herhangi bir aile üyesinde trombofili olmayan 50 yaş altı hastalarda genetik nedenlerin yüksek prevalansta olduğunu göstermektedir.
Anahtar Kelimeler
Pulmoner tromboemboli edinilmiş risk faktörleri kalıtsal risk faktörleri
Kaynakça
- Nizankowska-Mogilnicka E, Adamek L, Grzanka P, Domagala TB, Sanak M, Krzanowski M, et al. Genetic polymorphisms associated with acute pulmonary embolism and deep venous thrombosis. Eur Respir J. 2003;21(1):25-30.
- Hodeib H, Youssef A, Allam AA, Selim A, Tawfik MA, Abosamak MF, et al. Genetic risk profiling associated with recurrent unprovoked venous thromboembolism. Genes (Basel). 2021;12(6):874.
- Arseven O, Bingöl Z, Öngen HG, Uzun O, Okumuş NG, editors. Turkish Thoracic Society pulmonary thromboembolism diagnosis and treatment consensus report. Ankara: Optimus Publishing; 2021. Turkish.
- Turan O, Ündar B, Günay T, Akkoçlu A. Investigation of inherited thrombophilias in patients with pulmonary embolism. Blood Coagul Fibrinolysis. 2013;24(2):140-9.
- Konstantinides SV, Meyer G, Becattini C, Bueno H, Geersing GJ, Harjola VP, et al. 2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS). Eur Heart J. 2020;41(4):543-603.
- Şimşek F, Ceylan M, Bilge N. The relationship between etiology and genetic polymorphism in adults with cerebral venous thrombosis. Duzce Med J. 2019;21(3):166-71. Turkish.
- Rossi E, Za T, Ciminello A, Leone G, Stefano V. The risk of symptomatic pulmonary embolism due to proximal deep venous thrombosis differs in patients with different types of inherited thrombophilia. Thromb Haemost. 2008;99(6):1030-4.
- Komsa-Penkova R, Tonchev PT, Kovacheva KS, Georgieva GB, Ivanov YY, Ivanov PD, et al. Predisposition to thrombophilia and hypofibrinolysis in pulmonary embolism: analysis of inherited factors. J Biomed Clin Res. 2013;6(2):73-81.
- Brandimarti F, Alessandrini F, Pesaresi M, Catalani C, De Angelis L, Galeazzi R, et al. Investigation on genetic thrombophilic factors in FFPE autopsy tissue from subjects who died from pulmonary embolism. Int J Legal Med. 2017;131(2):447-58.
- Gurgey A, Haznedaroglu IC, Egesel T, Buyukasik Y, Ozcebe OI, Sayinalp N, et al. Two common genetic thrombotic risk factors: factor V Leiden and prothrombin G20210A in adult Turkish patients with thrombosis. Am J Hematol. 2001;67(2):107-11.
- Kalkanli S, Ayyildiz O, Tiftik N, Batun S, Isikdogan A, Ince H, et al. E. Factor V Leiden mutation in venous thrombosis in southeast Turkey. Angiology. 2006;57(2):193-6.
- Kupeli E, Verdi H, Simsek A, Atac FB, Eyuboglu FO. Genetic mutations in Turkish population with pulmonary embolism and deep venous thrombosis. Clin Appl Thromb Hemost. 2011;17(6):E87-94.
- Oguzulgen IK, Yilmaz E, Demirtas S, Erkekol FO, Ekim N, Demir N, et al. The role of plasminogen activator inhibitor-1 polymorphism, factor-V-Leiden, and prothrombin-20210 mutations in pulmonary thromboembolism. Clin Appl Thromb Hemost. 2009;15(1):73-7.
- Okumus G, Kiyan E, Arseven O, Tabak L, Diz-Kucukkaya R, Unlucerci Y, et al. Hereditary thrombophilic risk factors and venous thromboembolism in Istanbul, Turkey: the role in different clinical manifestations of venous thromboembolism. Clin Appl Thromb Hemost. 2008;14(2):168-73.
- Dölek B, Eraslan S, Eroğlu S, Kesim BE, Ulutin T, Yalçıner A, et al. Molecular analysis of factor V Leiden, factor V Hong Kong, factor II G20210A, methylenetetrahydrofolate reductase C677T, and A1298C mutations related to Turkish thrombosis patients. Clin Appl Thromb Hemost. 2007;13(4):435-8.
- Erkekol FO, Ulu A, Numanoglu N, Akar N. High plasma levels of factor VIII: an important risk factor for isolated pulmonary embolism. Respirology. 2006;11(1):70-4.
The Distribution of Hereditary Risk Factors in Patients with Pulmonary Thromboembolism without Identifiable Acquired Risk Factors
Öz
Aim: This study aimed to investigate the distribution of hereditary risk factors in patients with pulmonary thromboembolism (PTE) who have no acquired risk factors and to explore the relationship between genetic factors and the early mortality risk of embolism.
Material and Methods: Data from 295 patients diagnosed with PTE were examined retrospectively. Of these, 44 patients who had no acquired risk factors and were screened for hereditary risk factors, including factor V Leiden (FVL), prothrombin (PT) G20210A, methylenetetrahydrofolate reductase (MTHFR) C677T, MTHFR A1298C, plasminogen activator inhibitor (PAI) 4G/5G, factor XIII, antithrombin (AT) III, protein C, protein S, and activated protein C resistance (APCR), were included in the study.
Results: Of the patients, 14 (31.8%) were female and 30 (68.2%) were male, with a mean age of 46.5±17.3 years. Among the hereditary risk factors, the most common homozygous mutations were MTHFR A1298C (n=10, 22.7%), PAI 4G/5G (n=9, 20.5%), and FVL (n=5, 11.4%), while the most common heterozygous mutations were PAI 4G/5G (n=26, 59.1%), MTHFR A1298C (n=19, 43.2%), and MTHFR C677T (n=16, 36.4%). The heterozygous MTHFR A1298C mutation was detected in 10 (52.6%) patients with a history of recurrent PTE.
Conclusion: This study highlights the presence of genetic mutations such as PAI 4G/5G, MTHFR A1298C, MTHFR C677T, FVL, factor XIII, and PT G20210A in patients with PTE. The results show a high prevalence of genetic causes, especially in patients under 50 years of age with no acquired risk factors, no history of recurrent PTE or thrombophilia in any family member.
Anahtar Kelimeler
Pulmonary thrombo embolism acquired risk factors hereditary risk factors
Kaynakça
- Nizankowska-Mogilnicka E, Adamek L, Grzanka P, Domagala TB, Sanak M, Krzanowski M, et al. Genetic polymorphisms associated with acute pulmonary embolism and deep venous thrombosis. Eur Respir J. 2003;21(1):25-30.
- Hodeib H, Youssef A, Allam AA, Selim A, Tawfik MA, Abosamak MF, et al. Genetic risk profiling associated with recurrent unprovoked venous thromboembolism. Genes (Basel). 2021;12(6):874.
- Arseven O, Bingöl Z, Öngen HG, Uzun O, Okumuş NG, editors. Turkish Thoracic Society pulmonary thromboembolism diagnosis and treatment consensus report. Ankara: Optimus Publishing; 2021. Turkish.
- Turan O, Ündar B, Günay T, Akkoçlu A. Investigation of inherited thrombophilias in patients with pulmonary embolism. Blood Coagul Fibrinolysis. 2013;24(2):140-9.
- Konstantinides SV, Meyer G, Becattini C, Bueno H, Geersing GJ, Harjola VP, et al. 2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS). Eur Heart J. 2020;41(4):543-603.
- Şimşek F, Ceylan M, Bilge N. The relationship between etiology and genetic polymorphism in adults with cerebral venous thrombosis. Duzce Med J. 2019;21(3):166-71. Turkish.
- Rossi E, Za T, Ciminello A, Leone G, Stefano V. The risk of symptomatic pulmonary embolism due to proximal deep venous thrombosis differs in patients with different types of inherited thrombophilia. Thromb Haemost. 2008;99(6):1030-4.
- Komsa-Penkova R, Tonchev PT, Kovacheva KS, Georgieva GB, Ivanov YY, Ivanov PD, et al. Predisposition to thrombophilia and hypofibrinolysis in pulmonary embolism: analysis of inherited factors. J Biomed Clin Res. 2013;6(2):73-81.
- Brandimarti F, Alessandrini F, Pesaresi M, Catalani C, De Angelis L, Galeazzi R, et al. Investigation on genetic thrombophilic factors in FFPE autopsy tissue from subjects who died from pulmonary embolism. Int J Legal Med. 2017;131(2):447-58.
- Gurgey A, Haznedaroglu IC, Egesel T, Buyukasik Y, Ozcebe OI, Sayinalp N, et al. Two common genetic thrombotic risk factors: factor V Leiden and prothrombin G20210A in adult Turkish patients with thrombosis. Am J Hematol. 2001;67(2):107-11.
- Kalkanli S, Ayyildiz O, Tiftik N, Batun S, Isikdogan A, Ince H, et al. E. Factor V Leiden mutation in venous thrombosis in southeast Turkey. Angiology. 2006;57(2):193-6.
- Kupeli E, Verdi H, Simsek A, Atac FB, Eyuboglu FO. Genetic mutations in Turkish population with pulmonary embolism and deep venous thrombosis. Clin Appl Thromb Hemost. 2011;17(6):E87-94.
- Oguzulgen IK, Yilmaz E, Demirtas S, Erkekol FO, Ekim N, Demir N, et al. The role of plasminogen activator inhibitor-1 polymorphism, factor-V-Leiden, and prothrombin-20210 mutations in pulmonary thromboembolism. Clin Appl Thromb Hemost. 2009;15(1):73-7.
- Okumus G, Kiyan E, Arseven O, Tabak L, Diz-Kucukkaya R, Unlucerci Y, et al. Hereditary thrombophilic risk factors and venous thromboembolism in Istanbul, Turkey: the role in different clinical manifestations of venous thromboembolism. Clin Appl Thromb Hemost. 2008;14(2):168-73.
- Dölek B, Eraslan S, Eroğlu S, Kesim BE, Ulutin T, Yalçıner A, et al. Molecular analysis of factor V Leiden, factor V Hong Kong, factor II G20210A, methylenetetrahydrofolate reductase C677T, and A1298C mutations related to Turkish thrombosis patients. Clin Appl Thromb Hemost. 2007;13(4):435-8.
- Erkekol FO, Ulu A, Numanoglu N, Akar N. High plasma levels of factor VIII: an important risk factor for isolated pulmonary embolism. Respirology. 2006;11(1):70-4.
Ayrıntılar
| Birincil Dil | İngilizce |
|---|---|
| Konular | Göğüs Hastalıkları |
| Bölüm | Araştırma Makalesi |
| Yazarlar | |
| Erken Görünüm Tarihi | 21 Nisan 2025 |
| Yayımlanma Tarihi | 30 Nisan 2025 |
| Gönderilme Tarihi | 11 Kasım 2024 |
| Kabul Tarihi | 25 Mart 2025 |
| Yayımlandığı Sayı | Yıl 2025 |
Kaynak Göster
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