Venous Thromboembolism in Women of Childbearing Age: Insights from the START Registry

Abstract

Background Women of childbearing age are exposed to venous thromboembolic risk mainly for pregnancy and use of oral contraceptives. The impact of risk factors (RF) on venous thromboembolism (VTE) in these circumstances is still unclear.

Aim In the context of START registry, we aimed to investigate the weight of a series of RF on the occurrence of pregnancy- or combined oral contraceptive (COC)-associated VTE.

Materials and Methods We selected all women included in the START for VTE occurred between 18–42 years and compared those with a first or recurrent pregnancy/postpartum- (group A) or COC-VTE (group B) with those who had VTE outside these circumstances (group C). Final analysis included a cohort of 532 women. Follow-up data showed that there were no significant differences between the groups in terms of thrombotic and haemorrhagic complications. As for pregnancy-associated VTE, the overall outcome was good in terms of both maternal and fetal prognosis.

Results In a binary model of logistic regression, correcting for potential confounders, VTE family history conferred a significant and independent higher risk of COC-VTE compared with group C. Similarly, comparison between group A and C documented that family history significantly affected the risk of pregnancy-associated VTE. VTE in the group C was significantly associated with older age. Lastly, smoke was a significant risk factor for pregnancy/postpartum VTE when group A and group B were compared.

Conclusion Present data suggest that in the setting of fertile women, family history of VTE has a greater role in predicting COC- and pregnancy/postpartum- VTE than outside these circumstances.

Keywords

oral contraceptives - pregnancy - postpartum - venous thromboembolism

Note

The list of START Registry Investigators is available in the [Supplementary Material] (available in the online version).

Publication History

Received: 27 February 2023

Accepted: 25 April 2023

Article published online:
01 June 2023

• References

• 1 Samuelsson E, Hägg S. Incidence of venous thromboembolism in young Swedish women and possibly preventable cases among combined oral contraceptive users. Acta Obstet Gynecol Scand 2004; 83 (07) 674-681
• 2 Lidegaard Ø, Nielsen LH, Skovlund CW, Skjeldestad FE, Løkkegaard E. Risk of venous thromboembolism from use of oral contraceptives containing different progestogens and oestrogen doses: Danish cohort study, 2001-9. BMJ 2011; 343: d6423
• 3 de Bastos M, Stegeman BH, Rosendaal FR. et al. Combined oral contraceptives: venous thrombosis. Cochrane Database Syst Rev 2014; (03) CD010813
• 4 Practice Committee of the American Society for Reproductive Medicine. Electronic address: [e-mail]; Practice Committee of the American Society for Reproductive Medicine. Combined hormonal contraception and the risk of venous thromboembolism: a guideline. Fertil Steril 2017; 107: 43-51
• 5 Abe K, Kuklina EV, Hooper WC, Callaghan WM. Venous thromboembolism as a cause of severe maternal morbidity and mortality in the United States. Semin Perinatol 2019; 43 (04) 200-204
• 6 Virkus RA, Løkkegaard EC, Bergholt T, Mogensen U, Langhoff-Roos J, Lidegaard Ø. Venous thromboembolism in pregnant and puerperal women in Denmark 1995-2005. A national cohort study. Thromb Haemost 2011; 106 (02) 304-309
• 7 Palareti G, Legnani C, Antonucci E. et al. Do women with venous thromboembolism bleed more than men during anticoagulation? Data from the real-life, prospective START-Register. Ther Adv Drug Saf 2021; 12: 20 420986211062965
• 8 Schulman S, Kearon C. Subcommittee on Control of Anticoagulation of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients. J Thromb Haemost 2005; 3 (04) 692-694
• 9 Kaatz S, Ahmad D, Spyropoulos AC, Schulman S. Subcommittee on Control of Anticoagulation. Definition of clinically relevant non-major bleeding in studies of anticoagulants in atrial fibrillation and venous thromboembolic disease in non-surgical patients: communication from the SSC of the ISTH. J Thromb Haemost 2015; 13 (11) 2119-2126
• 10 Blanco-Molina A, Rota LL, Di Micco P. et al; RIETE Investigators. Venous thromboembolism during pregnancy, postpartum or during contraceptive use. Thromb Haemost 2010; 103 (02) 306-311
• 11 Uluduz D, Sahin S, Duman T. et al. Cerebral venous sinus thrombosis in women: subgroup analysis of the VENOST Study. Stroke Res Treat 2020; 2020: 8610903
• 12 Grandone E, Di Micco PP, Villani M. et al; RIETE Investigators. Venous thromboembolism in women undergoing assisted reproductive technologies: data from the RIETE Registry. Thromb Haemost 2018; 118 (11) 1962-1968
• 13 Harbin MM, Lutsey PL. May-Thurner syndrome: History of understanding and need for defining population prevalence. J Thromb Haemost 2020; 18 (03) 534-542
• 14 Villani M, Tiscia GL, Margaglione M. et al. Risk of obstetric and thromboembolic complications in family members of women with previous adverse obstetric outcomes carrying common inherited thombophilias. J Thromb Haemost 2012; 10 (02) 223-228
• 15 Cosmi B, Legnani C, Bernardi F, Coccheri S, Palareti G. Value of family history in identifying women at risk of venous thromboembolism during oral contraception: observational study. BMJ 2001; 322 (7293): 1024-1025
• 16 Vandenbroucke JP, van der M eer FJ, Helmerhorst FM, Rosendaal FR. Family history and risk of venous thromboembolism with oral contraception. Family history is important tool. BMJ 2001; 323 (7315): 752
• 17 Ashraf N, Visweshwar N, Jaglal M, Sokol L, Laber D. Evolving paradigm in thrombophilia screening. Blood Coagul Fibrinolysis 2019; 30 (05) 249-252
• 18 Zöller B, Svensson PJ, Dahlbäck B, Lind-Hallden C, Hallden C, Elf J. Genetic risk factors for venous thromboembolism. Expert Rev Hematol 2020; 13 (09) 971-981
• 19 Cosmi B, Legnani C, Bernardi F, Coccheri S, Palareti G. Role of family history in identifying women with thrombophilia and higher risk of venous thromboembolism during oral contraception. Arch Intern Med 2003; 163 (09) 1105-1109
• 20 Arachchillage DJ, Mackillop L, Chandratheva A, Motawani J, MacCallum P, Laffan M. Thrombophilia testing: A British Society for Haematology guideline. Br J Haematol 2022; 198 (03) 443-458
• 21 Elgendy IY, Gad MM, Mansoor H. et al. Acute pulmonary embolism during pregnancy and puerperium: national trends and in-hospital outcomes. Mayo Clin Proc 2021; 96 (08) 2102-2113
• 22 Ghaji N, Boulet SL, Tepper N, Hooper WC. Trends in venous thromboembolism among pregnancy-related hospitalizations, United States, 1994-2009. Am J Obstet Gynecol 2013; 209 (05) 433.e1-433.e8
• 23 Krenitsky N, Friedman AM, Yu K. et al. Trends in venous thromboembolism and associated risk factors during delivery hospitalizations from 2000 to 2018. Obstet Gynecol 2022; 139 (02) 223-234
• 24 Brenner B, Grandone E, Makatsariya A, Khizroeva J, Bitsadze V, Tretyakova M. Approach to the evaluation and treatment of venous thromboembolism in pregnancy. Semin Reprod Med 2021; 39 (5–06): 186-193
• 25 Bikdeli B, Muriel A, Wang Y. et al. Sex differences in patients characteristics, risk factors, and symptomatology in older adults with pulmonary embolism: findings from the SERIOUS-PE Study. Semin Thromb Haemost 2023; 49 (07) 725-735
• 26 Piazza G, Grandone E. Thrombophilia, Antithrombotic Therapy, and Recurrent Pregnancy Loss: A Call for Pragmatism in the Face of Unknowns. Semin Reprod Med 2021; 39 (5–06): 167-169