Abstract

Acute chest syndrome (ACS) is a frequent cause of morbidity and the leading cause of death among individuals with sickle cell disease. Prior studies of ACS in hemoglobin SC disease, however, have been limited in scope and the risk factors and clinical outcomes associated with ACS in individuals with hemoglobin SC versus SS disease remain unclear. The objective of this study was to compare the presentation and clinical course of ACS in individuals with SC disease to that observed in individuals with SS disease. We hypothesized that in SC disease, ACS is associated with a more severe clinical course compared to that observed in SS disease. Using available hospital medical records, we performed a retrospective analysis of all episodes of ACS diagnosed either on admission or during hospitalization in patients with SC disease over a 20-year period from 1987 through 2007. Control cases meeting identical criteria in patients with hemoglobin SS disease were randomly sampled within a 5-year period of the occurrence of each SC episode. We performed standard descriptive analysis and compared both continuous (Mann-Whitney test) and categorical data (Pearson’s χ2 analysis) in SC and SS episodes of ACS. Standard regression analysis was performed to evaluate predictors of length of hospitalization, our primary outcome for clinical severity. A total of 71 episodes of ACS in 30 SC patients and 137 episodes in 92 SS patients were reviewed. We found that in episodes involving SC patients, median age (7.0 vs. 5.0 years, p=0.014), baseline hemoglobin (10.5 vs. 8.1 g/dL, p=0.001) and oxygen saturation on presentation (97 vs. 94%, p=0.001) were significantly higher when compared to that in episodes involving SS patients. In SC cases, a history of asthma or wheezing (50.7 vs. 34.3%, p=0.022, OR=1.98) was significantly more common than in SS cases. In addition, complaints of chest pain (40.8 vs. 22.8%, p=0.007, OR=2.34) and wheezing (11.3 vs. 3.7%, p=0.033, OR=3.34) on presentation were significantly more frequent in the SC group. At the time of diagnosis of ACS in SC patients, median total white blood cells (15.3 vs. 19.6 x103 cells/uL, p=0.001), platelets (206 vs. 343 x103/uL, p=0.001), nucleated red blood cells (0 vs. 2.0 per 100 WBC, p=0.001), reticulocytes (3.0 vs. 12.7%, p=0.001) and percent lymphocytes (15.0 vs. 22.5%, p=0.002) were lower, but hemoglobin (9.3 vs. 7.4 g/dL, p=0.001) and total percent neutrophils and bands (74.5 vs. 65.0%, p=0.001) were higher than at diagnosis in the SS group. Other significant findings included less hypoxia on admission (9.2 vs. 29.3%, p=0.002, OR=0.25) as well as less oxygen use (45.1 vs. 64.2%, p=0.008, OR=0.46) and less transfusion support (31.0 vs. 72.3%, p=0.001, OR=0.17) documented during hospitalization in the SC group. Despite the more frequent history of asthma and complaint of wheezing on presentation in the SC group, neither the use of asthma medications nor the duration of oxygen support in those patients who required it differed during episodes of ACS in SC versus SS patients. The frequency of vaso-occlusive pain on admission, transfusion support during hospitalization and time to transfusion also did not differ between the 2 groups. No deaths were recorded in any hemoglobin SC patients, while 1 death occurred in the SS group. There was no significant difference in median length of hospitalization in ACS episodes involving SC versus SS patients (3.0 vs. 4.0 days, p=0.107). A model that included age, baseline hemoglobin, time to transfusion and total days of oxygen support accounted for 75% and 60% of the variation in length of hospitalization in the SC and SS groups, respectively. Age, time to transfusion and duration of oxygen support represented independent contributors in both groups. In conclusion, our data suggest for the first time that asthma and wheezing may represent significant risk factors for ACS more commonly in SC patients when compared to SS patients. Clinical severity, as determined by length of hospitalization, was similar in episodes of ACS involving patients with hemoglobin SC and SS disease. Other markers of clinical severity associated with ACS, such as transfusion and oxygen requirements, appear related to baseline differences in laboratory and clinical presentation between individuals with SC and SS disease. Future studies to definitively evaluate in SC patients the relationship between asthma and ACS, as well as its impact on management of ACS, are warranted.

Disclosures: No relevant conflicts of interest to declare.

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