Disease severity drives risk of venous thrombotic events in women with sickle cell disease in a single-center retrospective study

Abstract

Background: Estrogen-containing hormonal contraception (HC) is a well-established risk factor for venous thromboembolism (VTE). Women with sickle cell disease (SCD) also have an increased risk of VTE. However, it is unknown if exposure to HC exacerbates the risk of VTE in women with SCD. Objectives: Assess the impact of HC on VTE risk in women with SCD and explore additional risk factors contributing to VTE development. Methods: We analyzed a retrospective cohort of women of reproductive age (15-49 years) with SCD at the University of North Carolina from 2010 to 2022. Results: We identified 370 women with SCD, and 93 (25.1%) had a history of VTE. Among 219 women exposed to HC, 38 of 184 (20.6%) had a VTE while actively using HC, whereas 20 of 151 (13.2%) women never exposed to HC had a VTE. Of the patients exposed to HC, 64 of 184 (34.7%) were on estrogen-containing HC, with 120 of 184 (65.3%) using progestin-only formulations. Cox regression analysis found that progestin-only formulations increased VTE risk (hazard ratio: 2.03; 95% CI: 1.107-3.726, P < .05). However, when accounting for disease severity, the association between progestin-only treatment and VTE risk was not significant. Indeed, a nuanced analysis revealed that both severe (odds ratio: 11.79; 95% CI: 5.14-27.06; P < .001) and moderate (odds ratio: 4.37; 95% CI: 1.77-10.76; P = .001) disease increased risk compared with mild disease. Neither genotype nor hydroxyurea use influenced VTE risk. Conclusion: Overall, we found that increased thrombotic risk is more likely influenced by disease status than HC exposure and should play a role in shared decision-making with patients.

Keywords

• contraception
• estrogen-containing contraception
• progesterone-only contraception
• pulmonary embolism
• sickle cell disease
• venous thrombosis