Protein C and protein S deficiencies are associated with increased risk of deep vein thrombosis in pregnant women using oral contraceptives

Blood Coagul Fibrinolysis. 2023 Oct 1;34(7):446-450. doi: 10.1097/MBC.0000000000001252. Epub 2023 Sep 12.


Background: Oral contraceptives are commonly taken by women and are known to increase the risk of venous thromboembolism (VTE).

Objective: The aim of this study was to investigate the association between oral contraceptive use and natural anticoagulants, that is, protein C (PC), protein S (PS), and antithrombin in pregnant women with deep vein thrombosis (DVT).

Materials and methods: This case-control study was conducted on 330 pregnant women, that is, cases 165 (who used oral contraceptives) and controls 165 (who did not use oral contraceptives). The levels of PC, PS, and antithrombin were measured and compared between the two groups. The use of different types of oral contraceptives and their association with DVT and PC and PS were also analyzed.

Results: The study found that women with DVT had significantly lower levels of PC and PS compared with controls ( P < 0.001). However, no significant difference was found in the levels of AT. Among the different types of oral contraceptives, first-generation progestin pills including Ethynodiol Diacetate, Norethindrone Acetate, Norethynodrel, and second-generation oral contraceptives (Lynestrenol, Levonorgestrel and Norgestrel) were not found to be associated with lower levels of PC and AT while Desogestrel, Norgestimate, and Gestodene (third-generation) were associated with lower levels of PS.

Conclusion: This study suggests that the use of contraceptives, particularly those containing Desogestrel, Norgestimate, and Gestodene, may be associated with a higher risk of thrombosis because of the associated lower levels of PS. Monitoring anticoagulant levels is crucial in preventing DVT in this population.

MeSH terms

  • Antithrombins
  • Case-Control Studies
  • Contraceptives, Oral / adverse effects
  • Desogestrel / adverse effects
  • Female
  • Humans
  • Pregnancy
  • Pregnant Women
  • Protein C
  • Protein S Deficiency*
  • Venous Thrombosis* / etiology


  • Contraceptives, Oral
  • Desogestrel
  • Protein C
  • Antithrombins