By Jeffrey T. Jensen, MD, MPH, Editor
Leon Speroff Professor and Vice Chair for Research, Department of Obstetrics and Gynecology, Oregon Health & Science University, Portland
Dr. Jensen reports that he is a consultant for and receives grant/research support from Bayer, Merck, ContraMed, and FHI360; he receives grant/research support from Abbvie, HRA Pharma, Medicines 360, and Conrad; and he is a consultant for the Population Council.
Women experience a two-fold increase in risk of venous thrombosis (relative to nonpregnant women) following induced abortion, but a more than six-fold overall reduction in risk of thrombosis compared to women who continue the pregnancy to term.
Liu N, Vigod SN, Farrugia MM, et al. Venous thromboembolism after induced abortion: A population-based, propensity-score-matched cohort study in Canada. Lancet Haematol 2018;5:e279-e288.
We know that pregnancy increases the risk of thromboembolic disorders, but few researchers have evaluated the risks associated with abortion specifically. To close this knowledge gap, Liu et al used data available from the universal healthcare system of Ontario, Canada, where all healthcare, including access to abortion and obstetrics services, receives public funding. Health outcomes recorded in several databases were linked by unique patient identifiers. For this analysis, the authors identified all primigravid women aged 15-49 years who had an induced abortion (< 20 weeks’ gestation) between Jan. 1, 2003, and Dec. 31, 2015. They then used a propensity score to match patients to primigravid women who had a live birth (1:1 match) or nulligravid women who were not pregnant on the procedure date of the matched counterpart and who did not conceive within one year afterward (5:1 match). Liu et al defined the index date as the induced abortion procedure date for the induced abortion group and the matched nonpregnant group, and the delivery date for the live birth group. The authors generated hazard ratios (HRs) of the 42-day risk of venous thromboembolism (VTE) after the index date using Cox proportional hazard models. They confined the analysis to primigravid women to avoid the inclusion of more than one pregnancy per woman during the study period and to minimize the influence of previous pregnancy events (e.g., VTE) on the therapeutic decision-making (e.g., prophylactic anticoagulation or the decision to terminate the pregnancy) in the index pregnancy.
The authors identified 176,001 cases of induced abortion during the study interval, and propensity-matched these to 880,005 nonpregnant women and 176,001 primigravid women in the live birth group. Propensity matching was effective, with standardized differences of < 0.1 for all covariates.
Compared to the matched nonpregnant group (incidence rate, 14 per 100,000 women), women in the induced abortion group experienced a more than two-fold increase in VTE (30 per 100,000; HR, 2.23; 95% confidence interval [CI], 1.61-3.08). Not surprisingly, women who underwent abortion at early gestational ages (< 15 weeks) had a lower incidence of VTE (27 per 100,000) than women at ≥ 15 weeks (136 per 100,000). The highest risk of VTE was seen among the live birth group (185 per 100,000). In comparison to this live birth group, women undergoing induced abortion had a six-fold reduction in VTE (HR, 0.16; 95% CI, 0.12-0.22). In a separate analysis, the authors compared the incidence of VTE in the 42 days following the index date among an induced abortion subgroup with known exact gestational age to the incidence of VTE observed in the 42 days from the same index gestational age among the matched live birth group counterparts and found no significant difference (HR, 1.29; 95% CI, 0.64-2.59). All of these effects are consistent with prior research that supports an increasing risk of VTE with advancing gestational age.
The authors concluded that the risk of VTE increases during pregnancy, regardless of how the pregnancy ends, and suggested that testing for VTE and the provision of VTE prophylaxis should apply both to women who undergo termination of pregnancy or continue to term.
COMMENTARY
I sometimes fantasize that data demonstrating the safety of abortion somehow will influence the political debate. While this paper may not move the needle of public opinion, it should influence the way clinicians evaluate the risks and benefits associated with contraception care and pregnancy.
First, consider the known risks associated with VTE. The overall risk of VTE for women without a positive family history, other identifiable risk factors, or known thrombophilia is low. It is well-established that both pregnancy and estrogen-containing contraceptives increase the risk of VTE.1 The risk appears to be related to circulating estrogen levels and likely evolved as a life-saving adaptive strategy for female mammals in response to pregnancy. Potent synthetic estrogens like ethinyl estradiol and the first-pass effects after oral administration of any estrogens mimic the hepatic stimulation seen during pregnancy. In contrast, transdermal administration of estradiol in postmenopausal women does not increase VTE risk.2
Inherited thrombophilias increase the baseline risk of VTE and also interact with other known risk factors, such as pregnancy and combined hormonal contraception (CHC).3 For this reason, both the Centers for Disease Control and Prevention and the World Health Organization provide a Category 4 (unacceptable risk) rating for CHC in women carrying a known mutation. Although a personal history of VTE also carries a Category 4 recommendation, a family history of VTE in a first-degree relative is only a Category 2 (advantages generally outweigh risks). Routine testing for known thrombophilias in women with a positive family history is not recommended because of cost and low yield.4 There is no Medical Eligibility Criteria for pregnancy, but providers should consider applying similar recommendations against pregnancy for women with Category 3 or 4 recommendations for estrogen-containing contraceptives.
Liu et al provided important new data demonstrating the risk of VTE associated with abortion care before 20 weeks. The bottom line: an overall two-fold increase in risk relative to nonpregnant woman, and a six-fold reduction in risk compared to women who continue pregnancy to live birth. The two-fold increase in risk was similar to the risk associated with the use of combined oral contraceptives.5,6 In other words, if non-use of a combined method because of concern over VTE risk resulted in an unintended pregnancy and abortion, the overall increase in VTE risk was about the same. Should the woman decide to continue the pregnancy to term, the risk of VTE increases dramatically, comparing rates from the Canadian study, in which there was a 13-fold (RR, 13.2) increase over the nonpregnant cohort.
The takeaway point is that clinicians should strongly consider risk factors for VTE in abortion patients and consider prophylaxis and treatment as indicated. However, the subgroup analysis finding no difference in the risk of VTE in the 42 days following the index abortion date to the same gestational time interval in women continuing their pregnancy strongly supports that the abortion itself is not an independent risk factor for VTE. These data demonstrated that the VTE risk increased with gestational age.
REFERENCES
- Rosendaal FR, Van Hylckama Vlieg A, Tanis BC, Helmerhorst FM. Estrogens, progestogens and thrombosis. J Thromb Haemost 2003;1:1371-1380.
- Canonico M, Oger E, Plu-Bureau G, et al. Hormone therapy and venous thromboembolism among postmenopausal women: Impact of the route of estrogen administration and progestogens: The ESTHER study. Circulation 2007;115:840-845.
- Bergendal A, Persson I, Odeberg J, et al. Association of venous thromboembolism with hormonal contraception and thrombophilic genotypes. Obstet Gynecol 2014;124:600-609.
- Creinin MD, Lisman R, Strickler RC. Screening for factor V Leiden mutation before prescribing combination oral contraceptives. Fertil Steril 1999;72:646-651.
- Dinger J, Mohner S, Heinemann K. Cardiovascular risk associated with the use of an etonogestrel-containing vaginal ring. Obstet Gynecol 2013;122:800-808.
- Dinger J, Bardenheuer K, Heinemann K. Cardiovascular and general safety of a 24-day regimen of drospirenone-containing combined oral contraceptives: Final results from the International Active Surveillance Study of Women Taking Oral Contraceptives. Contraception 2014;89:253-263.
