Development of resistance to activated protein C during pregnancy

Cumming, A. M.; Tait, Robert C.; Fildes, S.; Yoong, A.; Keeney, S.; Hay, C. R. M.

doi:10.1097/00001721-199504000-00035

Cited by 53 publications

(76 citation statements)

References 4 publications

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“…It has also been shown recently that in women taking oral contraceptives or who are pregnant, this test may be unreliable as a means of detecting the Factor V Leiden abnormality. 9 10 Furthermore, this test often yields borderline results which may be difficult to interpret.…”

Section: Discussionmentioning

confidence: 99%

Development of a rapid DNA screening procedure for the Factor V Leiden mutation

Scobie

Dolan

et al. 1996

Molecular Pathology

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Aim-To develop a rapid, simple and highly specific DNA screening procedure based on the amplification refractory mutation system (ARMS) to detect the Leiden mutation in whole blood. Methods-ARMS PCR amplification primers with additional mismatches at either -2 or -3, which greatly improves specificity, were constructed to detect the normal Factor V gene and the Leiden mutation in whole blood samples from patients with abnormal clotting results. Results-Construction of ARMS primers with either an additional mismatch at -2 or -3 at the 3' end of the primer could be used to detect the Leiden mutation in 0.5 pl whole blood in under three hours. Primers destabilised at position -3 could be used at a lower annealing temperature, which gave greater sensitivity and are now routinely used. A control set of primers was included in the same reaction to act as a positive control. Conclusions-This rapid and specific assay for the factor V Leiden mutation is a useful addition to the investigation of patients with or at risk from thrombovascular disease.

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Section: Discussionmentioning

confidence: 99%

Development of a rapid DNA screening procedure for the Factor V Leiden mutation

Scobie

Dolan

et al. 1996

Molecular Pathology

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“…From the first application of the APC resistance assays in a routine setting, it became evident that in several common conditions a false-positive assay outcome can be obtained. Well-known examples are conditions such as pregnancy, 95 malignancy, 96 use of oral contraceptives (OCs), 97 and hormone replacement therapy. 98 In addition, the presence of lupus anticoagulants, 99 anti-APC antibodies, 100 or high FVIII levels 101 influences APC resistance tests.…”

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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“…Caesarian delivery is an independent risk factor for CVT. [25] Following any surgery protein C levels can decrease [26] also there is a pregnancy associated resistance to activated protein C. [27,28] It is a common traditional practice in this geographical region, where women are given restricted water in the post partum period. Regarding this practice there are many believes: (i) water restriction will result in more concentrated breast milk for the baby, (ii) less water intake will prevent loss of abdominal muscle tone and resultant pendulous abdomen, and (iii) restricted water intake during labour can prevent excessive bleeding during delivery.…”

Section: Discussionmentioning

confidence: 99%