Maternal Factor V Leiden Mutation Is Associated With HELLP Syndrome in Caucasian Women

AbstractPregnancy results in alterations in coagulation processes, which may increase the risk of thrombosis. Inherited thrombophilia mutations may further increase this risk, possibly through alterations in the placenta, which may result in pregnancy complications such as poor fetal growth. The purpose of our study is to evaluate the association of fetal growth, approximated by birth weight for gestational age percentile, with genetic markers of thrombophilia and placental characteristics related to vascular malperfusion. We analyzed data from the Stillbirth Collaborative Research Network's population-based case–control study conducted in 2006–2008. Study recruitment occurred in five states: Rhode Island and counties in Massachusetts, Georgia, Texas, and Utah. The analysis was restricted to singleton, nonanomalous live births ≤42 weeks' gestation with a complete placental examination and successful testing for ≥1 thrombophilia marker (858 mothers, 902 infants). Data were weighted to account for oversampling, differential consent, and availability of placental examination. We evaluated five thrombophilia markers: factor V Leiden, factor II prothrombin, methylenetetrahydrofolate reductase A1298C and C677T, and plasminogen activator inhibitor type 1 in both maternal blood and placenta/cord blood. We modeled maternal and fetal thrombophilia markers separately using linear regression. Maternal factor V Leiden mutation was associated with a 13.16-point decrease in adjusted birth weight percentile (95% confidence interval: −25.50, −0.82). Adjustment for placental abnormalities related to vascular malperfusion did not affect the observed association. No other maternal or fetal thrombophilia markers were significantly associated with birth weight percentile. Maternal factor V Leiden may be associated with fetal growth independent of placental characteristics.

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HELLP Syndrome and Cerebral Venous Sinus Thrombosis Associated with Factor V Leiden Mutation during Pregnancy

Case Reports in Obstetrics and Gynecology ◽

10.1155/2014/582890 ◽

2014 ◽

Vol 2014 ◽

pp. 1-3 ◽

Cited By ~ 1

Author(s):

Zeynep Ozcan Dag ◽

Yuksel Işik ◽

Yavuz Simsek ◽

Ozlem Banu Tulmac ◽

Demet Demiray

Keyword(s):

Hellp Syndrome ◽

Sinus Thrombosis ◽

Factor V Leiden ◽

Cerebral Venous Sinus Thrombosis ◽

Venous Sinus ◽

Factor V ◽

Hormonal Changes ◽

Factor V Leiden Mutation ◽

Venous Sinus Thrombosis ◽

Increased Risk

Preeclampsia is a leading cause of maternal mortality and morbidity worldwide. The neurological complications of preeclampsia and eclampsia are responsible for a major proportion of the morbidity and mortality for women and their infants alike. Hormonal changes during pregnancy and the puerperium carry an increased risk of venous thromboembolism including cerebral venous sinus thrombosis (CVST). Factor 5 leiden (FVL) is a procoagulant mutation associated primarily with venous thrombosis and pregnancy complications. We report a patient with FVL mutation who presented with CVST at 24th week of pregnancy and was diagnosed as HELLP syndrome at 34th week of pregnancy.

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Genetic Aspects of Preeclampsia and the HELLP Syndrome

Journal of Pregnancy ◽

10.1155/2014/910751 ◽

2014 ◽

Vol 2014 ◽

pp. 1-13 ◽

Cited By ~ 30

Author(s):

Kjell Haram ◽

Jan Helge Mortensen ◽

Bálint Nagy

Keyword(s):

Hellp Syndrome ◽

Genetic Diseases ◽

Factor V Leiden ◽

Mthfr C677t ◽

Envelope Gene ◽

Factor V ◽

Vegf Mrna ◽

Factor V Leiden Mutation ◽

Blood Flows ◽

Increased Risk

Both preeclampsia and the HELLP syndrome have their origin in the placenta. The aim of this study is to review genetic factors involved in development of preeclampsia and the HELLP syndrome using literature search in PubMed. A familial cohort links chromosomes 2q, 5q, and 13q to preeclampsia. The chromosome 12q is coupled with the HELLP syndrome. TheSTOX1gene, theERAP1and 2 genes, the syncytin envelope gene, and the−670 Fasreceptor polymorphisms are involved in the development of preeclampsia. TheACVR2Agene on chromosome 2q22 is also implicated. The toll-like receptor-4 (TLR-4) and factor V Leiden mutation participate both in development of preeclampsia and the HELLP syndrome. Carriers of the TT and the CC genotype of theMTHFR C677Tpolymorphism seem to have an increased risk of the HELLP syndrome. The placental levels of VEGF mRNA are reduced both in women with preeclampsia and in women with the HELLP syndrome. The BclI polymorphism is engaged in development of the HELLP syndrome but not in development of severe preeclampsia. TheACE I/Dpolymorphism affects uteroplacental and umbilical artery blood flows in women with preeclampsia. In women with preeclampsia and the HELLP syndrome several genes in the placenta are deregulated. Preeclampsia and the HELLP syndrome are multiplex genetic diseases.

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Incidence of the Factor V Leiden-mutation, Coagulation Inhibitor Deficiency, and Elevated Antiphospholipid-antibodies in Patients with Preeclampsia or HELLP–Syndrome

Thrombosis Research ◽

10.1016/s0049-3848(00)00312-1 ◽

2000 ◽

Vol 100 (4) ◽

pp. 363-365 ◽

Cited By ~ 44

Author(s):

Georg–Friedrich von Tempelhoff ◽

Lothar Heilmann ◽

Eberhard Spanuth ◽

Erich Kunzmann ◽

Gerhard Hommel

Keyword(s):

Hellp Syndrome ◽

Antiphospholipid Antibodies ◽

Factor V Leiden ◽

Factor V ◽

Factor V Leiden Mutation ◽

Coagulation Inhibitor

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ProC® Global Assay in the Evaluation of Women with History of Severe Preeclampsia or HELLP Syndrome

Clinical and Applied Thrombosis/Hemostasis ◽

10.1177/107602960200800403 ◽

2002 ◽

Vol 8 (4) ◽

pp. 319-324 ◽

Cited By ~ 6

Author(s):

Lothar Heilmann ◽

Georg-Friedrich v. Tempelhoff ◽

Kuhnhart Pollow

Keyword(s):

Hellp Syndrome ◽

Protein C ◽

Activated Protein C ◽

Factor V Leiden ◽

Protein S ◽

Anticardiolipin Antibodies ◽

Factor V ◽

Factor V Leiden Mutation ◽

Lupus Anticoagulants ◽

Apc Resistance

Preeclampsia/HELLP syndrome has been associated with a high incidence of defects in the protein C pathway and increased anticardiolipin-antibodies/lupus anticoagulants. It is also apparent that thrombophilia is responsible for other pregnancy complications, such as recurrent spontaneous abortion, fetal growth restriction, intrauterine fetal death, and abruptio placentae. ProC® Global is a new global clotting assay designed to evaluate the abnormalities in the protein C anticoagulant pathway. It is based on the ability of endogenous activated protein C, generated by activation of protein C by Protac®, to prolong an activated partial thromboplastin time. A total of 61 patients with a history of severe preeclampsia or HELLP syndrome and 61 normal pregnant women (controls) were evaluated, 15 of whom had factor V Leiden mutation, 12 had protein C/S deficiency, 30 had a repeated lupus anticoagulants, and 27 increased anticardiolipin antibodies (ACA). All carriers of factor V Leiden mutation (N= 15) as well as all the patients with low activated protein C (APC) resistance ratio (N= 15) had a ProC® Global normalized ratio (NR) less than 0.80 (sensitivity 100%). Twenty-four patients positive for the lupus anticoagulants (LA) and 19 patients positive for ACA (> 5.0 IgG U/mL) had a ProC® Global NR less than 0.8, while six and eight, respectively, had a ProC® Global NR greater than 0.8 (sensitivity, 70%-80%). The detection of a reduced protein C/protein S activity (<70%) was low (sensitivity, 33%-44%). In 25 cases with pathologic ProC® Global results, a thrombophilic defect (protein S/LA/ACA without APC resistance) was diagnosed in 18 women; but in 7 cases, no known thrombophilic defect was present. ProC® Global is a new screening test to identify patients with defects of the protein C system and an activated clotting system in preeclampsia but cannot correctly cover each thrombophilic component.

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Pre- and intraretinal haemorrhages in a 22-week-old fetus of a mother suffering from HELLP syndrome and factor V Leiden mutation with deep vein thrombosis

Acta Ophthalmologica ◽

10.1111/aos.13090 ◽

2016 ◽

Vol 95 (1) ◽

pp. e83-e84 ◽

Cited By ~ 3

Author(s):

Martina Christina Herwig ◽

Annette M. Müller ◽

Klaus Kuchelmeister ◽

Karin U. Loeffler

Keyword(s):

Deep Vein Thrombosis ◽

Hellp Syndrome ◽

Factor V Leiden ◽

Factor V ◽

Factor V Leiden Mutation ◽

Vein Thrombosis ◽

Deep Vein

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Maternal Factor V Leiden Mutation in Pre-eclampsia: A Case-Control South Eastern Indian Tertiary Care Hospital Based Study

JOURNAL FOR CLINICAL AND DIAGNOSTIC RESEARCH ◽

10.7860/jcdr/2020/42744.13497 ◽

2020 ◽

Author(s):

Krishnaveni Changalvala ◽

Pushpa Kotur ◽

Mitesh Shetty ◽

KS Praveen Kumar ◽

TV Jagadish ◽

...

Keyword(s):

Tertiary Care Hospital ◽

Tertiary Care ◽

Factor V Leiden ◽

Case Control ◽

Factor V ◽

Care Hospital ◽

Factor V Leiden Mutation ◽

Maternal Factor ◽

South Eastern

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Thrombophilia and risk of VTE recurrence according to the age at the time of first VTE manifestation

VASA ◽

10.1024/0301-1526/a000447 ◽

2015 ◽

Vol 44 (4) ◽

pp. 313-323 ◽

Cited By ~ 6

Author(s):

Lea Weingarz ◽

Marc Schindewolf ◽

Jan Schwonberg ◽

Carola Hecking ◽

Zsuzsanna Wolf ◽

...

Keyword(s):

Factor V Leiden ◽

Cox Proportional Hazards ◽

First Episode ◽

Factor V ◽

Factor V Leiden Mutation ◽

Younger Patients ◽

Risk Of Recurrence ◽

G20210a Mutation ◽

Increased Risk ◽

The Impact

Abstract. Background: Whether screening for thrombophilia is useful for patients after a first episode of venous thromboembolism (VTE) is a controversial issue. However, the impact of thrombophilia on the risk of recurrence may vary depending on the patient’s age at the time of the first VTE. Patients and methods: Of 1221 VTE patients (42 % males) registered in the MAISTHRO (MAin-ISar-THROmbosis) registry, 261 experienced VTE recurrence during a 5-year follow-up after the discontinuation of anticoagulant therapy. Results: Thrombophilia was more common among patients with VTE recurrence than those without (58.6 % vs. 50.3 %; p = 0.017). Stratifying patients by the age at the time of their initial VTE, Cox proportional hazards analyses adjusted for age, sex and the presence or absence of established risk factors revealed a heterozygous prothrombin (PT) G20210A mutation (hazard ratio (HR) 2.65; 95 %-confidence interval (CI) 1.71 - 4.12; p < 0.001), homozygosity/double heterozygosity for the factor V Leiden and/or PT mutation (HR 2.35; 95 %-CI 1.09 - 5.07, p = 0.030), and an antithrombin deficiency (HR 2.12; 95 %-CI 1.12 - 4.10; p = 0.021) to predict recurrent VTE in patients aged 40 years or older, whereas lupus anticoagulants (HR 3.05; 95%-CI 1.40 - 6.66; p = 0.005) increased the risk of recurrence in younger patients. Subgroup analyses revealed an increased risk of recurrence for a heterozygous factor V Leiden mutation only in young females without hormonal treatment whereas the predictive value of a heterozygous PT mutation was restricted to males over the age of 40 years. Conclusions: Our data do not support a preference of younger patients for thrombophilia testing after a first venous thromboembolic event.

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