Clinical and laboratory findings in adults with sickle cell disease which increase risk for severe acute chest syndrome

Abstract

Abstract Introduction Acute chest syndrome (ACS), the second most common complication of sickle cell disease (SCD), is characterized by a new lung infiltrate on chest radiography, plus fever and/or respiratory symptoms. ACS often develops on days 1-3 of hospitalization for acute vasoocclusive pain crises and is a major cause of morbidity and mortality. It is difficult to determine which patients with SCD will develop ACS, and of those with ACS, who will have a more severe disease course. The SCD outcomes grading system (SCOGS) was developed following a three round Delphi consensus methodology that included contributions from 29 clinical SCD experts, in addition to 18 organ-specific experts from across North America. This system standardizes the classification and grading of the severity of 53 different complications of SCD. ACS severity is graded 1-5 depending on if the patient: 1) Received antibiotics without any other supportive measures; 2) Required simple transfusion and/or ≤50% fractional inspired oxygen (FiO2); 3) Required >50% FiO2, use of non-invasive ventilation, high flow O2 and/or exchange transfusion, 4) Required mechanical ventilation, vasopressors and/or organ support; and 5) Died as a consequence of ACS. Our study aimed to determine the risk factors predictive of severe ACS (Grade 4 or 5) using the SCOGS severity scale. Methods Adult patients with SCD who were hospitalized at a single institution between January 1, 2021 and December 31, 2022 were identified from the electronic medical record. Patients were identified from a clinical data warehouse based on ICD-10 billing codes with case confirmation by chart review. ACS was defined as those with a new lung infiltrate on chest radiography, plus fever and/or respiratory symptoms. Data collected included demographics, past medical history, vital signs, laboratories and treatment. Using the SCOGS scale, ACS cases were grouped by severity into mild (SCOGS Grade 1–2), moderate (SCOGS Grade 3), and severe (SCOGS Grade 4–5). Descriptive statistics (mean, SD) were calculated. One-way ANOVA was performed to compare continuous variables across ACS severity groups. Data were analyzed using SAS 9.4. Statistical significance was defined as a p-value < 0.05. Results Of the 112 hospitalizations reviewed, 109 met criteria for ACS and were included in the final analysis. 100% of the 109 reviewed ACS cases had the appropriate data to be graded with the SCOGS scale. 51.8% of patients were male, 89.3% were Black, and 83.9% had HbSS disease. The median age was 33.5 years (SD +/- 10.2 years). 86.6% had prior ACS episodes, 17.9% had prior stroke, and 38.4% had prior venous thromboembolism. 92 cases were consistent with mild ACS, 10 were moderate, and 7 were severe. There were 4 deaths, one of which resulted from non-small cell lung cancer (non-ACS related). The severe ACS group had the lowest oxygen saturation on presentation (92.3%) which differed significantly from the mild (96.0%) and moderate (96.1%) groups (p=0.03). The severe ACS group had the lowest hemoglobin concentration (p=0.02), and highest total bilirubin (p=0.04), and highest creatinine (p=0.002) levels compared with those with mild or moderate ACS. Compared to mild and severe ACS, the moderate ACS group had a higher white blood cell count (p=0.02). There was no significant difference in the reticulocyte count or platelet count amongst patients with differing ACS severity. Conclusion Adult patients with SCD and ACS present with a spectrum of disease severities. Severe ACS, identified by the SCOGS severity scale, is characterized by worsening anemia and multi-organ dysfunction. While our findings need to be confirmed prospectively in a larger cohort, our data suggest that initial presenting vital signs and laboratories can identify patients at increased risk for mortality, warranting advanced therapies, including exchange transfusion and/or intensive care unit support.