Background: Up to 30% of reproductive-age women experience heavy menstrual bleeding, negatively affecting quality of life. Estrogen-containing contraceptives and antifibrinolytics are first-line treatments. Despite proven efficacy and safety of these agents, plus the use of antifibrinolytics in other high-estrogen states such as post-partum, prescribers are frequently uncomfortable prescribing them in combination due to theoretical thrombotic risk.

Aims: To systematically evaluate the literature exploring the combined effect of pharmacologic or high physiologic estrogen and antifibrinolytics on thromboembolism risk in reproductive-age women when used for heavy menstrual or post-partum bleeding.

Methods: Medline, EMBASE, CINAHL, and Scopus were searched from inception to July 2020. Included articles’ references were screened and a grey literature search was conducted. English language studies exploring the risk of thromboembolism in reproductive-age women prescribed antifibrinolytics alongside estrogen-containing contraceptives or with physiologic high-estrogen states were included. Screening and data abstraction were performed by two independent reviewers (DM, DL) and conflicts were adjudicated by a third reviewer (MS).

Results: A total of 2389 title and abstracts were identified. 33 studies with 27933 participants were extracted for full-text review. 31 studies investigated antifibrinolytic use for post-partum bleeding: 22 randomized controlled trials, 3 retrospective cohort studies, 1 combined prospective-retrospective cohort study, 2 case series, and 3 case reports. Almost all (29/31) studies found no increased thromboembolism risk/rate. However, only 4 studies were powered to make this assessment. The 2 studies describing thromboembolism with post-partum antifibrinolytic use were a case report and case series (N=18), respectively. Only 2 case reports described thromboembolism with concomitant estrogen-containing contraceptives and antifibrinolytic use, both of which reported thromboembolism in women using both agents for < 3 months.

Conclusions: We found no evidence that antifibrinolytic use in high physiologic or pharmacologic estrogenic states results in higher rates of thromboembolism. Prospective studies are warranted to provide an accurate assessment of risk and inform prescribing practices.

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ISTH Congress Abstracts - https://abstracts.isth.org/abstract/a-major-knowledge-gap-in-womens-health-the-combined-effect-of-antifibrinolytics-and-estrogen-on-risk-of-thromboembolism-a-scoping-review/