Inherited Resistance To Activated Protein C Caused By Presence Of The FV:Q&lt;sup&gt;506&lt;/sup&gt; Allele As A Basis Of Venous Thrombosis

Dahlbäck, Björn; Zöller, Bengt; Hillarp, Andreas

doi:10.1159/000217311

Cited by 20 publications

(20 citation statements)

References 59 publications

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“…APC resistance caused by the FV Leiden mutation is a strong risk factor for venous thrombosis. Our study shows that a reduced sensitivity for APC in the absence of the FV Leiden mutation is also associated with an increased risk of venous thrombosis Because APCR is associated not only with recurrent pregnancy loss but also with maternal thrombotic events [50], we recommend screening of women who plan pregnancy for the existence of APC resistance, as suggested also elsewhere [51].…”

Section: Discussionsupporting

confidence: 56%

Association between adverse pregnancy outcomes and maternal factor V G1691A (Leiden) and prothrombin G20210A genotypes in women with a history of recurrent idiopathic miscarriages

et al. 2005

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Thrombophilia was implicated in the development of pregnancy complications, including recurrent idiopathic pregnancy loss, and is aggravated in women who are carriers of factor V G1691A (FV Leiden) and prothrombin (PRT) G20210A single-nucleotide polymorphisms (SNPs). Previous studies examined the role of FV-Leiden and PRT G20210A in recurrent pregnancy loss with conflicting results. Here we examined the prevalence of FV Leiden and PRT G20210A SNPs, in 200 women with 3 or more consecutive early (n = 87), late (n = 41), or early-late (n = 72) recurrent pregnancy losses, and 200 age-matched fertile parous control women. APC resistance (APCR) was detected functionally (measuring the activated clotting time triggered by activated factor X in presence of a fixed amount of purified APC), and FV-Leiden and PRT G20210A genotypes were assessed by PCR. The frequency of the mutant FV (0.1400 vs. 0.0276; P < 0.001) but not PRT 20210 (0.0100 vs. 0.0225; P = 0.159) allele was higher in patients than controls, respectively. APC resistance with factor V Leiden was seen in 27% of patients compared to 11.5% of controls, while APC resistance without factor V Leiden was seen in 12.5% of patients compared to 9.5% of controls. Regression analysis demonstrated that the significant predictors for early abortion was FV Leiden; those for late abortion were oral contraceptive, APCR, and FV Leiden; and predictors for early-late abortions were oral contraceptives, obesity, FV Leiden, and smoking. APC resistance and FV Leiden, as well as combination of both, are common thrombotic defects seen in women with idiopathic recurrent pregnancy loss, thus testing for these is recommended in women who have experienced recurrent miscarriages. Am.

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Section: Discussionsupporting

confidence: 56%

Association between adverse pregnancy outcomes and maternal factor V G1691A (Leiden) and prothrombin G20210A genotypes in women with a history of recurrent idiopathic miscarriages

et al. 2005

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“…This varies from 1% to 15% in different countries with a frequency of 3% reported in Italy and Spain and a frequency of 15% reported in Northern Sweden [33]. APCR in the general population and during pregnancy is reported to be most frequently caused by FVL mutation [34–36], inherited APCR.…”

Section: Discussionmentioning

confidence: 99%

Acquired Activated Protein C Resistance, Thrombophilia and Adverse Pregnancy Outcomes: A Study Performed in an Irish Cohort of Pregnant Women

Sedano-Balbás

Lyons

Cleary

et al. 2011

Journal of Pregnancy

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The combination of thrombophilia and pregnancy increases the risk of thrombosis and the potential for adverse outcomes during pregnancy. The most significant common inherited risk factor for thrombophilia is activated protein C resistance (APCR), a poor anticoagulant response of APC in haemostasis, which is mainly caused by an inherited single-nucleotide polymorphism (SNP), factor V G1691A (FV Leiden) (FVL), referred as inherited APCR. Changes in the levels of coagulation factors: FV, FVIII, and FIX, and anticoagulant factors: protein S (PS) and protein C (PC) can alter APC function causing acquired APCR. Prothrombin G20210A and methylenetetrahydrofolate reductase (MTHFR) C677T are prothrombotic SNPs which in association with APCR can also increase the risk of thrombosis amongst Caucasians. In this study, a correlation between an acquired APCR phenotype and increased levels of factors V, VIII, and IX was demonstrated. Thrombophilic mutations amongst our acquired APCR pregnant women cohort are relatively common but do not appear to exert a severe undue adverse effect on pregnancy.

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“…Yet, it is clear that changes of several important blood coagulation parameters (such as prothrombin, protein S, FVIII, and tissue factor pathway inhibitor) are involved. [102][103][104][105] …”

Section: Resistance To Apc In the Absence Of Fv Leidenmentioning

confidence: 99%

Congenital and Acquired Activated Protein C Resistance

Nicolaes¹,

Dahlbäck²

2003

Seminars in Vascular Medicine

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Resistance to the anticoagulant action of activated protein C, APC resistance, is a highly prevalent risk factor for venous thrombosis among individuals of Caucasian origin. In most cases, APC resistance is associated with a single missense mutation in the gene for coagulation factor V (FV (Leiden)), which predicts the replacement of Arg (506) with a Gln at one of the cleavage sites for APC in factor V. Factor V is a Janus-faced protein with dual functions, serving as an essential nonenzymatic cofactor in both pro- and anticoagulant pathways. Procoagulant factor Va, generated after proteolysis by thrombin or factor Xa, is a cofactor to factor Xa in the activation of prothrombin, whereas anticoagulant factor V, generated after proteolysis by APC, functions as a cofactor in the APC-mediated degradation of FVIIIa. The FV (Leiden) mutation affects the anticoagulant response to APC at two distinct levels of the coagulation pathway, as it impairs degradation of both activated factor V and activated factor VIII, the latter effect inasmuch as FVLeiden is a poor APC cofactor. Several other genetic traits, some of them quite common, are known to affect the anticoagulant response to APC, but none of them cause the same severe APC-resistance phenotype as FV (Leiden) and their importance as risk factors for thrombosis is unclear. A poor APC response may also result from acquired conditions, some of which are clearly involved in the pathogenesis of venous thrombosis. Venous thrombosis is a typical multifactorial disease, the pathogenesis of which involves multiple gene-gene and gene-environment interactions. In many patients with severe thrombophilia, APC resistance is found as a contributing risk factor.

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Inherited Resistance To Activated Protein C Caused By Presence Of The FV:Q<sup>506</sup> Allele As A Basis Of Venous Thrombosis

Cited by 20 publications

References 59 publications

Association between adverse pregnancy outcomes and maternal factor V G1691A (Leiden) and prothrombin G20210A genotypes in women with a history of recurrent idiopathic miscarriages

Association between adverse pregnancy outcomes and maternal factor V G1691A (Leiden) and prothrombin G20210A genotypes in women with a history of recurrent idiopathic miscarriages

Acquired Activated Protein C Resistance, Thrombophilia and Adverse Pregnancy Outcomes: A Study Performed in an Irish Cohort of Pregnant Women

Congenital and Acquired Activated Protein C Resistance

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