Skip to main content Accessibility help

We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.

Close cookie message
×
Hostname: page-component-745bb68f8f-d8cs5 Total loading time: 0 Render date: 2025-02-07T10:03:56.986Z Has data issue: false hasContentIssue false

21 - Thrombophilias and pre-eclampsia

from Part II - Clinical Practice

Published online by Cambridge University Press:  03 September 2009

By
Isobel D. Walker
Edited by
Fiona Lyall  and
Michael Belfort
Fiona Lyall
Affiliation:
University of Glasgow
Michael Belfort
Affiliation:
University of Utah
Get access

Summary

Introduction

Pre-eclampsia remains a leading cause of maternal and fetal morbidity and mortality. It is a pregnancy-specific multisystem disorder, occurring most commonly in primigravidae and characterized by the development of hypertension and proteinuria in the second half of pregnancy. The incidence in a second pregnancy is less than 1% in women who have had a normotensive first pregnancy, but is increased in women who have had pre-eclampsia in their first pregnancy, particularly in women whose first pregnancy was complicated by severe pre-eclampsia (Campbell et al., 1985). This issue is more completely discussed in the chapter by Dekker and Robillard in this book. The pathogenesis of pre-eclampsia is not fully understood but it is believed that genetic predisposition and immune maladaptation lead to placental ischemia and perturbation of the maternal vascular endothelium. Coagulation activation is an important feature and hypercoagulable states, including both inherited and acquired thrombophilias, have been associated not only with pregnancy thromboembolism but also with other adverse pregnancy events.

Normal hemostasis

The primary initiator of coagulation is tissue factor. Tissue factor (TF) is expressed by epithelial, stromal and perivascular cells throughout the body but not normally by cells in contact with the circulation. Following vascular damage, membrane-bound TF complexes with factor VII (FVII). Cleavage of FVII results in the formation of activated FVIIa. Thereafter TF–FVIIa complex can directly activate factor X (FX). TF–FVIIa complex may also activate FX indirectly via activation of factor IX (FIX).

Type
Chapter
Information
Pre-eclampsia
Etiology and Clinical Practice
 , pp. 305 - 324
Publisher: Cambridge University Press
Print publication year: 2007

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Bertina, R. M., Koeleman, B. P. C., Koster, T., et al. (1994). Mutation in blood coagulation factor V associated with resistance to activated protein C. Nature, 369(6475), 64–7.CrossRefGoogle ScholarPubMed
Bombeli, T., Mueller, M. and Haeberli, A. (1997). Anticoagulant properties of the vascular endothelium. Thromb. Haem., 77(3), 408–23.Google ScholarPubMed
Borg, A. J., Higgins, J. R., Brennecke, S. P. and Moses, E. K. (2002). Thrombomodulin Ala455Val dimorphism is not associated with pre-eclampsia in Australian and New Zealand women. Gynecol. Obstet. Invest., 54(1), 43–5.CrossRefGoogle Scholar
Branch, D. W., Andres, R., Digre, K. B., Rote, N. S. and Scott, J. R. (1989). The association of antiphospholipid antibodies with severe preeclampsia. Obstet. Gynecol., 73(4), 541–5.Google ScholarPubMed
Branch, D. W., Silver, R., Pierangeli, S., Van, L., and Harris, E. N. (1997). Antiphospholipid antibodies other than lupus anticoagulant and anticardiolipin antibodies in women with recurrent pregnancy loss, fertile controls, and antiphospholipid syndrome. Obstet. Gynecol., 89(4), 549–55.Google ScholarPubMed
Bremme, K., Ostlund, E., Almqvist, I., Heinonen, K. and Blomback, M. (1992). Enhanced thrombin generation and fibrinolytic activity in normal pregnancy and the puerperium. Obstet. Gynecol., 80(1), 132–7.Google ScholarPubMed
Cadroy, Y., Grandjean, H., Pichon, J., et al. (1993). Evaluation of six markers of haemostatic system in normal pregnancy and pregnancy complicated by hypertension or pre-eclampsia. Br. J. Obstet. Gynaecol., 100(5), 416–20.CrossRefGoogle ScholarPubMed
Campbell, D. M., MacGillivray, I. and Carr-Hill, R. (1985). Pre-eclampsia in second pregnancy. Br. J. Obstet. Gynaecol., 92(2), 131–40.CrossRefGoogle ScholarPubMed
Clark, P. (2003). Changes of haemostasis variables during pregnancy. Semi. Vasc. Med., 3, 13–24.CrossRefGoogle ScholarPubMed
Clark, P., Brennand, J., Conkie, J. A., McCall, F., Greer, I. A. and Walker, I. D. (1998). Activated protein C sensitivity, protein C, protein S and coagulation in normal pregnancy. Thromb. Haem., 79(6), 166–70.Google ScholarPubMed
Clark, P., Sattar, N., Walker, I. D. and Greer, I. A. (2001). The Glasgow Outcome, APCR and Lipid (GOAL) pregnancy study: significance of pregnancy associated activated protein C resistance. Thromb. Haem., 85(1), 30–5.Google ScholarPubMed
Comeglio, P., Fedi, S., Liotta, A. A., et al. (1996). Blood clotting activation during normal pregnancy. Thromb. Res., 84(3), 199–202.CrossRefGoogle ScholarPubMed
Creagh, M. D., Malia, R. G., Cooper, S. M., Smith, A. R., Duncan, S. L. B. and Greaves, M. (1991). Screening for lupus anticoagulant and anticardiolipin antibodies in women with fetal loss. J. Clin. Pathol., 44(1), 45–7.CrossRefGoogle ScholarPubMed
Cumming, A. M., Tait, R. C., Fildes, S., Yoong, A., Keeney, S. and Hay, C. R. M. (1995). Development of resistance to activated protein C during pregnancy. Br. J. Haematol., 90(3), 725–7.CrossRefGoogle ScholarPubMed
Dahlback, B., Carlsson, M. and Svensson, P. J. (1993). Familial thrombophilia due to a previously unrecognized mechanism characterized by poor anticoagulant response to activated protein C: prediction of a cofactor to activated protein C. Proc. Natl Acad. Sci. USA, 90(3), 1004–8.CrossRefGoogle ScholarPubMed
Groot, C. J. M., Bloemenkamp, K. W. M., Duvekot, E. J., et al. (1999). Preeclampsia and genetic risk factors for thrombosis: a case-control study. Am. J. Obstet. Gynecol., 181(4), 975–80.CrossRefGoogle ScholarPubMed
Dekker, G. A., Vries, J. I. P., Doelitzsch, P. M., et al. (1995). Underlying disorders associated with severe early-onset preeclampsia. Am. J. Obstet. Gynecol., 173(4), 1042–8.CrossRefGoogle ScholarPubMed
Visser, M. C. H., Rosendaal, F. R. and Bertina, R. M. (1999). A reduced sensitivity for activated protein C in the absence of factor V Leiden increases the risk of venous thrombosis. Blood, 93(4), 1271–6.Google ScholarPubMed
Dizon-Townson, D. S., Meline, L., Nelson, L. M., Varner, M. and Ward, K. (1997). Fetal carriers of the factor V Leiden mutation are prone to miscarriage and placental infarction. Am. J. Obstet. Gynecol., 177(2), 402–5.CrossRefGoogle ScholarPubMed
Dizon-Townson, D. S., Nelson, L. M., Easton, K. and Ward, K. (1996). The factor V Leiden mutation may predispose women to severe preeclampsia. Am. J. Obstet. Gynecol., 175(4), 902–5.CrossRefGoogle ScholarPubMed
Dykes, A. C., Walker, I. D., McMahon, A. D., Islam, S. I. A. M. and Tait, R. C. (2001). A study of Protein S antigen levels in 3788 healthy volunteers: influence of age, sex and hormone use, and estimate for prevalence of deficiency state. Br. J. Haematol., 113(3), 636–41.CrossRefGoogle ScholarPubMed
Esmon, C. T., Esmon, N. L. and Harris, K. W. (1982). Complex formation between thrombin and thrombomodulin inhibits both thrombin-catalyzed fibrin formation and factor V activation. J. Biol. Chem., 257(14), 7944–7.Google ScholarPubMed
Esmon, C. T. and Owen, W. G. (1981b). Identification of an endothelial cell cofactor for thrombin-catalyzed activation of protein C. Proc. Natl Acad. Sci. USA, 78(4), 2249–52.CrossRefGoogle Scholar
Esmon, C. T. and Owen, W. G. (1981a). Identification of an endothelial cell cofactor for thrombin-catalyzed activation of protein C. Proc. Natl Acad. Sci. USA, 78(4), 2249–52.CrossRefGoogle Scholar
Esmon, N. L., Carroll, R. C. and Esmon, C. T. (1983). Thrombomodulin blocks the ability of thrombin to activate platelets. J. Biol. Chem., 258(20), 12,238–42.Google ScholarPubMed
Faioni, E. M., Valsecchi, C., Palla, A., Taioli, E., Razzari, C. and Mannucci, P. M. (1997). Free protein S deficiency is a risk factor for venous thrombosis. Thromb. Haem., 78(5), 1343–6.Google ScholarPubMed
Fernandez, J. A., Estelles, A., Gilabert, J., Espana, F. and Aznar, J. (1989). Functional and immunologic protein S in normal pregnant women and in full-term newborns. Thromb. Haem., 61(3), 474–8.Google ScholarPubMed
Finazzi, G., Brancaccio, V., Moia, M., et al. (1996). Natural history and risk factors for thrombosis in 360 patients with antiphospholipid antibodies: a four-year prospective study from the Italian registry. Am. J. Med., 100(5), 530–6.CrossRefGoogle ScholarPubMed
Ginsberg, J. S., Brill-Edwards, P., Johnston, M., et al. (1992). Relationship of antiphospholipid antibodies to pregnancy loss in patients with systemic lupus erythematosus: a cross-sectional study. Blood, 80(4), 975–80.Google ScholarPubMed
Grandone, E., Margaglione, M., Colaizzo, D., et al. (1997). Factor V leiden, C > T MTHFR polymorphism and genetic susceptibility to preeclampsia. Thromb. Haem., 77(6), 1052–4.Google Scholar
Grandone, E., Margaglione, M., Colaizzo, D., et al. (1999). Prothrombotic genetic risk factors and the occurrence of gestational hypertension with or without proteinuria. Thromb. Haem., 81(3), 349–52.Google ScholarPubMed
Greaves, M., Cohen, H., Machin, S. J. and Mackie, I. (2000). Guidelines on the investigation and management of the antiphospholipid syndrome. Br. J. Haematol., 109(4), 704–15.CrossRefGoogle ScholarPubMed
Haverkate, F. and Samama, M. (1995). Familial dysfibrinogenemia and thrombophilia – report on a study of the SSC subcommittee on fibrinogen. Thromb. Haem., 73(1), 151–61.Google ScholarPubMed
Higgins, J. R., Kaiser, T., Moses, E. K., North, R. and Brennecke, S. P. (2000). Prothrombin G20210A mutation: is it associated with pre-eclampsia?Gynecol. Obstet. Invest., 50(4), 254–7.CrossRefGoogle ScholarPubMed
Hira, B., Pegoraro, R. J., Rom, L. and Moodley, J. (2003). Absence of Factor V Leiden, thrombomodulin and prothrombin gene variants in Black South African women with pre-eclampsia and eclampsia. Br. J. Obstet. Gynaecol., 110(3), 327–8.CrossRefGoogle ScholarPubMed
Infante-Rivard, C., David, M., Gauthier, R. and Rivard, G.-E. (1991). Lupus anticoagulants, anticardiolipin antibodies, and fetal loss: a case-control study. N. Engl. J. Med., 325(15), 1063–6.CrossRefGoogle ScholarPubMed
Kaiser, T., Brennecke, S. P. and Moses, E. K. (2000). Methylenetetrahydrofolate reductase polymorphisms are not a risk factor for pre-eclampsia/eclampsia in Australian women. Gynecol. Obstet. Invest., 50(2), 100–2.CrossRefGoogle Scholar
Kaiser, T., Brennecke, S. P. and Moses, E. K. (2001). C677T methylenetetrahydrofolate reductase polymorphism is not a risk factor for pre-eclampsia/eclampsia among Australian women. Hum. Hered., 51(1–2), 20–2.CrossRefGoogle Scholar
Kjellberg, U., Andersson, N.-E., Rosen, S., Tengborn, L. and Hellgren, M. (1999). APC resistance and other haemostatic variables during pregnancy and puerperium. Thromb. Haem., 81(4), 527–31.Google ScholarPubMed
Knight, M., Redman, C. W. G., Linton, E. A. and Sargent, I. L. (1998). Shedding of syncytiotrophoblast microvilli into the maternal circulation in pre-eclamptic pregnancies. Br. J. Obstet. Gynaecol., 105(6), 632–40.CrossRefGoogle ScholarPubMed
Kobashi, G., Yamada, H., Asano, T., et al. (1999). The factor V Leiden mutation is not a common cause of pregnancy induced hypertension in Japan. Semin. Thromb. Hem., 25, 487–9.CrossRefGoogle Scholar
Kobashi, G., Yamada, H., Asano, T., et al. (2000). Absence of association between a common mutation in the methylenetetrahydrofolate reductase gene and preeclampsia in Japanese women. Am. J. Med. Genetics, 93(2), 122–5.3.0.CO;2-Z>CrossRefGoogle ScholarPubMed
Koster, T., Blann, A. D., Briet, E., Vandenbroucke, J. P. and Rosendaal, F. R. (1995). Role of clotting factor VIII in effect of von Willebrand factor on occurrence of deep-vein thrombosis. Lancet, 345(8943), 152–5.CrossRefGoogle ScholarPubMed
Kraaijenhagen, R. A., In't Anker, P. S., Koopman, M. M. W., et al. (2000). High plasma concentration of factor VIIIc is a major risk factor for venous thromboembolism. Thromb. Haem., 83(1), 5–9.Google ScholarPubMed
Kupferminc, M. J., Eldor, A., Steinman, N., et al. (1999). Increased frequency of genetic thrombophilia in women with complications of pregnancy. N. Engl. J. Med., 340(1), 9–13.CrossRefGoogle ScholarPubMed
Kupferminc, M. J., Fait, G., Many, A., Gordon, D., Eldor, A. and Lessing, J. B. (2000a). Severe preeclampsia and high frequency of genetic thrombophilic mutations. Obstet. Gynecol., 96(1), 45–9.Google Scholar
Kupferminc, M. J., Peri, H., Zwang, E., Yaron, Y., Wolman, I. and Eldor, A. (2000b). High prevalence of the prothrombin gene mutation in women with intrauterine growth retardation, abruptio placentae and second trimester loss. Acta Obstet. Gynecol. Scand., 79(11), 963–7.Google Scholar
Lachmeijer, A. M. A., Arngrimsson, R., Bastiaans, E. J., et al. (2001). Mutations in the gene for methylenetetrahydrofolate reductase, homocysteine levels, and vitamin status in women with a history of preeclampsia. Am. J. Obstet. Gynecol., 184(3), 394–402.CrossRefGoogle ScholarPubMed
Laivuori, H., Kaaja, R., Ylikorkala, O., Hiltunen, T. and Kontula, K. (2000). 677 C right arrow T polymorphism of the methylenetetrahydrofolate reductase gene and preeclampsia. Obstet. Gynecol., 96(2), 277–80.Google Scholar
Lindoff, C., Ingemarsson, I., Martinsson, G., Segelmark, M., Thysell, H. and Astedt, B. (1997). Preeclampsia is associated with a reduced response to activated protein C. Am. J. Obstet. Gynecol., 176(2), 457–60.CrossRefGoogle ScholarPubMed
Lindqvist, P. G., Svensson, P. J., Dahlback, B. and Marsal, K. (1998). Factor V Q506 mutation (activated protein C resistance) associated with reduced intrapartum blood loss – a possible evolutionary selection mechanism. Thromb. Haem., 79(1), 69–73.Google ScholarPubMed
Lindqvist, P. G., Svensson, P. J., Marsal, K., Grennert, L., Luterkor, M., and Dahlback, B. (1999). Activated protein C resistance (FV:Q506) and pregnancy. Thromb. Haem., 81(4), 532–7.Google Scholar
Livingston, J. C., Barton, J. R., Park, V., Haddad, B., Phillips, O. and Sibai, B. M. (2001). Maternal and fetal inherited thrombophilias are not related to the development of severe preeclampsia. Am. J. Obstet. Gynecol., 185(1), 153–7.CrossRefGoogle Scholar
Long, A. A., Ginsberg, J. S., Brill-Edwards, P., et al. (1991). The relationship of antiphospholipid antibodies to thromboembolic disease in systemic lupus erythematosus: a cross-sectional study. Thromb. Haem., 66(5), 520–4.Google ScholarPubMed
Love, P. E. and Santoro, S. A. (1990). Antiphospholipid antibodies: anticardiolipin and the lupus anticoagulant in systemic lupus erythematosus (SLE) and in non-SLE disorders. Prevalence and clinical significance. Ann. Int. Med., 112(9), 682–98.CrossRefGoogle ScholarPubMed
Lynch, A., Marlar, R., Murphy, J., et al. (1994). Antiphospholipid antibodies in predicting adverse pregnancy outcome: a prospective study. Ann. Int. Med., 120(6), 470–5.CrossRefGoogle ScholarPubMed
Malm, J., Laurell, M. and Dahlback, B. (1988). Changes in the plasma levels of vitamin K-dependent proteins C and S and of C4b-binding protein during pregnancy and oral contraception. Br. J. Haematol., 68(4), 437–43.CrossRefGoogle Scholar
Maruyama, I., Bell, C. E. and Majerus, P. W. (1985). Thrombomodulin is found on endothelium of arteries, veins, capillaries, and lymphatics, and on syncytiotrophoblast of human placenta. J. Cell Biol., 101(2), 363–71.CrossRefGoogle ScholarPubMed
Mateo, J., Oliver, A., Borrell, M., Sala, N. and Fontcuberta, J. (1997). Laboratory evaluation and clinical characteristics of 2,132 consecutive unselected patients with venous thromboembolism – results of the Spanish multicentric study on thrombophilia (EMET-Study). Thromb. Haem., 77(3), 444–51.Google Scholar
Mathonnet, F., Mazancourt, P., Bastenaire, B., et al. (1996). Activated protein C sensitivity ratio in pregnant women at delivery. Br. J. Haematol., 92(1), 244–6.CrossRefGoogle ScholarPubMed
Meekins, J. W., Pijnenborg, R., Hanssens, M., McFadyen, I. R. and Asshe, A. (1994). A study of placental bed spiral arteries and trophoblast invasion in normal and severe pre-eclamptic pregnancies. Br. J. Obstet. Gynaecol., 101(8), 669–74.CrossRefGoogle ScholarPubMed
Mimuro, S., Lahoud, R., Beutler, L. and Trudinger, B. (1998). Changes of resistance to activated protein C in the course of pregnancy and prevalence of factor V mutation. Austr. N. Z. J. Obstet. Gynaecol., 38(2), 200–4.CrossRefGoogle ScholarPubMed
Morrison, E. R., Miedzybrodzka, Z. H., Campbell, D. M., et al. (2002). Prothrombotic genotypes are not associated with pre-eclampsia and gestational hypertension: results from a large population-based study and systematic review. Thromb. Haem., 87(5), 779–85.CrossRefGoogle Scholar
Murphy, R. P., Donoghue, C., Nallen, R. J., D'Mello, M., Regan, C., Whitehead, A. S. and Fitzgerald, D. J. (2000). Prospective evaluation of the risk conferred by factor V Leiden and thermolabile methylenetetrahydrofolate reductase polymorphisms in pregnancy. Arterioscler. Thromb. Vasc. Biol., 20(1), 266–70.CrossRefGoogle ScholarPubMed
Nagy, B., Toth, T., Rigo, J. Jr., Karadi, I., Romics, L. and Papp, Z. (1998). Detection of factor V Leiden mutation in severe pre-eclamptic Hungarian women. Clin. Genet., 53(6), 478–81.CrossRefGoogle ScholarPubMed
Nakabayashi, M., Yamamoto, S. and Suzuki, K. (1999). Analysis of thrombomodulin gene polymorphism in women with severe early-onset preeclampsia. Semin. Thromb. Hem., 25(5), 473–9.CrossRefGoogle ScholarPubMed
Novotny, W. F., Brown, S. G., Miletich, J. P., Rader, D.J., and Broze, G. J. Jr. (1991). Plasma antigen levels of the lipoprotein-associated coagulation inhibitor in patient samples. Blood, 78(2), 387–93.Google ScholarPubMed
O'Shaughnessy, K. M., Fu, B., Ferraro, F., Lewis, I., Downing, S. and Morris, N. H. (1999). Factor V Leiden and thermolabile methylenetetrahydrofolate reductase gene variants in an East Anglian preeclampsia cohort. Hypertension, 33(6), 1338–41.CrossRefGoogle Scholar
Out, H. J., Bruinse, H. W., Christiaens, G. C. M. L., et al. (1992). A prospective, controlled multicenter study on the obstetric risks of pregnant women with antiphospholipid antibodies. Am. J. Obstet. Gynecol., 167(1), 26–32.CrossRefGoogle ScholarPubMed
Out, H. J., Bruinse, H. W., Christiaens, G. C. M. L., et al. (1991). Prevalence of antiphospholipid antibodies in patients wih fetal loss. Ann. Rheum. Dis., 50(8), 553–7.CrossRefGoogle Scholar
Pabinger, I., Grafenhofer, H., Kaider, A., et al. (2001). Preeclampsia and fetal loss in women with a history of venous thromboembolism. Arterioscler. Thromb. Vasc. Biol., 21(5), 874–9.CrossRefGoogle ScholarPubMed
Parazzini, F., Acaia, B., Faden, D., Lovotti, M., Marelli, G. and Cortelazzo, S. (1991). Antiphospholipid antibodies and recurrent abortion. Obstet. Gynecol., 77(6), 854–8.Google ScholarPubMed
Poort, S. R., Rosendaal, F. R., Reitsma, P. H. and Bertina, R. M. (1996). 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, 88(10), 3698–703.Google ScholarPubMed
Powers, R. W., Minich, L. A., Lykins, D. L., et al. (1999). Methylenetetrahydrofolate reductase polymorphism, folate, and susceptibility to preeclampsia. J. Soc. Gynecol. Invest., 6(2), 74–9.CrossRefGoogle ScholarPubMed
Rajah, S. B., Moodley, J., Pudifin, D. and Duursma, J. (1990). Anticardiolipin antibodies in hypertensive emergencies in pregnancy. Clin. Exp. Hypertens. Part B, Hypertens. Pregn., 9(3), 267–71.CrossRefGoogle Scholar
Rand, J. H., Wu, X.-X., Andree, H. A. M., et al. (1997). Pregnancy loss in the antiphospholipid-antibody syndrome – a possible thrombogenic mechanism. N. Engl. J. Med., 337(3), 154–60.CrossRefGoogle ScholarPubMed
Redman, C. W. G. and Sargent, I. L. (2000). Placental debris, oxidative stress and pre-eclampsia. Placenta, 21(7), 597–602.CrossRefGoogle ScholarPubMed
Rees, D. C., Cox, M. and Clegg, J. B. (1995). World distribution of factor V Leiden. Lancet, 346(8983), 1133–4.CrossRefGoogle ScholarPubMed
Ridker, P. M., Miletich, J. P., Hennekens, C. H. and Buring, J. E. (1997). Ethnic distribution of factor V Leiden in 4047 men and women: implications for venous thromboembolism screening. J. Am. Med. Ass., 277(16), 1305–7.CrossRefGoogle ScholarPubMed
Rigo, J. Jr., Nagy, B., Fintor, L., Tanyi, J., Beke, A., Karadi, I. and Papp, Z. (2000). Maternal and neonatal outcome of preeclamptic pregnancies: the potential roles of Factor V Leiden mutation and 5,10 methylenetetrahydrofolate reductase. Hypertens. Pregn., 19(2), 163–72.CrossRefGoogle ScholarPubMed
Rigo, J. J., Nagy, B., Fintor, L., et al. (2002). Factor V Leiden mutation and preeclampsia 6 (multiple letters). Am. J. Obstet. Gynecol., 186(4), 853–4.CrossRefGoogle Scholar
Rosendaal, F. R. (1999a). Risk factors for venous thrombotic disease. Thromb. Haem., 82(2), 610–19.Google Scholar
Rosendaal, F. R. (1999b). Venous thrombosis: a multicausal disease. Lancet, 353(9159), 1167–73.CrossRefGoogle Scholar
Rosendaal, F. R., Koster, T., Vandenbroucke, J. P. and Reitsma, P. H. (1995). High risk of thrombosis in patients homozygous for factor V Leiden (activated protein C resistance). Blood, 85(6), 1504–8.Google Scholar
Simioni, P., Prandoni, P., Zanon, E., et al. (1996). Deep venous thrombosis and lupus anticoagulant. A case-control study. Thromb. Haem., 76(2), 187–9.Google ScholarPubMed
Sohda, S., Arinami, T., Hamada, H., Yamada, N., Hamaguchi, H. and Kubo, T. (1997). Methylenetetrahydrofolate reductase polymorphism and pre-eclampsia. J. Med. Genet., 34(6), 525–6.CrossRefGoogle ScholarPubMed
Souto, J. C., Coll, I., Llobet, D., et al. (1998). The prothrombin 20210A allele is the most prevalent genetic risk factor for venous thromboembolism in the Spanish population. Thromb. Haem., 80(3), 366–9.Google ScholarPubMed
Tait, R. C., Walker, I. D., Perry, D. J., et al. (1994). Prevalence of antithrombin deficiency in the healthy population. Br. J. Haematol., 87(1), 106–12.CrossRefGoogle ScholarPubMed
Tait, R. C., Walker, I. D., Reitsma, P. H., et al. (1995). Prevalence of protein C deficiency in the healthy population. Thromb. Haem., 73(1), 87–93.Google ScholarPubMed
Pampus, M. G., Dekker, G. A., Wolf, H., et al. (1999). High prevalence of hemostatic abnormalities in women with a history of severe preeclampsia. Am. J. Obstet. Gynecol., 180(5), 1146–50.CrossRefGoogle ScholarPubMed
Tempelhoff, G.-F., Heilmann, L., Spanuth, E., Kunzmann, E. and Hommel, G. (2000). Incidence of the Factor V Leiden-mutation, coagulation inhibitor deficiency, and elevated antiphospholipid-antibodies in patients with preeclampsia or HELLP-Syndrome. Thromb. Res., 100(4), 363–5.CrossRefGoogle Scholar
Yasuda, M., Takakuwa, K., Tokunaga, A. and Tanaka, K. (1995). Prospective studies of the association between anticardiolipin antibody and outcome of pregnancy. Obstet. Gynecol., 86(4), 555–9.CrossRefGoogle ScholarPubMed
Young, J. K., Williamson, R. A., Murray, J. C., et al. (2001). Genetic susceptibility to preeclampsia: roles of cytosine-to-thymine substitution at nucleotide 677 of the gene for methylenetetrahydrofolate reductase, 68-base pair insertion at nucleotide 844 of the gene for cystathionine beta-synthase, and factor V Leiden mutation. Am. J. Obstet. Gynecol., 184(6), 1211–17.Google Scholar
Zusterzeel, P. L. M., Visser, W., Blom, H. J., Peters, W. H. M., Heil, S. G. and Steegers, E. A. P. (2000). Methylenetetrahydrofolate reductase polymorphisms in preeclampsia and the HELLP syndrome. Hypertens. Pregn., 19(3), 299–307.CrossRefGoogle ScholarPubMed

Save book to Kindle

To save this book to your Kindle, first ensure no-reply@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Available formats
×

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

Available formats
×