Background:

Acute chest syndrome (ACS) is a well-known complication in sickle cell disease with significant mortality and worse outcomes (Allareddy et al. 2014), but its occurrence in patients with preexisting Pulmonary Embolism (PE) is not well explored (Klings et al. 2025). The impact of first-time ACS on inpatient outcomes in this population remains nebulous, with implications extending beyond awareness to include anticoagulant dosage and duration (Dessap et al. 2025)

Methods:

A retrospective cohort analysis using the United States National Inpatient Sample (NIS), which were developed for the Healthcare Cost and Utilization Project (HCUP) Database from 2016-2022 was conducted. Patients admitted with a primary diagnosis of a first episode of Acute Chest Syndrome (ACS), with preexisting Pulmonary Embolism (PE) were identified using ICD-10 codes. The primary outcome was in-hospital mortality. Secondary outcomes were length of stay, resource utilization and need of various interventions. Univariate analysis was done and variables with p<0.2 were considered for multivariate analysis, adjusting by age, gender, race, Charlson comorbidity index, hospital location and teaching status, size, region and insurance status. Data was considered statistically significant with p-value <0.05.

Results: Between 2016-2022, there were 36,449 patients that were admitted for first-time ACS from 2016-2022. Less than 3% of them (n= 895, 2.45%) had preexisting PE. Patients were primarily female (53.6%), Black (91.4%), with a 0 or 1 score on the Charleston Comorbidity Index (CCI) (50.2% and 33.0% respectively) and had a mean age of 31.9 years old. These patients most often had either Medicare (26.0%), Medicaid (45.2%), or private insurance (24.9%), and earned in the lower two quartiles of median household income (73.6%). Most of the patients with preexisting PE presented with first-time ACS to large (65.9%) and urban teaching hospitals (87.1%). Interestingly, while most of the patients with first-time ACS were diagnosed in the South (48.9%), there was statistically significant difference (p=0.0232) in patients with and without preexisting PE by region, notably in the Midwest (18.6% without PE vs. 27.4% with) and the South (49.1% without PE, 41.3% with).

Patients with preexisting PE and first-time ACS had over a 6-times (OR=6.95, 95% CI 3.31 - 14.60, p < 0.001) increase in the odds of mortality; a multivariate analysis showed increased odds of mortality with older age (OR=1.04, 95% CI 1.02 - 1.07, p<0.001) and increased odds of mortality with higher Charleston Comorbidity Index (CCI 2: OR=4.63, 95% CI 2.34 - 9.17 p<0.001, CCI 3: 3.12, CI 1.46 - 6.66 p<0.001). There was an average increase in the mean length of stay by 3.43 days (CI 1.63 - 5.23, p = 0.012) with an average increase in the mean total charges for hospital stay by $47,236 (95% CI 22,324 – 72,147, p < 0.001). While there was no significant difference in the rates of red blood cell transfusion, these individuals had over a 2-times increase in the odds of undergoing Intubation (OR=2.24, 95% CI 1.10 - 4.58, p < 0.001) and the increased rates of hemodialysis requirements which trended towards significant (OR=5.02, 95% CI 0.78 - 32.35, p=0.09).

Conclusion: In conclusion, the connection between first-time ACS in patients who have previously experienced a pulmonary embolism is clear. In our study we show that not only is there an increase in mortality, but worse in-hospital outcomes including length of stay, total charges, and intubation. Furthermore, our multivariate analysis shows that specific populations, including those with increased comorbidities need special attention due to worse outcomes. It is possible that a hypercoagulable state, which is a consequence of sickle cell disease, is behind both etiologies. While previous research has touched on the connection and subsequent impact, it is evident that more research and awareness is needed regarding preexisting PE and first-time ACS to guide management.

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2025
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