Hidden Dangers: Pulmonary Embolism Risk in Sickle Cell Trait – Insights from the NIS Database 2020

Background: Sickle cell trait is a genetic condition that occurs when an individual inherits a gene for normal hemoglobin (HbA) and a gene for sickle hemoglobin (HbS). Patients are usually asymptomatic and are diagnosed through screening tests followed by genetic analyses. In this study, we aim to compare the incidence of PE in patients with sickle trait and those without it to determine if sickle cell trait increased the risk of development of PE.

Methods: We conducted a retrospective analysis of the NIS database 2020 with an International Classification of Diseases (ICD)-10 code for sickle cell trait, PE and other comorbid conditions. STATA version SE 18.0 was used for statistical analysis. We used multivariate logistic regression models adjusting for demographic characteristics and comorbidities to determine the odds of developing PE in patients with sickle cell trait in comparison to those without it.

Results: During our study period, we noted a total number 31,766,068 hospitalizations out of which sickle cell trait hospitalizations accounted for 56,195. The median age of patients with sickle cell trait hospitalizations was 35.6 years (95% CI 35.05-36.33) and there was a female predominance. 56.39% of the patients with a sickle cell trait related hospitalization had a Charlson Comorbidity Index (CCI) of 56.39%, 17.75% had a CCI 1, 7.48% had a CCI of 2 and 18.38% had a CCI of 3. The total number of PE cases noted in the group without sickle cell trait was 181,565 while the number of PE cases in patient with sickle cell trait was 455 during the study period. We did a subgroup analysis in patients with sickle cell trait related hospitalization after adjusting for age, gender, race, CCI and the risk factors for PE such as smoking, oral contraceptive intake, obesity, history of thrombosis, thrombophilia, cancer, myeloproliferative neoplasms, fracture, COPD, and varicose veins using multivariate regression analysis. This revealed that the sickle cell trait group had higher odds of developing PE with an aOR – 1.56 (95% CI 1.26-1.94, p<0.001)

Conclusions: Our study shows that patients with sickle cell trait are at significantly increased odds of developing PE in comparison to patients without the trait. While this highlights the heightened thrombotic risk associated with sickle cell trait, we must also appreciate the fact that thus far the mechanism by which this happens is poorly understood. One proposed mechanism is tPA resistance induced by sickle cells indicating a complex interplay between various blood cell types. Further studies are needed to explore the role of sickle cell trait as a risk factor in adverse health outcomes.