Measurement of Activated Protein C Resistance during Menstrual Cycle in Women with and without the Leiden Mutation

M. L. Wramsby; K. Bremme; M. Blombäck

doi:10.1055/s-0037-1615642

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2001; 85(04): 614-618
DOI: 10.1055/s-0037-1615642

Review Articles

Schattauer GmbH

Measurement of Activated Protein C Resistance during Menstrual Cycle in Women with and without the Leiden Mutation

M. L. Wramsby

¹Department of Woman and Child Health, Karolinska Institutet

²Department of Surgical Sciences/Coagulation Research, Karolinska Institutet, Stockholm, Sweden

,

K. Bremme

¹Department of Woman and Child Health, Karolinska Institutet

,

M. Blombäck

²Department of Surgical Sciences/Coagulation Research, Karolinska Institutet, Stockholm, Sweden

› Author Affiliations

Abstract

Summary

Variations in the APC ratio during the menstrual cycle were assessed in 25 women without the Leiden mutation, and 10 women who were carrier of the mutation. Blood samples were collected at four occasions during one menstrual cycle. APC ratios were measured with two APTT based plasma methods with and without factor V depleted plasma.

None of the methods were able to accurately discriminate between mutated and non mutated women in all samples. Although a normalized method with factor V depleted plasma was favorable.

The levels of estradiol and progesterone did not differ between mutated and non mutated women.

Our findings suggest that the level of estradiol at estimated time of ovulation is of importance for the response to APC during luteal phase, since the women exhibiting the highest levels of estradiol at time for ovulation had the lowest response to APC.

Keywords

Menstrual cycle - APC ratio

Full Text

References

References
1 Bertina RM, Koeleman BP, Koster T, Rosendaal FR, Dirven RJ, de Ronde H, van der Velden PA, Reitsma PH. Mutation in blood coagulation factor V associated with resistance to activated protein C. Nature 1994; 369: 64-7.
2 Cumming AM, Tait RC, Fildes S, Yoong A, Keeney S, Hay CR. Development of resistance to activated protein C during pregnancy. Br J Haematol 1995; 90: 725-7.
3 Bokarewa MI, Wramsby M, Bremme K, Blombäck M. Variability of the response to activated protein C during normal pregnancy. Blood Coagul Fibrinolysis 1997; 8: 239-44.
4 Peek MJ, Nelson-Piercy C, Manning RA, de Swiet M, Letsky EA. Activated protein C resistance in normal pregnancy. Br J Obstet Gynaecol 1997; 104: 1084-6.
5 Wramsby ML, Bokarewa MI, Blombäck M, Bremme AK. Response to activated protein C during normal menstrual cycle and ovarian stimulation. Hum Reprod 2000; 15: 795-7.
6 Dahlbäck B, Carlsson M, Svensson PJ. Familial thrombophilia due to a previously unrecognized mechanism characterized by poor anticoagulant response to activated protein C: prediction of a cofactor to activated protein C. Proc Natl Acad Sci USA 1993; 90: 1004-8.
7 Bokarewa M, Falk G, Sten-Linder M, Egberg N, Blombäck M, Bremme K. Thrombotic risk factors and oral contraception. J Lab Clin Med 1995; 126: 294-8.
8 Gandrille S, Alhenc-Gelas M, Aiach M. A rapid screening method for the factor V Arg506-Gln mutation. Blood Coag Fibrinolysis 1995; 6: 245-8.
9 Sidelmann J, Gram J, Peersen OD, Jespersen J. Influence of plasma platelets on activated protein C resistance assay. Thromb Haemost 1995; 74: 993-4.
10 de Ronde H, Bertina RM. Laboratory diagnosis of APC resistance: A critical evaluation of the test and the development of diagnostic criteria. Thromb Haemost 1994; 72: 880-6.
11 Jorquera JI, Montoro JM, Aznar J. Modified test for activated protein C resistance. Lancet 1994; 344: 1162-3.
12 Trossaert M, Conard J, Horellou MH, Samama MM, Ireland H, Bayston TA, Lane DA. Modified APC resistance assay for patients on oral anticoagulants. Lancet 1994; 344: 1709-00.
13 Marieke CH, de Visser FR, Bertina RM. A reduced sensitivity for protein C in the absence of Factor V Leiden increases the risk of venous thrombosis. Blood 1999; 93: 1271-6.
14 Castaman G, Tosetto A, Ruggeri M, Rodeghiero F. Pseudohomozygosity for activated protein C resistance is a risk factor for venous thrombosis. Br J Haematol 1999; 106: 232-6.
15 Bernardi F, Faioni EM, Castoldi E, Lunghi B, Castaman G, Sacchi E, Mannucci PM. A factor V genetic component differing from factor V R506Q contributes to the activated protein C resistance phenotype. Blood 1997; 90: 1552-7.
16 Williamson D, Brown K, Luddington R, Baglin C, Baglin T. Factor V Cambridge: a new mutation (Arg306→Thr) associated with resistance to activated protein C. Blood 1998; 91: 1140-4.
17 Franco RF, Elion J, Tavella MH, Santos SE, Zago MA. The prevalence of factor V Arg306→Thr (factor V Cambridge) and factor V Arg306→Gly mutations in different human populations. Thromb Haemost 1999; 81: 312-3.
18 Winkler UH, Daume E, Sudik R, Oberhoff C, Bier U, Hallmann C, Andreas JO, Schindler AE. A comparative study of the hemostatic effects of two monophasic oral contraceptives containing 30 mg ethinylestradiol and either 2 mg chlormadinone acetate or 150 mg desogestrel. Eur J. Contracept Reprod Health Care 1999; 4: 145-54.
19 Rosing J, Middeldorp S, Curvers J, Thomassen C, Nicolaes G, Meijers J, Bouma B, Büller H, Prins M, Tans G. Low-dose oral contraceptives and acquired resistance to activated protein C: a randomised cross-over study. Lancet 1999; 354: 2036-40.
20 Andersson O, Blombäck M, Bremme K, Wramsby H. Prediction of changes in levels of haemostatic variables during menstrual cycle and ovarian hyperstimulation. Thromb Haemost 1997; 77: 901-4.