Protein C and protein S deficiencies are associated with increased risk of deep vein thrombosis in pregnant women using oral contraceptives.
Journal
Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis
ISSN: 1473-5733
Titre abrégé: Blood Coagul Fibrinolysis
Pays: England
ID NLM: 9102551
Informations de publication
Date de publication:
01 Oct 2023
01 Oct 2023
Historique:
medline:
23
10
2023
pubmed:
19
9
2023
entrez:
19
9
2023
Statut:
ppublish
Résumé
Oral contraceptives are commonly taken by women and are known to increase the risk of venous thromboembolism (VTE). 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). 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. 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. 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.
Sections du résumé
BACKGROUND
BACKGROUND
Oral contraceptives are commonly taken by women and are known to increase the risk of venous thromboembolism (VTE).
OBJECTIVE
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
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
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
CONCLUSIONS
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.
Identifiants
pubmed: 37724475
doi: 10.1097/MBC.0000000000001252
pii: 00001721-990000000-00100
doi:
Substances chimiques
Contraceptives, Oral
0
Desogestrel
81K9V7M3A3
Protein C
0
Antithrombins
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
446-450Informations de copyright
Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.
Références
Galanaud J-P, Sevestre M-A, Pernod G, Genty C, Richaud C, Rolland C, et al. Epidemiology and 3-year outcomes of combined oral contraceptive-associated distal deep vein thrombosis. Res Pract Thromb Haemost 2020; 4:1216–1223.
Heit JA. Epidemiology of venous thromboembolism. Nat Rev Cardiol England 2015; 12:464–474.
Hugon-Rodin J, Horellou M-H, Conard J, Flaujac C, Gompel A, Plu-Bureau G. First venous thromboembolism and hormonal contraceptives in young French women. Medicine (Baltimore) 2017; 96:e7734.
Moiz B. A review of hemostasis in normal pregnancy and puerperium. Natl J Heal Sci 2017; 2:123–127.
Alsheef MA, Alabbad AM, Albassam RA, Alarfaj RM, Zaidi ARZ, Al-Arfaj O, et al. Pregnancy and venous thromboembolism: risk factors, trends, management, and mortality. Biomed Res Int 2020; 4071892.
Trenor CC, Chung RJ, Michelson AD, Neufeld EJ, Gordon CM, Laufer MR, et al. Hormonal contraception and thrombotic risk: a multidisciplinary approach. Pediatrics 2011; 127:347–357.
Saboor M, Moinuddin. In: Saboor MM, editor. Hematology for the undergraduates. 1st ed. Higher Education Commission-Pakistan; 2015.
Cooper DB, Patel P, Mahdy H. Oral contraceptive pills. Treasure Island (FL); 2022.
Abdalhabib EK, Alfeel A, Ali EI, Ibrahim IK, Mobarki AA, Dobie G, et al. Risk factors of venous thromboembolism in sudanese pregnant women. Balkan J Med Genet Poland 2021; 24:49–54.
Abdalhabib EK, Jackson DE, Alzahrani B, Elfaki E, Hamza A, Alanazi F, et al. Assessment of risk factors for deep vein thrombosis associated with natural anticoagulants and fibrinolytic regulatory proteins. Blood Coagul fibrinolysis England 2022; 33:149–152.
Heit JA, Kobbervig CE, James AH, Petterson TM, Bailey KR, Melton LJ 3rd. Trends in the incidence of venous thromboembolism during pregnancy or postpartum: a 30-year population-based study. Ann Intern Med 2005; 143:697–706.
Middeldorp S, Meijers JC, van den Ende AE, van Enk A, Bouma BN, Tans G, et al. Effects on coagulation of levonorgestrel- and desogestrel-containing low dose oral contraceptives: a cross-over study. Thromb Haemost 2000; 84:4–8.
Keenan L, Kerr T, Duane M, Van Gundy K. Systematic review of hormonal contraception and risk of venous thrombosis. Linacre Q 2018; 85:470–477.
Lidegaard O, Nielsen LH, Skovlund CW, Løkkegaard E. Venous thrombosis in users of nonoral hormonal contraception: follow-up study, Denmark 2001−10. BMJ 2012; 344:e2990.
van Vlijmen EFW, Veeger NJGM, Middeldorp S, Hamulyák K, Prins MH, Büller HR, et al. Thrombotic risk during oral contraceptive use and pregnancy in women with factor V Leiden or prothrombin mutation: a rational approach to contraception. Blood 2011; 118:2055–2061. quiz 2375.
Dragoman MV, Tepper NK, Fu R, Curtis KM, Chou R, Gaffield ME. A systematic review and meta-analysis of venous thrombosis risk among users of combined oral contraception. Int J Gynaecol Obstet 2018; 141:287–294.
Stocco B, Fumagalli HF, Franceschini SA, Martinez EZ, Marzocchi-Machado CM, de Sá MFS, et al. Comparative study of the effects of combined oral contraceptives in hemostatic variables: an observational preliminary study. Medicine (Baltimore) 2015; 94:e385.
Gialeraki A, Valsami S, Pittaras T, Panayiotakopoulos G, Politou M. Oral contraceptives and HRT risk of thrombosis. Clin Appl Thromb 2018; 24:217–225.
Van Vlijmen EFW, Brouwer JLP, Veeger NJGM, Eskes TKAB, De Graeff PA, Van Der Meer J. Oral contraceptives and the absolute risk of venous thromboembolism in women with single or multiple thrombophilic defects: results from a retrospective family cohort study. Arch Intern Med 2007; 167:282–289.
Hoffman R, Brenner B. Thrombophilia related issues in women and children. Semin Thromb Hemost 2005; 31:97–103.
Martinelli I, Mannucci PM, De Stefano V, Taioli E, Rossi V, Crosti F, et al. Different risks of thrombosis in four coagulation defects associated with inherited thrombophilia: a study of 150 families. Blood 1998; 92:2353–2358.
Plu-Bureau G, Maitrot-Mantelet L, Hugon-Rodin J, Canonico M. Hormonal contraceptives and venous thromboembolism: an epidemiological update. Best Pract Res Clin Endocrinol Metab 2013; 27:25–34.
Tormene D, Campello E, Simion C, Poretto A, Prandoni P, Simioni P. Combined oral contraceptives and the risk of venous thromboembolism carriers of antithrombin, protein C or S deficiency: sub-analysis of a prospective cohort study. Bleeding Thromb Vasc Biol 2022; 1.
Van Vliet HAAM, Bertina RM, Dahm AEA, Rosendaal FR, Rosing J, Morten Sandset P, et al. Different effects of oral contraceptives containing different progestogens on protein S and tissue factor pathway inhibitor. J Thromb Haemost 2008; 6:346–351.
Tans G, Curvers J, Middeldorp S, Thomassen MC, Meijers JC, Prins MH, et al. A randomized cross-over study on the effects of levonorgestrel- and desogestrel-containing oral contraceptives on the anticoagulant pathways. Thromb Haemost 2000; 84:15–21.
H.S.. Group TOC. The effects of seven monophasic oral contraceptive regimens on hemostatic variables: conclusions from a large randomized multicenter study. Contraception 2003; 67:173–185.