[Effects of second and third generation oral contraceptives on hemostasis].
Use of oral contraceptives induce changes in haemostatic parameters: changes occur in the procoagulant, anticoagulant, and fibrinolytic systems. The increased risk of venous thromboembolism with use of third, as compared with second generation oral contraceptives, found in epidemiological studies, has stimulated new research in haemostatic changes induced by both generations of oral contraceptives. A randomized crossover study showed that use of the third generation pill caused a greater increase of factor VII and prothrombin and a more pronounced decrease of factor V than the second generation pill. Acquired resistance to activated protein C (APC) was induced more strongly by preparations of the third than by those of the second generation. The concentration of protein S decreased markedly exclusively during use of the third generation pill, while it did not change during use of the second generation pill. The oral contraception-related effects on the anticoagulant system strongly resemble those of some forms of hereditary thrombophilia. If a woman with hereditary APC resistance (caused by factor V Leiden) uses oral contraceptives as well, and especially when she uses those of the third generation, she is subject to a considerable increase of the risk of venous thrombosis and becomes even more resistant to the anticoagulant action of protein C. In view of the epidemiological backgrounds of the difference in risk of thrombosis between second and third generation contraceptives, the second generation pill is recommended as the first choice for oral contraception.
Middeldorp
S
S
Academisch Medisch Centrum, afd. Vasculaire Geneeskunde, Postbus 22.660, 1100 DD Amsterdam. s.middeldorp@amc.uva.nl
Rosing
J
J
Bouma
B N
BN
Büller
H R
HR
D020016:Activated Protein C Resistance / Q000150:complications; D001779:Blood Coagulation Factors / Q000187:drug effects*; D020147:Coagulation Protein Disorders / Q000150:complications*; D003276:Contraceptives, Oral / Q000009:adverse effects* / Q000145:classification; D000075202:Contraindications; D018592:Cross-Over Studies; D005165:Factor V / Q000187:drug effects; D005167:Factor VII / Q000187:drug effects; D005260:Female; D006487:Hemostasis / Q000187:drug effects*; D006801:Humans; D009426:Netherlands; D017410:Practice Guidelines as Topic; D017293:Protein S / Q000187:drug effects; D011516:Prothrombin / Q000187:drug effects; D016032:Randomized Controlled Trials as Topic; D020246:Venous Thrombosis / Q000139:chemically induced / Q000517:prevention & control*
D001779:Blood Coagulation Factors; D003276:Contraceptives, Oral; D017293:Protein S; D005165:Factor V; D005167:Factor VII; D011516:Prothrombin