Disease Status Influences VTE Risk in Women with Sickle Cell Disease

Erica M. Sparkenbaugh, PhD

Credit: The University of North Carolina at Chapel Hill

A single-center retrospective study found the risk of venous thromboembolism (VTE) is likely influenced by disease status rather than estrogen-containing hormonal contraception exposure among women with sickle cell disease (SCD).¹

Contraception use and VTE status were assessed in nearly 400 women with SCD between 2010 and 2022, with data revealing a nonsignificant adjusted odds ratio (OR) between contraception and the risk of VTE in this population.

“The study’s results thus highlight the unique considerations and risk profiles associated with contraception in women with SCD, underscoring the importance of tailored medical care for this patient population,” wrote the investigative team, led by Erica M. Sparkenbaugh, PhD, pathology and laboratory medicine, The University of North Carolina at Chapel Hill.

Individuals with SCD experience an increased risk of VTE, with an incidence rate between 14% and 25%, and the likelihood is higher in women than men with SCD.² Known risk factors for VTE in women with SCD include disease severity, defined by the frequency of hospitalization and vaso-occlusive crises (VOCs).

Given the high vulnerability of women with SCD to VTE, various factors are considered when initiating a contraceptive method. Contraceptive use guidelines from 2016 cited no current restrictions on progesterone-only contraception in SCD and considered estrogen-containing safe, as the benefits were believed to outweigh the risks.³

However, sickle cell providers have previously expressed concerns that estrogen-containing contraception could compound VTE risk in women with SCD.⁴ According to Sparkenbaugh and colleagues, this study sought to define the VTE risks associated with different hormonal contraception methods, to facilitate informed decision-making for individual patients.¹

Investigators reviewed all data collected on women of reproductive age (15–49 years) with a diagnosis of SCD over 12 years at their institution. Data on thrombosis development at any time, the presence and type of contraception, presence and type of VTE, and confounders, including age, SCD genotype, and severity of SCD were additionally recorded.

A total of 370 women with SCD were identified, with an average age of 32.71 years at data extraction. Of this population, 93 (25.1%) had a history of VTE, including 35 (37.6%) with deep vein thrombosis (DVT) and 41 (44.1%) with pulmonary embolism (PE).

Overall, 219 (59.2%) women utilized hormonal contraception at any time point. Among total contraception users, 73 of 219 (33.3%) experienced a VTE at any point, while 38 of 184 (20.6%) experienced VTE while actively using contraception. By contrast, only 20 of 151 (13.2%) women never exposed to hormonal contraception experienced a VTE.

Among those exposed to hormonal contraception, 64 of 184 (34.7%) were on estrogen-containing contraception, and 120 of 184 (65.3%) used progestin-only formulations. After Cox regression analysis, investigators found progestin-only formulations increased VTE risk (hazard ratio [HR], 2.03; 95% CI, 1.107–3.726; P <.05). Upon accounting for disease severity, the team noted the association between progestin-only treatment and VTE risk was not significant.

Further analysis revealed both severe (odds ratio [OR], 11.79; 95% CI, 5.14–27.06; P <.001) and moderate (OR, 4.37; 95% CI, 1.77–10.76; P = .001) disease-elevated VTE risk, in comparison with mild disease. However, genotype nor hydroxyurea had any influence on VTE risk.

For a more detailed understanding of the risk associated with estrogen-containing HC in SCD, Sparkenbaugh emphasized the need for further studies with larger sample sizes. The team also advocated for contraception status as a necessary data point in large nationwide patient databases.

“Clinicians should consider these findings and those previously published when discussing reproductive care in women with SCD,” they wrote. “It is still imperative to address the question of why women with SCD have a higher risk of VTE and if there is a synergistic effect between estrogen-containing HC and disease severity on VTE risk.”

References

1. _{Light J, Abrams CM, Ilich A, et al. Disease severity drives risk of venous thrombotic events in women with sickle cell disease in a single-center retrospective study. Res Pract Thromb Haemost. 2024;8(4):102471. Published 2024 Jun 10. doi:10.1016/j.rpth.2024.102471}
2. _{Noubiap JJ, Temgoua MN, Tankeu R, Tochie JN, Wonkam A, Bigna JJ. Sickle cell disease, sickle trait and the risk for venous thromboembolism: a systematic review and meta-analysis. Thromb J. 2018;16:27. Published 2018 Oct 4. doi:10.1186/s12959-018-0179-z}
3. _{Curtis KM, Tepper NK, Jatlaoui TC, et al. U.S. Medical Eligibility Criteria for Contraceptive Use, 2016. MMWR Recomm Rep. 2016;65(3):1-103. Published 2016 Jul 29. doi:10.15585/mmwr.rr6503a1}
4. _{Roe AH, Lang B, McAllister A, et al. Contraceptive use and preferences among females with sickle cell disease. Contraception. 2022;105:42-45. doi:10.1016/j.contraception.2021.08.009}