Aims: To assess the prevalence of thrombophilia among Chinese women with venous thromboembolism (VTE) developed during pregnancy. Methods: Based on information from a tertiary teaching unit, all recorded cases of deep vein thrombosis (DVT) and pulmonary embolism (PE) during pregnancy diagnosed between 1997 and 2005, were assessed for prevalence of thrombophilia. Fifty-five healthy women, who had at least one normal pregnancy but without any previous history of VTE, were recruited as controls. Results: A total of 44 subjects completed thrombophilia screening, of whom 5 (11%) were confirmed to have thrombophilia [protein C (PC) deficiency (2), protein S (PS) deficiency (1), combined PC & PS deficiency (1) and antithrombin III deficiency (1)]. Homozygous 5,10-methylenetetrahydrofolate reductase (C677T) gene mutation was found in 6 (14%) subjects but not in the controls. There was no antiphospholipid syndrome, activated PC resistance, factor V Leiden or prothrombin gene mutations. Conclusion: In the Chinese population, PS and PC deficiencies are common thrombophilia for VTE during pregnancy and thrombophilia screening should be recommended in all pregnant women who suffer from VTE.

Keywords:
Thrombophilia, Chinese, Pregnancy
1.
De Swiet M: Thromboembolism. Clin Haematol 1985;14:643–660.
2.
Tso SC, Wong V, Chan V, Chan TK, Ma HK, Todd D: Deep vein thrombosis and changes in coagulation and fibrinolysis after gynaecological operations in Chinese: the effect of oral contraceptives and malignant disease. Br J Haematol 1980;46:603–612.
3.
Chau KY, Yuen ST, Wong MP: Clinicopathological pattern of pulmonary thromboembolism in Chinese autopsy patients: comparison with Caucasian series. Pathology 1997;29:263–266.
4.
Woo KS, Mak GY, Sung JY, Woo JL, Metreweli C, Vallance-Owen J: The incidence and clinical pattern of deep vein thrombosis in the Chinese in Hong Kong. Singapore Med J 1988;29:357–359.
5.
Chan LY, Tam WH, Lau TK: Venous thromboembolism in pregnant Chinese women. Obstet Gynecol 2001;98:471–475.
6.
Tam WH, Lau TK, Chan LY: Thromboembolism in pregnancy amongst Chinese. J Paediatr Obstet Gynaecol 2004;30:78–83.
7.
Liu S, Rouleau J, Joseph KS, Sauve R, Liston RM, Young D, Kramer MS: Epidemiology of pregnancy-associated venous thromboembolism: a population-based study in Canada. J Obstet Gynaecol Can 2009;31:611–620.
8.
Simpson EL, Lawrenson RA, Nightingale AL, Farmer RD: Venous thromboembolism in pregnancy and the puerperium: incidence and additional risk factors from a London perinatal database. BJOG 2001;108:56–60.
9.
Department of Health: Why Mothers Die. Report on Confidential Enquiries into Maternal Deaths in the United Kingdom 1994–1996. London, Department of Health, 1998.
10.
Sharma S, Monga D: Venous thromboembolism during pregnancy and the post-partum period: incidence and risk factors in a large Victorian health service. Aust NZ J Obstet Gynaecol 2008;48:44–49.
11.
Bai C, Pan J, Fan L: A study on the deficiency of anticoagulant proteins in Chinese patients with deep venous thrombosis. Zhonghua Nei Ke Za Zhi 2000;39:746–748.
12.
Shen MC, Lin JS, Tsay W: High prevalence of antithrombin III, protein C and protein S deficiency, but no factor V Leiden mutation in venous thrombophilic Chinese patients in Taiwan. Thromb Res 1997;87:377–385.
13.
Liu HW, Kwong YL, Bourke C, Lam CK, Lie AK, Wei D, Chan LC: High incidence of thrombophilia detected in Chinese patients with venous thrombosis. Thromb Haemost 1994;71:416–419.
14.
Shen MC, Lin JS, Tsay W: Protein C and protein S deficiencies are the most important risk factors associated with thrombosis in Chinese venous thrombophilic patients in Taiwan. Thromb Res 2000;99:447–452.
15.
Chen TY, Su WC, Tsao CJ: Incidence of thrombophilia detected in southern Taiwanese patients with venous thrombosis. Ann Hematol 2003;82:114–117.
16.
Rees DC, Cox M, Clegg JB: World distribution of factor V Leiden. Lancet 1995;346:1133–1134.
17.
Ko YL, Hsu TS, Wu SM, Ko YS, Chang CJ, Wang SM, Chen WJ, Cheng NJ, Kuo CT, Chiang CW, Lee YS: The G1691A mutation of the coagulation factor V gene (factor V Leiden) is rare in Chinese: an analysis of 618 individuals. Hum Genet 1996;98:176–177.
18.
Lim LC, Tan HH, Lee LH, Tien SL, Abdul Ghafar A: Activated protein C resistance: a study among 60 thromboembolic patients in the Singapore population. Ann Acad Med Singapore 1999;28:252–255.
19.
Chan WP, Lee CK, Kwong YL, Lam CK, Liang R: A novel mutation of Arg306 of factor V gene in Hong Kong Chinese. Blood 1998;91:1135–1139.
20.
Gerhardt A, Scharf RE, Beckmann MW, Struve S, Bender HG, Pillny M, Sandmann W, Zotz RB: Prothrombin and factor V mutations in women with a history of thrombosis during pregnancy and the puerperium. N Engl J Med 2000;342:374–380.
21.
McColl MD, Ellison J, Reid F, Tait RC, Walker ID, Greer IA: Prothrombin 20210G→A, MTHFR C677T mutations in women with venous thromboembolism associated with pregnancy. BJOG 2000;107:565–569.
22.
Lin JS, Shen MC, Tsay W: The mutation at position 20210 in the 3′-untranslated region of the prothrombin gene is extremely rare in Taiwanese Chinese patients with venous thrombophilia. Thromb Haemost 1998;80:343.
23.
Poort SR, Rosendaal FR, Reitsma PH, Bertina RM: A common genetic variation in the 3′-untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and an increase in venous thrombosis. Blood 1996;88:3698–3703.
24.
Chan DK, Hu G, Tao H, Owens D, Vun CM, Woo J, Chong BH: A comparison of polymorphism in the 3′-untranslated region of the prothrombin gene between Chinese and Caucasians in Australia. Br J Haematol 2000;111:1253–1255.
25.
Lu Y, Zhao Y, Liu G, Wang X, Liu Z, Chen B, Hui R: Factor V gene G1691A mutation, prothrombin gene G20210A mutation, and MTHFR gene C677T mutation are not risk factors for pulmonary thromboembolism in Chinese population. Thromb Res 2002;106:7–12.
26.
Bai C, Pan J, Li X: Factor V Leiden and PTG20210A gene mutation in patients with venous thrombosis and healthy blood donors. Zhonghua Yi Xue Za Zhi 1999;79:900–902.
27.
Zheng YZ, Tong J, Do XP, Pu XQ, Zhou BT: Prevalence of methylenetetrahydrofolate reductase C677T and its association with arterial and venous thrombosis in the Chinese population. Br J Haematol 2000;109:870–874.
28.
Den Heijer M, Rosendaal FR, Blom HJ, Gerrits WB, Bos GM: Hyperhomocysteinemia and venous thrombosis: a meta-analysis. Thromb Haemost 1998;80:874–877.
29.
Hsu TS, Hsu LA, Chang CJ, Sun CF, Ko YL, Kuo CT, Chiang CW, Lee YS: Importance of hyperhomocysteinemia as a risk factor for venous thromboembolism in a Taiwanese population. A case-control study. Thromb Res 2001;102:387–395.
30.
Zöller B, Hillarp A, Berntorp E, Dahlbäck B: Activated protein C resistance due to a common factor V gene mutation is a major risk factor for venous thrombosis. Annu Rev Med 1997;48:45–58.
31.
Ho CH, Chau WK, Hsu HC, Gau JP, Chih CM: Prevalence of factor V Leiden in the Chinese population. Zhonghua Yi Xue Za Zhi 1999;62:875–878.
32.
Ho CH, Chau WK, Hsu HC, Gau JP, Yu TJ: Causes of venous thrombosis in fifty Chinese patients. Am J Hematol 2000;63:74–78.
33.
Cattaneo M, Tsai MY, Bucciarelli P, Taioli E, Zighetti ML, Bignell M, Mannucci PM: A common mutation in the methylenetetrahydrofolate reductase gene (C677T) increases the risk for deep-vein thrombosis in patients with mutant factor V (factor V: Q506). Arterioscler Thromb Vasc Biol 1997;17:1662–1666.
34.
Lin JS, Shen MC, Tsai W, Lin B: The prevalence of C677T mutation in the methylenetetrahydrofolate reductase gene and its association with venous thrombophilia in Taiwanese Chinese. Thromb Res 2000,97:89–94.
35.
Lin JS, Shen MC, Cheng WC, Tsay W, Wang YC, Lin BB, Hung MH: Age, sex and vitamin status affect plasma level of homocysteine, but hyperhomocysteinaemia is possibly not an important risk factor for venous thrombophilia in Taiwanese Chinese. Br J Haematol 2002;117:159–163.
36.
Meglic L, Stegnar M, Milanez T, Bozic M, Peterlin B, Peternel P, Novak-Antolic Z: Factor V Leiden, prothrombin 20210G→A, methylenetetrahydrofolate reductase 677C→T and plasminogen activator inhibitor 4G/5G polymorphism in women with pregnancy-related venous thromboembolism. Eur J Obstet Gynecol Reprod Biol 2003;111:157–163.
37.
Powers RW, Dunbar MS, Gallaher MJ, Roberts JM: The 677C→T methylenetetrahydrofolate reductase mutation does not predict increased maternal homocysteine during pregnancy. Obstet Gynecol 2003;101:762–766.
38.
Den Heijer M, Willems HP, Blom HJ, Gerrits WB, Cattaneo M, Eichinger S, Rosendaal FR, Bos GM: Homocysteine lowering by B vitamins and the secondary prevention of deep vein thrombosis and pulmonary embolism: a randomized, placebo-controlled, double-blind trial. Blood 2007;109:139–144.
39.
Ray JG, Kearon C, Yi Q, Sheridan P, Lonn E: Homocysteine-lowering therapy and risk for venous thromboembolism: a randomized trial. Ann Intern Med 2007;146:761–767.
40.
Vora S, Ghosh K, Shetty S, Salvi V, Satoskar P: Deep venous thrombosis in the antenatal period in a large cohort of pregnancies from western India. Thromb J 2007;5:9.
41.
Coulam CB, Wallis D, Weinstein J, DasGupta DS, Jeyendran RS: Comparison of thrombophilic gene mutations among patients experiencing recurrent miscarriage and deep vein thrombosis. Am J Reprod Immunol 2008;60:426–431.
42.
Bezemer ID, Bare LA, Doggen CJ, Arellano AR, Tong C, Rowland CM, Catanese J, Young BA, Reitsma PH, Devlin JJ, Rosendaal FR: Gene variants associated with deep vein thrombosis. JAMA 2008;299:1306–1314.
43.
Morange PE, Bezemer I, Saut N, Bare L, Burgos G, Brocheton J, Durand H, Biron-Andreani C, Schved JF, Pernod G, Galan P, Drouet L, Zelenika D, Germain M, Nicaud V, Heath S, Ninio E, Delluc A, Münzel T, Zeller T, Brand-Herrmann SM, Alessi MC, Tiret L, Lathrop M, Cambien F, Blankenberg S, Emmerich J, Trégouët DA, Rosendaal FR: A follow-up study of a genome-wide association scan identifies a susceptibility locus for venous thrombosis on chromosome 6p24.1. Am J Hum Genet 2010;86:592–595.
44.
Smith NL, Rice KM, Bovill EG, Cushman M, Bis JC, McKnight B, Lumley T, Glazer NL, van Hylckama Vlieg A, Tang W, Dehghan A, Strachan DP, O’Donnell CJ, Rotter JI, Heckbert SR, Psaty BM, Rosendaal FR: Genetic variation associated with plasma von Willebrand factor levels and the risk of incident venous thrombosis. Blood 2011;117:6007–6011.
45.
Morange PE, Oudot-Mellakh T, Cohen W, Germain M, Saut N, Antoni G, Alessi MC, Bertrand M, Dupuy AM, Letenneur L, Lathrop M, Lopez LM, Lambert JC, Emmerich J, Amouyel P, Trégouët DA: KNG1 Ile581Thr and susceptibility to venous thrombosis. Blood 2011;117:3692–3694.
46.
Miyata T, Kimura R, Kokubo Y, Sakata T: Genetic risk factors for deep vein thrombosis among Japanese: importance of protein S K196E mutation. Int J Hematol 2006;83:217–223.
47.
Yin T, Takeshita S, Sato Y, Sakata T, Shin Y, Honda S, Kawasaki T, Tsuji H, Kojima T, Madoiwa S, Sakata Y, Murata M, Ikeda Y, Miyata T: A large deletion of the PROS1 gene in a deep vein thrombosis patient with protein S deficiency. Thromb Haemost 2007;98:783–789.
48.
Miyata T, Sato Y, Ishikawa J, Okada H, Takeshita S, Sakata T, Kokame K, Kimura R, Honda S, Kawasaki T, Suehisa E, Tsuji H, Madoiwa S, Sakata Y, Kojima T, Murata M, Ikeda Y: Prevalence of genetic mutations in protein S, protein C and antithrombin genes in Japanese patients with deep vein thrombosis. Thromb Res 2009;124:14–18.
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