Severe Preeclampsia Associated with Coinheritance of Factor V Leiden Mutation and Protein S Deficiency

doi:10.1016/S0029-7844(97)00713-8

Obstetrics & Gynecology

Volume 91, Issue 5, Part 2, May 1998, Pages 812-814

https://doi.org/10.1016/S0029-7844(97)00713-8 Get rights and content

Abstract

Background: Inherited thrombophilic disorders are associated with an increased risk of venous thromboembolism during pregnancy. Preliminary research suggests that these disorders might also increase the risk for preeclampsia.

Case: A 29-year-old primigravida developed severe, early onset preeclampsia and postpartum deep venous thrombosis. Subsequent testing revealed coinheritance of the factor V Leiden mutation and protein S deficiency. Heparin prophylaxis was administered during two subsequent pregnancies without recurrence of either preeclampsia or venous thromboembolism.

Conclusion: Our patient’s inherited thrombophilia may have played a role in the development of preeclampsia, and anticoagulation during subsequent pregnancies may have prevented preeclampsia recurrence. An association between inherited thrombophilic disorders and preeclampsia is biologically plausible.

Section snippets

Case

A 29-year-old white primigravida presented at 31 weeks’ gestation with generalized edema, weight gain of 2 lb per week, elevated blood pressure and 4+ dipstick proteinuria. At regular prenatal visits her blood pressure was 100/60 mmHg, urine dipstick was normal, and a glucose screen at 28 weeks’ gestation was negative. At age 17, she had a spontaneous superficial thrombophlebitis of the left saphenous vein while taking oral contraceptives but was otherwise healthy. There was no history of

Comment

Our patient had severe early onset preeclampsia and postpartum deep vein thrombosis during her first pregnancy associated with coinheritance of the factor V Leiden mutation and protein S deficiency. Heparin prophylaxis was administered during two subsequent pregnancies, without recurrence of hypertension, preeclampsia, or venous thromboembolism.

Information on the prevalence of the factor V Leiden mutation or protein S deficiency in other family members is not available. However, the high

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Cited by (20)

Factor V Leiden mutation in pregnancy
2004, JOGNN - Journal of Obstetric, Gynecologic, and Neonatal Nursing
Citation Excerpt :
A systematic review by Alfirevic and colleagues (2002) revealed that women with placental abruption were more often heterozygous or homozygous for factor V Leiden mutation (odds ratio of 16.9) and that women with unexplained stillbirth were more likely to have the factor V Leiden mutation (odds ratio of 6.1). In multiple reports, activated protein C resistance has been associated with severe, early-onset preeclampsia (Dizon-Townson et al., 1996; Kahn, 1998). Women with hemolysis, elevated liver enzymes, and low platelet count (HELLP syndrome) have been noted to have a higher incidence of factor V Leiden mutation and activated protein C resistance due to unknown causes (Krauss et al., 1998).
Normal maternal adaptation to pregnancy significantly increases the risk for thrombus formation. Inherited thrombophilias further increase risk for deep venous thrombosis and adverse outcome in pregnancy. Factor V Leiden mutation is the most common inherited thrombophilia, occurring in approximately 5% of the White and 1% of the Black populations. Nurses should be knowledgeable about screening for and diagnosis of factor V Leiden mutation, risk reduction counseling, recommended care of the affected patient, and implications of anticoagulant therapy during the perinatal period.
Thalassemia intermedia and cavernous transformation of portal vein thrombosis in pregnancy
2003, European Journal of Obstetrics and Gynecology and Reproductive Biology
Thrombophilia, preeclampsia, and fetal demise: A case report
2002, Journal of Clinical Anesthesia
Maternal and fetal inherited thrombophilias are not related to the development of severe preeclampsia
2001, American Journal of Obstetrics and Gynecology
Objective: Thrombotic vascular disease may predispose patients to the development of preeclampsia. The purpose of this study was to determine whether maternal or fetal genotype frequencies of the inherited thrombophilic gene mutations (factor V Leiden, methylenetetrahydrofolate, and prothrombin) are altered in severe preeclampsia. Study Design: We performed a prospective cross-sectional study to compare the maternal and fetal genotype frequencies of factor V Leiden, methylenetetrahydrofolate, and prothrombin. One hundred ten patients with severe preeclampsia were matched for gestational age to 97 normotensive pregnancies. Umbilical cord blood was obtained from 92 control patients and 75 patients with preeclampsia. Deoxyribonucleic acid was extracted from leukocytes and polymerase chain reaction was performed. Polymerase chain reaction products were digested with the appropriate restriction enzyme and fractionated by gel electrophoresis. Genotype frequencies were calculated. Statistical significance was determined by the χ² test. Results: There were no significant differences between patients with severe preeclampsia and control patients regarding frequency of maternal factor V Leiden G/506/A mutation (4.4% vs 4.3%; P =.96), methylenetetrahydrofolate CC/667/TT mutation (9.6% vs 6.3%; P =.54), or prothrombin G/20210/A mutation (0% vs 1.1%; P =.92). In addition, no statistical difference could be found between fetal thrombophilias and the development of preeclampsia. Findings were similar in both white (n = 47) and African American (n = 63) preeclamptic subsets. Moreover, there was no association between any of the maternal or fetal genetic polymorphisms and the incidence of hemolysis, elevated liver enzymes, and low platelet count syndrome (n = 21); eclampsia (n = 12); or intrauterine growth restriction (n = 9). Conclusion: Inherited thrombophilias are not associated with severe preeclampsia. (Am J Obstet Gynecol 2001;185:153-7.)
Pathogenesis and genetics of pre-eclampsia
2001, Lancet
Citation Excerpt :
Genes that affect blood pressure have come under investigation and work on angiotensin has produced both positive and negative results.34–37 Associations with other genetic markers have been studied; examples are lipoprotein lipase;38 methylenetetrahydrofolate reductase;39 factor V Leiden;40 and apolipoprotein E.41 There have been many studies on the population association/candidate gene approach but there are no clear conclusions. In principle, a whole-genome linkage study is the most powerful way of identifying disease-susceptibility genes wherever there is a strong genetic component.
After more than a century of intensive research, pre-eclampsia and eclampsia remain an enigmatic set of conditions. Aberration of the interaction between placental and maternal tissue is probably the primary cause, but the exact nature of the differences from normal pregnancy remain elusive. In this review attempts to understand the sequence of physiological changes have concentrated on vascular endothelium and oxidative stress issues. There are genetic components to susceptibility, but the relative contributions of maternal and fetal genotypes are still unclear. Whole-genome mapping could ultimately define the causative genes.
Outcome of pregnancy in women with hereditary thrombophilia
2001, International Journal of Gynecology and Obstetrics
Objectives: The aims of this study are to review the outcome of pregnancy in women with thrombophilia, and investigate the possible beneficial effect of heparin therapy in these women. Methods: We reviewed the hospital records of 126 women who were referred to the high-risk obstetrical hematology clinic between June 1996 and December 1999. The placental histology and outcome of 39 pregnancies in 24 women with hereditary thrombophilia were studied, and pregnancies which were treated with heparin were compared with those without treatment. Results: An adverse pregnancy outcome occurred in 54% of the pregnancies. All seven miscarriages (18%) occurred in pregnancies that were not treated with heparin. However, heparin treatment did not prevent the development of obstetric complications in later pregnancies (odds ratio=0.955, 95% C.I.=0.255–3.577, Fisher's exact test). Excluding miscarriages, 28% of the placentas had thrombotic lesions, and the pregnancies with placental thrombotic lesions were more likely to have complications than those pregnancies without placental abnormalities (P=0.023, C.I.=1.257–5.197, Fisher's exact test). Conclusions: Pregnancy complications in cases of hereditary thrombophilia may be related to placental abnormalities. Heparin therapy is likely to be useful in preventing miscarriage in cases of hereditary thrombophilia.

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Case ReportsSevere Preeclampsia Associated with Coinheritance of Factor V Leiden Mutation and Protein S Deficiency

Abstract

Section snippets

Case

Comment

Am J Obstet Gynecol

Am J Obstet Gynecol

Am J Obstet Gynecol

Blood

Case Reports
Severe Preeclampsia Associated with Coinheritance of Factor V Leiden Mutation and Protein S Deficiency