Evaluating the combined effect of antifibrinolytics and estrogen on the risk of thromboembolism: a scoping review
Bibliographic record
Abstract
BACKGROUND: Up to 30% of reproductive-aged women seek medical attention for heavy menstrual bleeding (HMB). Estrogen-containing contraceptives and antifibrinolytics are first-line treatments. Despite evidence for these agents for HMB and for antifibrinolytics in other high-estrogen states (eg, postpartum), many antifibrinolytic monographs warn against use with concurrent estrogen-containing contraception given theoretical thromboembolic risk. OBJECTIVES: This study aimed to systematically evaluate the literature that explores the combined effect of pharmacologic or high physiologic estrogen and antifibrinolytic agents on thromboembolic risk in women of reproductive age when used for heavy menstrual or postpartum bleeding. METHODS: A systematic literature search was performed of records until April 2023. Publications written in English describing risk or reported cases of thromboembolism in reproductive-age women prescribed antifibrinolytics with estrogen-containing contraceptives or with a physiologic estrogenic state were included. RESULTS: We identified 4302 publications; 55 publications with 199 228 participants were included. Two case reports and one case series described thromboembolism with concomitant estrogen-containing contraceptives and antifibrinolytic use. Four of 5 patients in the case series had other thrombotic risk factors. Fifty-two publications investigated antifibrinolytic use postpartum. Four RCTs of postpartum antifibrinolytic use assessed thromboembolism as a secondary outcome, none of which reported increased risk with antifibrinolytics. One case report suggested possible thrombotic risk wherein the patient had other provoking risk factors. CONCLUSION: We found no strong evidence that intermittent antifibrinolytic use in physiologic estrogenic states is associated with increased reported cases or risk of thromboembolic events. Prospective studies are warranted to assess the thrombotic risk of combined estrogen-containing contraceptives and antifibrinolytics.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.003 | 0.012 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.007 | 0.006 |
| Bibliometrics | 0.004 | 0.004 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.002 | 0.001 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.002 | 0.001 |
| Insufficient payload (model declined to judge) | 0.005 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".