Abstract
OBJECTIVE
The object of the study was to determine the effects of oral contraceptives on blood coagulation, in particular on the protein C pathway.
STUDY DESIGN
Plasma samples from healthy men, from healthy female users and nonusers of oral contraceptives, and from heterozygous and homozygous male and female carriers of the factor V Leiden mutation (some of whom used oral contraceptives) were tested for their sensitivity to activated protein C by means of a new activated protein C resistance test developed in our laboratory. This assay is based on measurement of the effect of activated protein C on the endogenous thrombin potential, the time integral of thrombin generation initiated in plasma through the extrinsic coagulation pathway.
RESULTS
The normalized activated protein C sensitivity ratio ([ETP+APC/ETP-APC]plasma/[ETP+APC/ETP-APC]normal plasma, where ETP is endogenous thrombin potential, +APC is with activated protein C, and -APC is without activated protein C) of men was lower than that of healthy female nonusers of oral contraceptives. The normalized activated protein C sensitivity ratio of the users of oral contraceptives was significantly higher than that of nonusers of oral contraceptives. The normalized activated protein C sensitivity ratio of women who were using oral contraceptives with third-generation progestogens was higher than that of users of oral contraceptives with second-generation progestogens. Furthermore, the normalized activated protein C sensitivity ratio of 80% of the users of third-generation preparations fell within the 5th to 95th percentile of the normalized activated protein C sensitivity ratio of female carriers of factor V Leiden, a mutation that is associated with hereditary resistance to activated protein C and with an increased risk of venous thromboembolism.
CONCLUSION
Acquired activated protein C resistance may explain the increased risk of venous thromboembolism among users of oral contraceptives reported in epidemiologic studies and the higher risk of venous thromboembolism among users of oral contraceptives with third- versus second-generation progestogens.
TY - JOUR
T1 - Effects of oral contraceptives on hemostasis and thrombosis.
AU - Rosing,J,
AU - Tans,G,
PY - 1999/6/16/pubmed
PY - 1999/6/16/medline
PY - 1999/6/16/entrez
KW - Biology
KW - Blood Coagulation Effects--women
KW - Blood Proteins--women
KW - Clinical Research
KW - Contraception
KW - Contraceptive Agents
KW - Contraceptive Agents, Female
KW - Contraceptive Agents, Progestin
KW - Contraceptive Methods
KW - Developed Countries
KW - Diseases
KW - Embolism
KW - Europe
KW - Family Planning
KW - Hematological Effects
KW - Hemic System
KW - Literature Review
KW - Netherlands
KW - Oral Contraceptives
KW - Physiology
KW - Research Methodology
KW - Thromboembolism--women
KW - Vascular Diseases
KW - Western Europe
KW - Women
SP - S375
EP - 82
JF - American journal of obstetrics and gynecology
JO - Am J Obstet Gynecol
VL - 180
IS - 6 Pt 2
N2 - OBJECTIVE: The object of the study was to determine the effects of oral contraceptives on blood coagulation, in particular on the protein C pathway. STUDY DESIGN: Plasma samples from healthy men, from healthy female users and nonusers of oral contraceptives, and from heterozygous and homozygous male and female carriers of the factor V Leiden mutation (some of whom used oral contraceptives) were tested for their sensitivity to activated protein C by means of a new activated protein C resistance test developed in our laboratory. This assay is based on measurement of the effect of activated protein C on the endogenous thrombin potential, the time integral of thrombin generation initiated in plasma through the extrinsic coagulation pathway. RESULTS: The normalized activated protein C sensitivity ratio ([ETP+APC/ETP-APC]plasma/[ETP+APC/ETP-APC]normal plasma, where ETP is endogenous thrombin potential, +APC is with activated protein C, and -APC is without activated protein C) of men was lower than that of healthy female nonusers of oral contraceptives. The normalized activated protein C sensitivity ratio of the users of oral contraceptives was significantly higher than that of nonusers of oral contraceptives. The normalized activated protein C sensitivity ratio of women who were using oral contraceptives with third-generation progestogens was higher than that of users of oral contraceptives with second-generation progestogens. Furthermore, the normalized activated protein C sensitivity ratio of 80% of the users of third-generation preparations fell within the 5th to 95th percentile of the normalized activated protein C sensitivity ratio of female carriers of factor V Leiden, a mutation that is associated with hereditary resistance to activated protein C and with an increased risk of venous thromboembolism. CONCLUSION: Acquired activated protein C resistance may explain the increased risk of venous thromboembolism among users of oral contraceptives reported in epidemiologic studies and the higher risk of venous thromboembolism among users of oral contraceptives with third- versus second-generation progestogens.
SN - 0002-9378
UR - https://www.unboundmedicine.com/medline/citation/10368524/Effects_of_oral_contraceptives_on_hemostasis_and_thrombosis_
L2 - https://linkinghub.elsevier.com/retrieve/pii/S0002-9378(99)70699-X
DB - PRIME
DP - Unbound Medicine
ER -
