Tamoxifen induces resistance to activated protein C

Rühl, Heiko; Schröder, Lars; Müller, Jens; Fimmers, Rolf; Sukhitashvili, Shorena; Welz, Julia; Kuhn, Walther; Oldenburg, Johannes; Rudlowski, Christian; Pötzsch, Bernd

doi:10.1016/j.thromres.2014.02.004

Cited by 20 publications

(13 citation statements)

References 38 publications

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“…Concerning our results, which showed a significant presence of the FV Leiden mutation among tamoxifen users with VTE, the APC resistance test, easy to perform and highly sensitive to the presence of the FV Leiden mutation [19] should be performed before tamoxifen therapy as a logical procedure in the prevention of thrombosis in women with breast cancer. The importance of risk evaluation for thrombosis is even greater if we take into account recent findings pointing to the development of acquired APC resistance under tamoxifen [7].…”

Section: Discussionmentioning

confidence: 99%

“…Thrombotic complications among women during tamoxifen therapy seem likely to arise from its pronounced thrombogenic effect. This leads to changes in the hemostatic system, previously described as an association of intrinsic estrogenic activity and to possible changes in terms of the reduction of the antithrombin and protein C levels [4][5][6] or the presence of acquired APC resistance [7]. Breast cancer is the most common cancer worldwide for females, and the second most common cancer overall, with more than 1,676,000 new cases diagnosed in 2012 (25% of female cases and 12% of the total) [8].…”

Section: Introductionmentioning

confidence: 99%

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Factor V Leiden mutation and high FVIII are associated with an increased risk of VTE in women with breast cancer during adjuvant tamoxifen — Results from a prospective, single center, case control study

Kovač

Kovac

Tomašević

et al. 2015

European Journal of Internal Medicine

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Factor V Leiden mutation and high FVIII are associated with an increased risk of VTE in women with breast cancer during adjuvant tamoxifen — Results from a prospective, single center, case control study

Kovač

Kovac

Tomašević

et al. 2015

European Journal of Internal Medicine

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“…This could be due to increased levels of estrogen (e.g. during pregnancy [15], use of oral contraceptive (OC) [16] or tamoxifen treatment [17]), which decreases the aPC ratio (i.e. inducing aPC resistance) [1].…”

Section: Discussionmentioning

confidence: 99%

The association between activated protein C ratio and Factor V Leiden are gender-dependent

Hansen

Nybo

2019

Clinical Chemistry and Laboratory Medicine (CCLM)

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Background The most common cause of activated protein C (aPC) resistance is a missense substitution (Arg506Gln), known as Factor V Leiden (FVL). Due to its low cost, many laboratories use the aPC ratio as a primary test with a unisex cut-off. However, the association between the aPC ratio and FVL including any relation to gender has been sparsely investigated. Methods Results of the aPC ratio and FVL analyses from 1081 patients referred to the Thrombophilia Clinic at Odense University Hospital were compared. Results In 153 FVL positive patients, the mean aPC ratio was 2.1 ± 0.3, which differed from 2.7 ± 0.4 in FVL negative individuals (p < 0.01). The receiver operating characteristics (ROC), with area under the curve (AUC) of 0.93, indicated the optimal aPC cut-off at 2.3–2.4, with sensitivity 89%–94%, specificity 71%–84%, positive predictive value 35%–48% and negative predictive value 98%–99%. In FVL positive females, the mean aPC ratio was 2.0 ± 0.3, which differed from males (2.1 ± 0.3, p < 0.05). In FVL negative females, the mean aPC ratio was 2.6 ± 0.4, also different from males (2.8 ± 0.5, p < 0.01). Of note, 35% of FVL negative females had an aPC ratio ≤2.4 against 18% in males (p < 0.01). Conclusions Our results indicate that the aPC ratio is lower in females than in males. Due to a high negative predictive value the aPC ratio can be used as a first line test for FVL, but those found positive must be confirmed with a DNA test.

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“…Thrombin generation tests used in this variant are capable of detecting hereditary APC resistance (e.g., FVL mutation) as well as acquired forms of impaired APC sensitivity (e.g., the one caused by ligands of estrogen receptors such as the estrogen components of CHCs and other drugs). [75][76][77]…”

Section: Assessment Of Prothrombotic Abnormalities and Complex Coagulmentioning

confidence: 99%

Can We Measure the Individual Prothrombotic or Prohemorrhagic Tendency by Global Coagulation Tests?

et al. 2020

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Hemostasis is a complex process in which abnormalities can cause shifts toward prothrombotic or prohemorrhagic states resulting in thrombosis or bleeding, respectively. Several coagulation tests may be required to characterize these defects but may yet not always reflect a patient's true hemostatic capacity. Thus, global coagulation tests aiming to simulate the coagulation process in vitro instead of measuring single components thereof are certainly of interest to assess prothrombotic or prohemorrhagic tendencies. This review describes the development and application of global coagulation tests, concentrating on the more widely used methods of viscoelastometry and thrombin generation. A focus is placed on conditions characterized by simultaneous changes of various components of hemostasis, such as anticoagulant therapy or hormone-induced coagulopathy, in which global coagulation tests are especially promising. If the key challenges of standardization and automation of these tests are solved, as is the case with automated thrombogram or clot waveform analysis, global coagulation assays will play an important role in the future of laboratory diagnostics of hemostasis and thrombosis.

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Tamoxifen induces resistance to activated protein C

Cited by 20 publications

References 38 publications

Factor V Leiden mutation and high FVIII are associated with an increased risk of VTE in women with breast cancer during adjuvant tamoxifen — Results from a prospective, single center, case control study

Factor V Leiden mutation and high FVIII are associated with an increased risk of VTE in women with breast cancer during adjuvant tamoxifen — Results from a prospective, single center, case control study

The association between activated protein C ratio and Factor V Leiden are gender-dependent

Can We Measure the Individual Prothrombotic or Prohemorrhagic Tendency by Global Coagulation Tests?

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