Progestin-only contraception is first line for sickle cell disease: a comment on “Hormonal therapies in females with blood disorders: thrombophilia, thrombosis, hemoglobinopathies, and anemias.”

To the Editor,

We read Baldwin et al.’s [1] welcome review of “Hormonal therapies in females with blood disorders” and believe strongly that it sells the thrombosis risks associated with sickle cell disease (SCD) short.

The authors state that SCD “may be” associated with an increased thrombosis risk, but the thrombosis risk in SCD is equivalent to other high-risk, inherited thrombophilias [2]. Approximately 12% to 25% of adults with SCD have had a thrombotic event, with a median age at first event between 25 and 30 years, like antithrombin deficiency [2]. Thrombosis is a marker of disease severity associated with decreased overall survival. These realities may have been overlooked by the authors because the most recent citation in the SCD section is from 2012. Evidence establishing SCD as a high-risk thrombophilia emerged in the past decade.

While the authors state that they “adapted and modified” the 2016 Centers for Disease Control and Prevention Medical Eligibility Criteria for Contraceptive Use Guideline (US MEC), they made no adaptations for SCD. The Figure illustrates why this is necessary. The US MEC does not identify SCD as a high-risk thrombogenic mutation. Further, the US MEC relegates SCD to a “sub-condition” of anemia, leaving no space for the addition of common SCD “sub-conditions,” which might further modify contraception recommendations. As shown, other US MEC conditions or subconditions are common in SCD and limit the use of combined hormonal contraception. Other SCD-related thrombosis risk factors are unaddressed in this guideline, such as indwelling catheters or frequent hospitalizations. Even as we await the spring 2024 updates to the US MEC, clinicians can use contemporary data to inform contraceptive recommendations for individuals with SCD [3].

Figure.

The 2016 Centers for Disease Control and Prevention’s Medical Eligibility Criteria for Contraception Guideline approves wide use of estrogen-containing contraception for sickle cell disease (SCD). Subsequent rows illustrate how these recommendations would change if SCD was recognized as a thrombogenic mutation, how the presence of gallbladder disease and other common SCD comorbidities are considered by the Guideline, and how the consideration given to other conditions, such as rheumatoid arthritis, lupus, and cystic fibrosis were not extended to SCD, which is considered a “sub-condition,” obfuscating disease complications that exacerbate high baseline thrombosis risks. Source: Curtis KM, Tepper NK, Jatlaoui TC, Berry-Bibee E, Horton LG, Zapata LB, et al. U.S. Medical Eligibility Criteria for Contraceptive Use, 2016. MMWR Recomm Rep 2016;65:1–103. https://doi.org/10.15585/mmwr.rr6503a1

As SCD is a high-risk thrombophilia, recommendations from other high-risk inherited thrombophilias can be reasonably extended to this population, making progestin-only contraception first-line for people with SCD. This recommendation is consistent with the National Heart, Lung, and Blood Institute’s 2014 Sickle Cell Disease Guidelines and acknowledges the significant thrombosis risks associated with the disease [3]. As with all high-risk thrombophilias, thrombosis risks associated with estrogen-containing hormonal contraception are balanced against the risk of thrombosis in pregnancy. So too people with SCD require individualized, expert care so that contraceptive decisions can be made using the best available evidence in alignment with patients’ preferences and values. Research is needed to define the effects of age, SCD genotype, SCD complications, and SCD treatments on thrombophilic risks associated with exposure to conjugated estrogens. Yet until high-quality data emerge, people with SCD deserve the same nuanced consideration as those with other hypercoagulable conditions.

SCD-specific reproductive health care is a long-standing, neglected, and patient-centered SCD concern. Every mortality risk factor needs consideration as we strive to improve the stagnant life expectancy for adults with SCD. This review’s limitations highlight the urgent need for resources to execute the thoughtful multidisciplinary scholarship and high-quality care our patients deserve.