Activated protein C resistance caused by Arg506Gln mutation in factor Va

Greengard, JudithS.; Sun, Xiuli; Xu, Xiao; Fernández, J. A.; Griffin, JohnH.; Evatt, Bruce L.

doi:10.1016/s0140-6736(94)92497-x

Cited by 313 publications

(173 citation statements)

References 5 publications

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“…The defect, called APC resistance, is often caused by a mutation Greengard et al, 1994;Voorberg et al, 1994; in factor V (factor V Leiden ) at a predominant APC cleavage site (Arg 506 → Gln). APC resistance associated with factor V Leiden is a hereditary defect that increases the risk for venous thrombosis some 7-fold in the case of heterozygosity (Koster et al, 1993;Rosendaal et al, 1995) and 80-fold in the case of homozygosity (Rosendaal et al, 1995).…”

Section: Discussionmentioning

confidence: 99%

“…This defect, called APC resistance, appears to be a common hereditary risk factor for venous thrombosis (Griffin et al, 1993;Koster et al, 1993;Rosendaal et al, 1995;, which in the majority of the cases is associated with a single point mutation in factor V Greengard et al, 1994;Voorberg et al, 1994;. This mutation, often referred to as factor V Leiden , causes the replacement of an amino acid (Arg506 → Gln) at a predominant APC cleavage site which renders the activated form of factor V, factor Va, less susceptible to proteolysis by APC (Aparicio & Dahlbäck, 1996;Heeb et al, 1995;Kalafatis et al, 1995;Nicolaes et al, 1995).…”

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confidence: 99%

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Acquired APC resistance and oral contraceptives: differences between two functional tests

Curvers¹,

Thomassen²,

Nicolaes³

et al. 1999

Br J Haematol

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Summary.Resistance to activated protein C (APC) is often associated with a mutation in factor V (factor V Leiden ). Individuals without factor V Leiden who exhibit a response in functional APC-resistance tests similar to that of carriers of factor V Leiden are considered to be acquired APC resistant. This phenomenon is particularly observed in women using oral contraceptives (OC).In the present study we compared the response to APC in plasma from normal individuals, carriers of factor V Leiden and women who use OC using functional tests that either quantify the effect of APC on the endogenous thrombin potential (ETP) or on the activated partial thromboplastin time (aPTT).Both tests discriminated equally well between individuals with and without factor V Leiden who were not using OC. In contrast to the aPTT-based test, the ETP-based assay yielded significant differences in sensitivity to APC between non-OC users and OC users and between users of second and third generation OC. Since there was no correlation between APCsensitivity determined with both assays in non-carriers of factor V Leiden and in women who use OC and a poor correlation in carriers of factor V Leiden , we propose that other plasma components differentially modulate the response to APC in the aPTT-and ETP-based APC-resistance tests and that OC change the level of plasma protein(s) that modulate the effect of APC on thrombin formation initiated via the extrinsic coagulation pathway.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Acquired APC resistance and oral contraceptives: differences between two functional tests

Curvers¹,

Thomassen²,

Nicolaes³

et al. 1999

Br J Haematol

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“…In factor Va, these are R306, R506, and less importantly, R679. The molecular basis of FV Leiden is a missense mutation in the factor V (FV) gene at G1691A, resulting in R506 being changed to glutamine (R506Q) [8][9][10]. This change slows the inactivation of factor Va by APC, that is, factor V "resists" being degraded by APC, thereby creating a genetic risk factor that in association with environmental risk factors causes an increased risk for venous thrombosis.…”

Section: Background and Molecular Basis Of Fv Leiden And Activated Prmentioning

confidence: 99%

“…Some studies attribute more than 95% of cases of APC resistance to the FV Leiden mutation [3,9,12]. FV Leiden is present in heterozygous form in 5% of the general Caucasian population and is less common or rare in other ethnic groups [13][14][15][16][17][18].…”

Section: Background and Molecular Basis Of Fv Leiden And Activated Prmentioning

confidence: 99%

Factor VLeiden

2015

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Factor V Leiden (FV Leiden ) is a common hereditary thrombophilia that causes activated protein C (APC) resistance. This review describes many of the most fascinating features of FV Leiden , including background features, mechanisms of hypercoagulability, the founder mutation concept, the "FV Leiden paradox," synergistic interaction with other thrombotic risk factors, the intertwined relationship between FV Leiden and APC resistance testing, and other, uncommon mutations implicated in causing APC resistance. In addition, there are several conditions where laboratory tests for APC resistance and FV Leiden are or can be discrepant, including lupus anticoagulants, anticoagulants such as direct thrombin inhibitors (dabigatran, argatroban, and bivalirudin) and rivaroxaban, as well as pseudohomozygous, pseudo-wildtype, liver transplant, and bone marrow transplant patients. The laboratory test error rate for FV Leiden is also presented.

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“…It is caused by a single point mutation in the factor V gene (FV : R506Q or factor V Leiden) [4][5][6][7]. The FV : R506Q mutation results in replacement of arginine (R) by glutamine (Q) at position 506.…”

Section: Introductionmentioning

confidence: 99%

The factor VR506Q mutation causing APC resistance is highly prevalent amongst unselected outpatients with clinically suspected deep venous thrombosis

Svensson

Zöller

Mattiasson

et al. 1997

Journal of Internal Medicine

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Abstract. Svensson PJ, Zo$ ller B, Mattiasson I, Dahlba$ ck B (University of Lund, Malmo$ , Sweden). The factor VR506Q mutation causing APC resistance is highly prevalent among unselected outpatients with clinically suspected deep venous thrombosis. J Intern Med 1997 ; 241 : 379-85.Objective. Resistance to activated protein C (APC resistance), caused by a single point mutation in the factor V gene (FV : R506Q), is a major risk factor for venous thrombosis. As the significance of this mutation among unselected outpatients with deep-vein thrombosis (DVT) is not established, we have studied its prevalence among consecutive outpatients attending the emergency room due to a clinically suspected DVT. Design, setting and subjects. The FV : R506Q mutation was determined in 223 consecutive Swedish outpatients with clinically suspected DVT, and in 288 healthy controls. Using phlebography, the patients were classified as DVT-positive or DVTnegative. Main outcome measure. The prevalence of FV : R506Q mutation. Results. The prevalence of the FV : R506Q mutation

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Activated protein C resistance caused by Arg506Gln mutation in factor Va

Cited by 313 publications

References 5 publications

Acquired APC resistance and oral contraceptives: differences between two functional tests

Acquired APC resistance and oral contraceptives: differences between two functional tests

Factor VLeiden

The factor VR506Q mutation causing APC resistance is highly prevalent amongst unselected outpatients with clinically suspected deep venous thrombosis

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