Thrombophilia and Pre-Eclampsia

ABSTRACT

Pre-eclampsia (P-EC) poses an increased risk for fetal and maternal morbidity and sometimes even mortality. Several risk factors have been identified, among which an important extensively studied group is formed by the early recognizable genetic factors resulting in thrombophilia. The discussion is ongoing whether the associations found for thrombophilia are true and clinically relevant. In this review, we address the association between P-EC and thrombophilia, its concerns, and the necessity of screening after a pregnancy complicated by hypertension.

KEYWORDS

Thrombophilia - pre-eclampsia - genetic variation - polymorphism

REFERENCES

• 1 Dekker G A. Blood pressure measurement in antenatal care. In: Wildschut H IJ, Weiner C P, Peters T J, eds. When to Screen in Obstetrics and Gynecology. London, United Kingdom: WB Saunders; 1996: 154-162
• 2 Murphy D J, Stirrat G M. Mortality and morbidity associated with early-onset preeclampsia.  Hypertens Pregnancy. 2000;  19 (2) 221-231
• 3 Schutte J M, Schuitemaker N W, van Roosmalen J, Steegers E A, Dutch Maternal Mortality C. Dutch Maternal Mortality Committee . Substandard care in maternal mortality due to hypertensive disease in pregnancy in the Netherlands.  BJOG. 2008;  115 (6) 732-736
• 4 Dekker G A, de Vries J I, Doelitzsch P M et al. Underlying disorders associated with severe early-onset preeclampsia.  Am J Obstet Gynecol. 1995;  173 (4) 1042-1048
• 5 Robertson L, Wu O, Langhorne P Thrombosis: Risk and Economic Assessment of Thrombophilia Screening (TREATS) Study et al. Thrombophilia in pregnancy: a systematic review.  Br J Haematol. 2006;  132 (2) 171-196
• 6 Seligsohn U, Lubetsky A. Genetic susceptibility to venous thrombosis.  N Engl J Med. 2001;  344 (16) 1222-1231
• 7 Greer I A. Thrombophilia: implications for pregnancy outcome.  Thromb Res. 2003;  109 (2-3) 73-81
• 8 Caprini J A, Glase C J, Anderson C B, Hathaway K. Laboratory markers in the diagnosis of venous thromboembolism.  Circulation. 2004;  109 (12, Suppl 1) I4-I8
• 9 Bertina R M, Reitsma P H, Rosendaal F R, Vandenbroucke J P. Resistance to activated protein C and factor V Leiden as risk factors for venous thrombosis.  Thromb Haemost. 1995;  74 (1) 449-453
• 10 Torricelli M, Sabatini L, Florio P et al. Levels of antibodies against protein C and protein S in pregnancy and in preeclampsia.  J Matern Fetal Neonatal Med. 2009;  22 (11) 993-999
• 11 Rodger M A, Paidas M, McLintock C et al. Inherited thrombophilia and pregnancy complications revisited.  Obstet Gynecol. 2008;  112 (2 Pt 1) 320-324
• 12 Sikkema J M, Franx A, Bruinse H W, van der Wijk N G, de Valk H W, Nikkels P G. Placental pathology in early onset pre-eclampsia and intra-uterine growth restriction in women with and without thrombophilia.  Placenta. 2002;  23 (4) 337-342
• 13 Kosmas I P, Tatsioni A, Ioannidis J P. Association of Leiden mutation in factor V gene with hypertension in pregnancy and pre-eclampsia: a meta-analysis.  J Hypertens. 2003;  21 (7) 1221-1228
• 14 Morrison E R, Miedzybrodzka Z H, Campbell D M et al. Prothrombotic genotypes are not associated with pre-eclampsia and gestational hypertension: results from a large population-based study and systematic review.  Thromb Haemost. 2002;  87 (5) 779-785
• 15 Lin J, August P. Genetic thrombophilias and preeclampsia: a meta-analysis.  Obstet Gynecol. 2005;  105 (1) 182-192
• 16 Mütze S, Rudnik-Schöneborn S, Zerres K, Rath W. Genes and the preeclampsia syndrome.  J Perinat Med. 2008;  36 (1) 38-58
• 17 Kahn S R, Platt R, McNamara H et al. Inherited thrombophilia and preeclampsia within a multicenter cohort: the Montreal Preeclampsia Study.  Am J Obstet Gynecol. 2009;  200 (2) 151, e1-e9 discussion e1-e5
• 18 Livingston J C, Barton J R, Park V, Haddad B, Phillips O, Sibai B M. Maternal and fetal inherited thrombophilias are not related to the development of severe preeclampsia.  Am J Obstet Gynecol. 2001;  185 (1) 153-157
• 19 Zhang Y, Hu Y, Guo T, Wei W, Zhang X. Thrombin activatable fibrinolysis inhibitor in preeclampsia and gestational hypertension throughout the gestation.  J Huazhong Univ Sci Technolog Med Sci. 2008;  28 (2) 140-143
• 20 Coolman M, de Maat M, Van Heerde W L. Matrix metalloproteinase-9 gene -1562C/T polymorphism mitigates preeclampsia.  Placenta. 2007;  28 (7) 709-713
• 21 De Maat M P, Jansen M W, Hille E T et al. Preeclampsia and its interaction with common variants in thrombophilia genes.  J Thromb Haemost. 2004;  2 (9) 1588-1593
• 22 Wiwanitkit V. Correlation between plasminogen activator inhibitor-1 4G/5G polymorphism and pre-eclampsia: an appraisal.  Arch Gynecol Obstet. 2006;  273 (6) 322-324
• 23 Greer I A. Thrombosis in pregnancy: maternal and fetal issues.  Lancet. 1999;  353 (9160) 1258-1265
• 24 Sabadell J, Casellas M, Alijotas-Reig J, Arellano-Rodrigo E, Cabero L. Inherited antithrombin deficiency and pregnancy: maternal and fetal outcomes.  Eur J Obstet Gynecol Reprod Biol. 2010;  149 (1) 47-51
• 25 van Pampus M G, Dekker G A, Wolf H et al. High prevalence of hemostatic abnormalities in women with a history of severe preeclampsia.  Am J Obstet Gynecol. 1999;  180 (5) 1146-1150
• 26 Rodger M A. Thrombophilia and placenta-mediated pregnancy complications: from the bench to bedside to policy.  Thromb Res. 2009;  123 (Suppl 2) S100-S104
• 27 Lindhoff-Last E, Luxembourg B. Evidence-based indications for thrombophilia screening.  Vasa. 2008;  37 (1) 19-30
• 28 Wu O, Robertson L, Twaddle S et al. Screening for thrombophilia in high-risk situations: systematic review and cost-effectiveness analysis. The Thrombosis: Risk and Economic Assessment of Thrombophilia Screening (TREATS) study.  Health Technol Assess. 2006;  10 (11) 1-110
• 29 Bates S M, Greer I A, Pabinger I, Sofaer S, Hirsh J. American College of Chest Physicians . Venous thromboembolism, thrombophilia, antithrombotic therapy, and pregnancy: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition).  Chest. 2008;  133 (6, Suppl) 844S-886S
• 30 Kalk J J, Huisjes A J, de Groot C J et al. Recurrence rate of pre-eclampsia in women with thrombophilia influenced by low-molecular-weight heparin treatment?.  Neth J Med. 2004;  62 (3) 83-87
• 31 Founds S A, Conley Y P, Lyons-Weiler J F, Jeyabalan A, Hogge W A, Conrad K P. Altered global gene expression in first trimester placentas of women destined to develop preeclampsia.  Placenta. 2009;  30 (1) 15-24