• 新疆維吾爾自治區(qū)人民醫(yī)院血管外科 (烏魯木齊 830001);

目的 總結(jié)遺傳性易栓癥的研究進展。
方法 復(fù)習(xí)近年來有關(guān)遺傳性易栓癥的文獻報道并進行分析。
結(jié)果 易栓癥的遺傳性危險因素存在著種族差異。白種人以活化蛋白C抵抗、凝血因子V Leiden突變、亞甲基四氫葉酸還原酶C677T突變及凝血酶原G20120A突變?yōu)橹饕z傳易感因素; 中國人群則以蛋白C系統(tǒng)異常及高同型半胱氨酸血癥為主。多個遺傳性危險因素的聯(lián)合存在增加了首發(fā)和復(fù)發(fā)靜脈血栓的風(fēng)險。
結(jié)論 進一步探索遺傳性危險因素與易栓癥的關(guān)系, 對于預(yù)測及預(yù)防靜脈血栓栓塞癥的發(fā)生，降低其發(fā)病率有著十分重要的意義。

引用本文： 姜孝奎,戈小虎. 遺傳性易栓癥的研究現(xiàn)狀. 中國普外基礎(chǔ)與臨床雜志, 2010, 17(7): 686-689. doi: 復(fù)制

1. Egeberg O. On the natural blood coagulation inhibitor system. Investigations of inhibitor factors based on antithrombin deficient blood [J]. Thromb Diath Haemorrh， 1965; 14(34): 473489.
2. 王鴻利. 血液學(xué)和血液學(xué)檢驗 [M]. 第2版. 北京: 人民衛(wèi)生出版社, 1997: 292293.
3. Tripodi A. A review of the clinical and diagnostic utility of laboratory tests for the detection of congenital thrombophilia [J]. Semin Thromb Hemost, 2005; 31(1): 2532.
4. 趙永強. 我國靜脈血栓栓塞癥的研究現(xiàn)狀 [J]. 中華內(nèi)科雜志, 2005; 44(2): 8384.
5. Bertina RM, Koelemen BP, Koster T, et al. Mutation in blood coagulation factor Ⅴ ssociated with resistance to activated protein C [J]. Nature, 1994; 369(6475): 6467.
6. Rees DC, Cox M, Clegg JB. World distribution of factor Ⅴ Leiden [J]. Lancet. 1995; 346(8983): 11331134.
7. Nicolaes GA, Dahlbck B. Factor V and thrombotic disease: description of a janusfaced protein [J]. Arterioscler Thromb Vasc Biol, 2002; 22(4): 530538.
8. Lucotte G, Mercier G. Population genetics of factor Ⅴ Leiden in Europe [J]. Blood Cells Mol Dis, 2001; 27(2): 362367.
9. Lu Y, Zhao Y, Liu G, et al. Factor V gene G1691A mutation, prothrombin gene G20210A mutation, and MTHFR gene C677T mutation are not risk factors for pulmonary thromboembolism in Chinese population [J]. Thromb Res, 2002; 106(1): 712.
10. Jun ZJ , Ping T, Lei Y, et al. Prevalence of factor Ⅴ Leiden and prothrombin G20210A mutations in Chinese patients with deep venous thrombosis and pulmonary embolism [J]. Clin Lab Haematol, 2006; 28(2): 111116.
11. Almawi WY, Tamim H, Kreidy R, 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]. J Thromb Thrombolysis, 2005; 19(3): 189196.
12. Heit JA, Sobell JL, Li H, et al. The incidence of venous thromboembolism among factor Ⅴ Leiden carriers: a communitybased cohort study [J]. J Thromb Haemost, 2005; 3(2): 305311.
13. Oger E, Lacut K, Le Gal G, et al. Is APC resistance a risk factor for venous thromboembolism in patients over 70 years? [J]. Thromb Haemost, 2002; 88(4): 587591.
14. 賀立山. 血液病家族新成員-易栓癥 [J]. 醫(yī)學(xué)新知雜志, 2008; 18(3): 129133.
15. Bauer KA. The thrombophilias: welldefined risk factors with uncertain therapeutic implications [J]. Ann Intern Med 2001; 135(5): 367373.
16. Crowther MA, Kelton JG. Congenital thrombophilic states associated with venous thrombosis: a qualitative overview and proposed classification system [J]. Ann Intern Med 2003; 138(2): 128134.
17. Simioni P, Tormene D, Spiezia L, et al. Inherited thrombophilia and venous thromboembolism [J]. Semin Thromb Hemost, 2006; 32(7): 700708.
18. NizankowskaMogilnicka E, Adamek L, Grzanka P, et al. Genetic polymorphisms associated with acute pulmonary embolism and deep venous thrombosis [J]. Eur Respir J, 2003; 21(1): 2530.
19. De Stefano V, Rossi E, Paciaroni K, et al. Different circumstances of the first venous thromboembolism among younger or older heterozygous carriers of the G20210A polymorphism in the prothrombin gene [J]. Haematologica, 2003; 88(1): 6166.
20. Emmerich J, Rosendaal FR, Cattaneo M, et al. Combined effect of factor Ⅴ Leiden and prothrombin 20210A on the risk of venous thromboembolism-pooled analysis of 8 casecontrol studies including 2 310 cases and 3 204 controls. Study Group for PooledAnalysis in Venous Thromboembolism [J]. Thromb Haemost, 2001; 86(3): 809816.
21. Varga EA, Moll S. Cardiology patient pages. Prothrombin 20210 mutation (factor Ⅱ mutation) [J]. Circulation, 2004;110(3): e15e18.
22. Griffin JH, Evatt B, Zimmerman TS, et al. Deficiency of protein C in congenital thrombotic disease [J]. J Clin Invest, 1981; 68(5): 13701373.
23. 劉麗, 郭文茹, 賀立山, 等. 遺傳性蛋白C缺陷癥家系的一個基因突變 [J]. 中華血液學(xué)雜志, 2003; 24(3): 115118.
24. 劉麗, 賀立山, 楊爽, 等. 遺傳性蛋白S缺陷癥一個新的基因突變 [J]. 中華血液學(xué)雜志, 2001; 22(9): 457460.
25. Kallel L, Matri S, Karoui S, et al. Deep venous thrombosis related to protein S deficiency revealing celiac disease [J]. Am J Gastroenterol, 2009; 104(1): 256257.
26. Tait RC, Walker ID, Reitsma PH, et al. Prevalence of protein C deficiency in the healthy population [J]. Thromb Haemost, 1995; 73(1): 8793.
27. Tait RC, Walker ID, Perry DJ, et al. Prevalence of antithrombin deficiency in the healthy population [J]. Br J Haematol, 1994; 87(1): 106112.
28. McColl M, Tait RC, Walker ID, et al. Low thrombosis rate seen in blood donors and their relatives with inherited deficiencies of antithrombin and protein C: correlation with type of defect, family history, and absence of the factor Ⅴ Leiden mutation [J]. Blood Coagul Fibrinolysis, 1996; 7(7): 689694.
29. Rosendaal FR. Risk factors for venous thrombotic disease [J]. Thromb Haemost, 1999; 82(2): 610619.
30. 臧凡, 趙永桔, 吳方. 靜脈血栓栓塞癥的遺傳易感性及其基因篩查 [J]. 國際內(nèi)科學(xué)雜志, 2007; 34(11): 673675.
31. Chen TY, Su WC, Tsao CJ. Incidence of thrombophilia detected in southern Taiwanese patients with venous thrombosis [J]. Ann Hematol, 2003; 82(2): 114117.
32. Undas A, Brozek J, Szczeklik A. Homocysteine and thrombosis: from basic science to clinical evidence [J]. Thromb Haemost, 2005; 94(5): 907915.
33. Fermo I, Vigano’ D’Angelo S, Paroni R, et al. Prevalence of moderate hyperhomocysteinemia in patients with earlyonset venous and arterial occlusive disease [J]. Ann Intern Med, 1995; 123(10): 747753.
34. Den Heijer M, Koster T, Blom HJ, et al. Hyperhomocysteinemia as a risk factor for deepvein thrombosis [J]. N Engl J Med, 1996; 334(12): 759762.
35. Simioni P, Prandoni P, Burlina A, et al. Hyperhomocysteinemia and deepvein thrombosis: a casecontrol study [J]. Thromb Haemost, 1996; 76(6): 883886.
36. 趙永強. 易栓癥研究概況 [J]. 中國實用內(nèi)科雜志, 2007; 27(1): 4952.
37. Den Heijer M, Lewington S, Clarke R. Homocysteine, MTHFR and risk of venous thrombosis: a metaanalysis of published epidemiological studies [J]. J Thromb Haemost, 2005; 3(2): 292299.
38. Oger E, Lacut K, Le Gal G, et al. Hyperhomocysteinemia and low B vitamin levels are independently associated with venous thromboembolism: results from the EDITH study: a hospitalbased casecontrol study [J]. J Thromb Haemost, 2006; 4(4): 793799.
39. Beutler E, Lichtman MA, Coller BS, et al. Willianms Hematology [M]. 6th edition. New York: McGrawHill, 2001: 16971707.
  1. 1. Egeberg O. On the natural blood coagulation inhibitor system. Investigations of inhibitor factors based on antithrombin deficient blood [J]. Thromb Diath Haemorrh， 1965; 14(34): 473489.
  2. 2. 王鴻利. 血液學(xué)和血液學(xué)檢驗 [M]. 第2版. 北京: 人民衛(wèi)生出版社, 1997: 292293.
  3. 3. Tripodi A. A review of the clinical and diagnostic utility of laboratory tests for the detection of congenital thrombophilia [J]. Semin Thromb Hemost, 2005; 31(1): 2532.
  4. 4. 趙永強. 我國靜脈血栓栓塞癥的研究現(xiàn)狀 [J]. 中華內(nèi)科雜志, 2005; 44(2): 8384.
  5. 5. Bertina RM, Koelemen BP, Koster T, et al. Mutation in blood coagulation factor Ⅴ ssociated with resistance to activated protein C [J]. Nature, 1994; 369(6475): 6467.
  6. 6. Rees DC, Cox M, Clegg JB. World distribution of factor Ⅴ Leiden [J]. Lancet. 1995; 346(8983): 11331134.
  7. 7. Nicolaes GA, Dahlbck B. Factor V and thrombotic disease: description of a janusfaced protein [J]. Arterioscler Thromb Vasc Biol, 2002; 22(4): 530538.
  8. 8. Lucotte G, Mercier G. Population genetics of factor Ⅴ Leiden in Europe [J]. Blood Cells Mol Dis, 2001; 27(2): 362367.
  9. 9. Lu Y, Zhao Y, Liu G, et al. Factor V gene G1691A mutation, prothrombin gene G20210A mutation, and MTHFR gene C677T mutation are not risk factors for pulmonary thromboembolism in Chinese population [J]. Thromb Res, 2002; 106(1): 712.
  10. 10. Jun ZJ , Ping T, Lei Y, et al. Prevalence of factor Ⅴ Leiden and prothrombin G20210A mutations in Chinese patients with deep venous thrombosis and pulmonary embolism [J]. Clin Lab Haematol, 2006; 28(2): 111116.
  11. 11. Almawi WY, Tamim H, Kreidy R, 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]. J Thromb Thrombolysis, 2005; 19(3): 189196.
  12. 12. Heit JA, Sobell JL, Li H, et al. The incidence of venous thromboembolism among factor Ⅴ Leiden carriers: a communitybased cohort study [J]. J Thromb Haemost, 2005; 3(2): 305311.
  13. 13. Oger E, Lacut K, Le Gal G, et al. Is APC resistance a risk factor for venous thromboembolism in patients over 70 years? [J]. Thromb Haemost, 2002; 88(4): 587591.
  14. 14. 賀立山. 血液病家族新成員-易栓癥 [J]. 醫(yī)學(xué)新知雜志, 2008; 18(3): 129133.
  15. 15. Bauer KA. The thrombophilias: welldefined risk factors with uncertain therapeutic implications [J]. Ann Intern Med 2001; 135(5): 367373.
  16. 16. Crowther MA, Kelton JG. Congenital thrombophilic states associated with venous thrombosis: a qualitative overview and proposed classification system [J]. Ann Intern Med 2003; 138(2): 128134.
  17. 17. Simioni P, Tormene D, Spiezia L, et al. Inherited thrombophilia and venous thromboembolism [J]. Semin Thromb Hemost, 2006; 32(7): 700708.
  18. 18. NizankowskaMogilnicka E, Adamek L, Grzanka P, et al. Genetic polymorphisms associated with acute pulmonary embolism and deep venous thrombosis [J]. Eur Respir J, 2003; 21(1): 2530.
  19. 19. De Stefano V, Rossi E, Paciaroni K, et al. Different circumstances of the first venous thromboembolism among younger or older heterozygous carriers of the G20210A polymorphism in the prothrombin gene [J]. Haematologica, 2003; 88(1): 6166.
  20. 20. Emmerich J, Rosendaal FR, Cattaneo M, et al. Combined effect of factor Ⅴ Leiden and prothrombin 20210A on the risk of venous thromboembolism-pooled analysis of 8 casecontrol studies including 2 310 cases and 3 204 controls. Study Group for PooledAnalysis in Venous Thromboembolism [J]. Thromb Haemost, 2001; 86(3): 809816.
  21. 21. Varga EA, Moll S. Cardiology patient pages. Prothrombin 20210 mutation (factor Ⅱ mutation) [J]. Circulation, 2004;110(3): e15e18.
  22. 22. Griffin JH, Evatt B, Zimmerman TS, et al. Deficiency of protein C in congenital thrombotic disease [J]. J Clin Invest, 1981; 68(5): 13701373.
  23. 23. 劉麗, 郭文茹, 賀立山, 等. 遺傳性蛋白C缺陷癥家系的一個基因突變 [J]. 中華血液學(xué)雜志, 2003; 24(3): 115118.
  24. 24. 劉麗, 賀立山, 楊爽, 等. 遺傳性蛋白S缺陷癥一個新的基因突變 [J]. 中華血液學(xué)雜志, 2001; 22(9): 457460.
  25. 25. Kallel L, Matri S, Karoui S, et al. Deep venous thrombosis related to protein S deficiency revealing celiac disease [J]. Am J Gastroenterol, 2009; 104(1): 256257.
  26. 26. Tait RC, Walker ID, Reitsma PH, et al. Prevalence of protein C deficiency in the healthy population [J]. Thromb Haemost, 1995; 73(1): 8793.
  27. 27. Tait RC, Walker ID, Perry DJ, et al. Prevalence of antithrombin deficiency in the healthy population [J]. Br J Haematol, 1994; 87(1): 106112.
  28. 28. McColl M, Tait RC, Walker ID, et al. Low thrombosis rate seen in blood donors and their relatives with inherited deficiencies of antithrombin and protein C: correlation with type of defect, family history, and absence of the factor Ⅴ Leiden mutation [J]. Blood Coagul Fibrinolysis, 1996; 7(7): 689694.
  29. 29. Rosendaal FR. Risk factors for venous thrombotic disease [J]. Thromb Haemost, 1999; 82(2): 610619.
  30. 30. 臧凡, 趙永桔, 吳方. 靜脈血栓栓塞癥的遺傳易感性及其基因篩查 [J]. 國際內(nèi)科學(xué)雜志, 2007; 34(11): 673675.
  31. 31. Chen TY, Su WC, Tsao CJ. Incidence of thrombophilia detected in southern Taiwanese patients with venous thrombosis [J]. Ann Hematol, 2003; 82(2): 114117.
  32. 32. Undas A, Brozek J, Szczeklik A. Homocysteine and thrombosis: from basic science to clinical evidence [J]. Thromb Haemost, 2005; 94(5): 907915.
  33. 33. Fermo I, Vigano’ D’Angelo S, Paroni R, et al. Prevalence of moderate hyperhomocysteinemia in patients with earlyonset venous and arterial occlusive disease [J]. Ann Intern Med, 1995; 123(10): 747753.
  34. 34. Den Heijer M, Koster T, Blom HJ, et al. Hyperhomocysteinemia as a risk factor for deepvein thrombosis [J]. N Engl J Med, 1996; 334(12): 759762.
  35. 35. Simioni P, Prandoni P, Burlina A, et al. Hyperhomocysteinemia and deepvein thrombosis: a casecontrol study [J]. Thromb Haemost, 1996; 76(6): 883886.
  36. 36. 趙永強. 易栓癥研究概況 [J]. 中國實用內(nèi)科雜志, 2007; 27(1): 4952.
  37. 37. Den Heijer M, Lewington S, Clarke R. Homocysteine, MTHFR and risk of venous thrombosis: a metaanalysis of published epidemiological studies [J]. J Thromb Haemost, 2005; 3(2): 292299.
  38. 38. Oger E, Lacut K, Le Gal G, et al. Hyperhomocysteinemia and low B vitamin levels are independently associated with venous thromboembolism: results from the EDITH study: a hospitalbased casecontrol study [J]. J Thromb Haemost, 2006; 4(4): 793799.
  39. 39. Beutler E, Lichtman MA, Coller BS, et al. Willianms Hematology [M]. 6th edition. New York: McGrawHill, 2001: 16971707.