Abstract
Objectives
Preeclampsia complicates 2–8% of all pregnancies. Studies on the association of preeclampsia
with thrombophilia are conflicting. Clinical heterogeneity of the disease may be one
of the explanations.
The present study addresses the question whether different phenotypes of preeclampsia
are associated with thrombophilia factors.
Study design We planned a retrospective cohort study. From 1985 until 2010 women with
preeclampsia were offered postpartum screening for the following thrombophilia factors:
anti-phospholipid antibodies, APC-resistance, protein C deficiency and protein S deficiency,
hyperhomocysteineamia, factor V Leiden and Prothrombin gene mutation. Hospital records
were used to obtain information on phenotypes of the preeclampsia and placental histology.
Results
We identified 844 women with singleton pregnancies who were screened for thrombophilia
factors. HELLP complicated 49% of pregnancies; Fetal growth restriction complicated
61% of pregnancies. Early delivery (<34th week) occurred in 71% of pregnancies. Any
thrombophilia factor was present in 29% of the women. Severe preeclampsia was associated
with protein S deficiency (p = 0.01). Fetal growth restriction was associated with anti-phospholipid antibodies (p < 0.01). Early onset preeclampsia was associated with anti-phospholipid antibodies (p = 0.01). Extensive placental infarction (>10%) was associated with anti-phospholipid
antibodies (p < 0.01). Low placental weight (<5th percentile) was associated with hyperhomocysteineamia
(p = 0.03). No other associations were observed.
Conclusions
Early onset preeclampsia, especially if complicated by fetal growth restriction, are
associated with anti-phospholipid antibodies. Other phenotypes of preeclampsia, especially
HELLP syndrome, were not associated with thrombophilia. We advise only to test for
anti-phospholipid antibodies after early onset preeclampsia, especially if complicated
by fetal growth restriction. We suggest enough evidence is presented to justify no
further studies are needed.
Keywords
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References
- Pre-eclampsia.Lancet. 2010; 376: 631-644
- Thrombophilia and pregnancy.Reprod Biol Endocrinol. 2003; 1: 111
- Coagulation in pregnancy.Best Pract Res Clin Obstet Gynaecol. 2010; 24: 339-352
- Thrombophilia and pre-eclampsia.Semin Thromb Hemost. 2011; 37: 106-110
- Placental pathology in early onset pre-eclampsia and intra-uterine growth restriction in women with and without thrombophilia.Placenta. 2002; 23: 337-342
- The two stage model of preeclampsia: variations on the theme.Placenta. 2009; 30: S32-S37
- Do placental weights have clinical significance?.Hum Pathol. 1987; 18: 387-391
- Thrombophilias and adverse pregnancy outcome – a confounded problem!.Thromb Haemost. 2008; 99: 77-85
- Underlying disorders associated with severe early-onset preeclampsia.Am J Obstet Gynecol. 1995; 173: 1042-1048
- Thrombophilia is significantly associated with severe preeclampsia: results of a large-scale, case-controlled study.Hypertension. 2005; 46: 1270-1274
- Prospective studies of the association between anticardiolipin antibody and outcome of pregnancy.Obstet Gynecol. 1995; 86: 555-559
- Postnatal screening for thrombophilia in women with severe pregnancy complications.Obstet Gynecol. 2001; 97: 753-759
- Hyperhomocysteinaemia and protein S deficiency in complicated pregnancies.Br J Obstet Gynaecol. 1997; 104: 1248-1254
- Relationship between thrombophilic disorders and type of severe early-onset hypertensive disorder of pregnancy.Hypertens Pregnancy. 2007; 26: 433-445
- High prevalence of hemostatic abnormalities in women with a history of severe preeclampsia.Am J Obstet Gynecol. 1999; 180: 1146-1150
- Hyperhomocysteinemia and other thrombotic risk factors in women with placental vasculopathy.BJOG. 2000; 107: 785-791
- Periconception folic acid supplementation, fetal growth and the risks of low birth weight and preterm birth: the Generation R Study.Br J Nutr. 2009; 102: 777-785
- Clinical differences between early-onset HELLP syndrome and early-onset preeclampsia during pregnancy and at least 6 months postpartum.Am J Obstet Gynecol. 2010; 202: 271.e1-271.e5
- Inherited thrombophilia and preeclampsia within a multicenter cohort: the Montreal Preeclampsia Study.Am J Obstet Gynecol. 2009; 200 (discussion e1–5): 151.e1-151.e9
- Severe preeclampsia and high frequency of genetic thrombophilic mutations.Obstet Gynecol. 2000; 96: 45-49
- Factor V Leiden and prothrombin G20210A mutations in pregnancies with adverse outcome.J Matern Fetal Neonatal Med. 2002; 12: 267-273
- Factor V Leiden and factor II G20210A in preeclampsia and HELLP syndrome.Acta Obstet Gynecol Scand. 2002; 81: 1095-1100
- Is there an increased maternal-infant prevalence of Factor V Leiden in association with severe pre-eclampsia?.BJOG. 2002; 109: 191-196
- Frequency of factor V, prothrombin and methylenetetrahydrofolate reductase gene variants in preeclampsia.Gynecol Obstet Investig. 2002; 53: 84-87
- Increased frequency of genetic thrombophilia in women with complications of pregnancy.N Engl J Med. 1999; 340: 9-13
- Usefulness of screening for congenital or acquired hemostatic abnormalities in women with previous complicated pregnancies.Haemostasis. 1999; 29: 197-203
- Maternal factor V Leiden mutation is associated with HELLP syndrome in Caucasian women.Acta Obstet Gynecol Scand. 2008; 87: 635-642
- Detection of factor V Leiden mutation in severe pre-eclamptic Hungarian women.Clin Genet. 1998; 53: 478-481
- Factor V Leiden and thermolabile methylenetetrahydrofolate reductase gene variants in an East Anglian preeclampsia cohort.Hypertension. 1999; 33: 1338-1341
- The association of factor V leiden and prothrombin gene mutation and placenta-mediated pregnancy complications: a systematic review and meta-analysis of prospective cohort studies.PLoS Med. 2010; 7: e1000292
- High prevalence of the prothrombin gene mutation in women with intrauterine growth retardation, abruptio placentae and second trimester loss.Acta Obstet Gynecol Scand. 2000; 79: 963-967
- Antiphospholipid antibodies and preeclampsia: a case-control study.Obstet Gynecol. 2001; 97: 29-34
- Activated protein C resistance – in the absence of factor V Leiden – and pregnancy.J Thromb Haemost. 2006; 4: 361-366
- Hypertension in pregnancy: executive summary of the ACOG guideline.Obstet Gynecol. 2013; 122: 1122-1131
- The classification, diagnosis and management of the hypertensive disorders of pregnancy: a revised statement from the ISSHP.Pregnancy Hypertens. 2014; 4: 97-104
- Obstetric antiphospholipid syndrome: an update on pathophysiology and management.Semin Reprod Med. 2011; 29: 522-539
- Low-molecular-weight heparin added to aspirin in the prevention of recurrent early-onset pre-eclampsia in women with inheritable thrombophilia: the FRUIT-RCT.J Thromb Haemost. 2012; 10: 64-72
- Pathologic features of the placenta in women with severe pregnancy complications and thrombophilia.Obstet Gynecol. 2001; 98: 1041-1044
- Outcomes of subsequent pregnancy after first pregnancy with early-onset preeclampsia.Am J Obstet Gynecol. 2006; 195: 723-728
- Maternal thrombophilia and the risk of recurrence of preeclampsia.Am J Obstet Gynecol. 2009; 200: 46.e1-46.e5
- Thrombophilia in pregnancy: a systematic review.Br J Haematol. 2006; 132: 171-196
- Prospective evaluation of the risk conferred by factor V Leiden and thermolabile methylenetetrahydrofolate reductase polymorphisms in pregnancy.Arterioscler Thromb Vasc Biol. 2000; 20: 266-270
- The common prothrombotic factors in nulliparous women do not compromise blood flow in the feto-maternal circulation and are not associated with preeclampsia or intrauterine growth restriction.Am J Obstet Gynecol. 2004; 191: 2002-2009
- The factor V Leiden mutation may predispose women to severe preeclampsia.Am J Obstet Gynecol. 1996; 175: 902-905
- Inheritance and perinatal consequences of inherited thrombophilia in Greece.Int J Gynaecol Obstet. 2008; 100: 124-129
- Factor V Leiden is associated with pre-eclampsia but not with fetal growth restriction: a genetic association study and meta-analysis.J Thromb Haemost. 2008; 6: 1869-1875
- The GOAL study: a prospective examination of the impact of factor V Leiden and ABO(H) blood groups on haemorrhagic and thrombotic pregnancy outcomes.Br J Haematol. 2008; 140: 236-240
- Prothrombin gene G20210A mutation and obstetric complications.Obstet Gynecol. 2010; 115: 14-20
Article info
Publication history
Published online: September 25, 2015
Accepted:
September 17,
2015
Received in revised form:
September 4,
2015
Received:
July 29,
2015
Identification
Copyright
© 2015 Elsevier Ireland Ltd. Published by Elsevier Inc. All rights reserved.
