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Oral contraceptives and venous thrombosis: different sensitivities to activated protein C in women using second- and third-generation oral contraceptives.
Br J Haematol. 1997 Apr; 97(1):233-8.BJ

Abstract

Epidemiological studies have shown that women who use third-generation oral contraceptives (OC) containing desogestrel, gestodene or norgestimate have a higher risk of venous thrombosis than women who use second-generation OC containing levonorgestrel. It is also known that a mutation in factor V (factor V(Leiden)), which results in resistance to activated protein C (APC) and which is the most common cause of hereditary thrombophilia, potentiates the prothrombotic effect of OC. Effects of APC on thrombin generation in the plasma of women using OC were compared to the response to APC in non-OC users and in individuals that were heterozygous or homozygous for factor V(Leiden). The response towards APC was evaluated on basis of the ratio (APC-sr) of the time integrals of thrombin formation determined in the presence and absence of APC. Compared with women not using OC, women who used OC exhibited a significantly decreased sensitivity to APC (P<0.001), independent of the kind of OC used. Women who used third-generation monophasic OC were significantly less sensitive to APC than women using second-generation OC (P<0.001) and had APC-sr that did not significantly differ from heterozygous female carriers of factor V(Leiden) who did not use OC. Women who were heterozygous for factor V(Leiden) and used OC had APC-sr in the range of homozygous carriers of factor V(Leiden). Two women who started OC therapy had significantly elevated APC-sr within 3 d. Acquired APC resistance may explain the epidemiological observation of increased risk for venous thrombosis in OC users, especially in women using third-generation OC.

Authors+Show Affiliations

Rosing J
Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University, The Netherlands.
Tans G
No affiliation info available
Nicolaes GA
No affiliation info available
Thomassen MC
No affiliation info available
van Oerle R
No affiliation info available
van der Ploeg PM
No affiliation info available
Heijnen P
No affiliation info available
Hamulyak K
No affiliation info available
Hemker HC
No affiliation info available

MeSH

AdolescentAdultAgedContraceptives, Oral, CombinedDesogestrelFactor VFemaleHemostasisHeterozygoteHumansLevonorgestrelMaleMiddle AgedNorgestrelNorpregnenesProtein CThrombinThrombophlebitis

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

9136971

Citation

Rosing, J, et al. "Oral Contraceptives and Venous Thrombosis: Different Sensitivities to Activated Protein C in Women Using Second- and Third-generation Oral Contraceptives." British Journal of Haematology, vol. 97, no. 1, 1997, pp. 233-8.
Rosing J, Tans G, Nicolaes GA, et al. Oral contraceptives and venous thrombosis: different sensitivities to activated protein C in women using second- and third-generation oral contraceptives. Br J Haematol. 1997;97(1):233-8.
Rosing, J., Tans, G., Nicolaes, G. A., Thomassen, M. C., van Oerle, R., van der Ploeg, P. M., Heijnen, P., Hamulyak, K., & Hemker, H. C. (1997). Oral contraceptives and venous thrombosis: different sensitivities to activated protein C in women using second- and third-generation oral contraceptives. British Journal of Haematology, 97(1), 233-8.
Rosing J, et al. Oral Contraceptives and Venous Thrombosis: Different Sensitivities to Activated Protein C in Women Using Second- and Third-generation Oral Contraceptives. Br J Haematol. 1997;97(1):233-8. PubMed PMID: 9136971.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Oral contraceptives and venous thrombosis: different sensitivities to activated protein C in women using second- and third-generation oral contraceptives. AU - Rosing,J, AU - Tans,G, AU - Nicolaes,G A, AU - Thomassen,M C, AU - van Oerle,R, AU - van der Ploeg,P M, AU - Heijnen,P, AU - Hamulyak,K, AU - Hemker,H C, PY - 1997/4/1/pubmed PY - 1997/4/1/medline PY - 1997/4/1/entrez SP - 233 EP - 8 JF - British journal of haematology JO - Br J Haematol VL - 97 IS - 1 N2 - Epidemiological studies have shown that women who use third-generation oral contraceptives (OC) containing desogestrel, gestodene or norgestimate have a higher risk of venous thrombosis than women who use second-generation OC containing levonorgestrel. It is also known that a mutation in factor V (factor V(Leiden)), which results in resistance to activated protein C (APC) and which is the most common cause of hereditary thrombophilia, potentiates the prothrombotic effect of OC. Effects of APC on thrombin generation in the plasma of women using OC were compared to the response to APC in non-OC users and in individuals that were heterozygous or homozygous for factor V(Leiden). The response towards APC was evaluated on basis of the ratio (APC-sr) of the time integrals of thrombin formation determined in the presence and absence of APC. Compared with women not using OC, women who used OC exhibited a significantly decreased sensitivity to APC (P<0.001), independent of the kind of OC used. Women who used third-generation monophasic OC were significantly less sensitive to APC than women using second-generation OC (P<0.001) and had APC-sr that did not significantly differ from heterozygous female carriers of factor V(Leiden) who did not use OC. Women who were heterozygous for factor V(Leiden) and used OC had APC-sr in the range of homozygous carriers of factor V(Leiden). Two women who started OC therapy had significantly elevated APC-sr within 3 d. Acquired APC resistance may explain the epidemiological observation of increased risk for venous thrombosis in OC users, especially in women using third-generation OC. SN - 0007-1048 UR - https://www.unboundmedicine.com/medline/citation/9136971/Oral_contraceptives_and_venous_thrombosis:_different_sensitivities_to_activated_protein_C_in_women_using_second__and_third_generation_oral_contraceptives_ DB - PRIME DP - Unbound Medicine ER -