Background
Sickle Cell Disease (SCD) is a cause of anemia frequently requiring blood transfusions. Current treatments for Sickle Cell Anemia include Hydroxyurea, or the recently approved medication in 2019, Voxelotor. There are several research studies regarding the prevalence of SCD and gender-related differences in the pediatric population. There is also a study determining gender differences in the pattern of Sickle Cell Anemia complications in the Nigerian population, but data is scarce when related to gender disparities in transfusions on hospitalized patients with Sickle Cell Disease while on Voxelotor or Hydroxyurea. We conducted a retrospective cohort study to evaluate for gender-disparities related to blood transfusions in hospitalized patients with Sickle Cell Disease who were on either taking Voxelotor or Hydroxyurea.

Methods
This retrospective cohort study identified 8,815 patients across several facilities diagnosed with Sickle Cell Disease who were taking outpatient Voxelotor or Hydroxyurea. Patients who had CKD Stage 4 or 5, ESRD, pregnancy, major surgery, normal hemoglobin levels, and elevated liver enzymes were excluded with a final sample of 6,240. Patients were stratified into two groups based on the treatment they were on, a group taking Voxelotor (243 patients 3.92%) and a group taking Hydroxyurea (5961 96.08%) outpatient. We assessed patient’s characteristics such as age, sex, race, smoking status and events during hospitalization. The primary outcome was to evaluate for gender-disparities related to blood transfusions in hospitalized patients with Sickle Cell Disease who were on either taking Voxelotor or Hydroxyurea. Zero-inflated Poisson regression was used to determine the quantity and prediction of blood transfusions required according to these characteristics.

Results
Of the 6,240 with Sickle Cell Disease who were either on Voxelotor or Hydroxyurea the mean age was 31.32 years, 58.11% were female and 41.89% were male, 94.63% were African-American and 5.37% were non-African-Americans. Sex is significantly associated with the log count of transfusions, when controlling for other variables (χ2 = 11.32, p < 0.001). Being female increases the expected number of transfusions by a factor of 0.879 – in other words, being male increases the expected number of transfusions by a factor of 1.138 (1/0.879) irrespective of the medication taken for Sickle Cell Disease.

Conclusion
Being female increases the expected number of blood transfusions when comparing to male sex and other variables (Wald Chi Square 11.32 p<.0008, CI 0.8153~ 0.9475) irrespective of each medication group. Suggested contributing factor is heavy menstrual bleeding during menses leading to worsening anemia and lower baseline hemoglobin and hematocrit levels. However, the limitation is having a relatively small sample size, and possible confounders from the patients and the disease itself. Further research is required to investigate this.

References and Resources

1. Ceglie G, Di Mauro M, Tarissi De Jacobis I, de Gennaro F, Quaranta M, Baronci C, Villani A, Palumbo G. Gender-Related Differences in Sickle Cell Disease in a Pediatric Cohort: A Single-Center Retrospective Study. Front Mol Biosci. 2019 Dec 5;6:140. doi: 10.3389/fmolb.2019.00140. PMID: 31867340; PMCID: PMC6906547.
2. Ugwu, Angela. “Gender differences in the complications of sickle cell anemia.” International Journal of Medicine and Health Development, vol. 27, no. 1, Jan.-Mar. 2022, p. 38. Gale OneFile: Health and Medicine, link.gale.com/apps/doc/A686069123/HRCA?u=anon~f4f69e18&sid=googleScholar&xid=a8f36bf0. Accessed 17 May 2023.
3. ‌V, Akre Charuhas, et al. “Do Gender Differences Influence the Prevalence of Sickle Cell Disorder and Related Morbidities among School Children in Rural Central India?” International Journal of Collaborative Research on Internal Medicine & Public Health, vol. 5, no. 5, 2013, internalmedicine.imedpub.com/do-gender-differences-influence-the-prevalence-of-sicklecell-disorder-and-related-morbidities-among-schoolchildren-in-rural-central-india.php?aid=6300.
4. Ware, Russell E., et al. “Concomitant Hydroxyurea and Voxelotor: Results from the HOPE Study.” Blood, vol. 134, no. Supplement_1, 13 Nov. 2019, pp. 1003–1003, https://doi.org/10.1182/blood-2019-130767. Accessed 2 Jan. 2021.