Procalcitonin Levels Predict Bacterial Infections and Clinical Outcomes in Adults with Sickle Cell Disease

Introduction: Adults with sickle cell disease (SCD) experience frequent hospitalizations for vaso-occlusive episodes (VOE) and acute chest syndrome (ACS), with over 230,000 hospitalizations in the United States each year alone (PMID 32301178). Many VOE and ACS episodes are complicated by fevers and leukocytosis and a tool to identify bacterial infections to guide antibiotic therapy would be clinically useful. Procalcitonin has been identified as a marker to identify hospitalized patients at risk for bacterial infection and to guide antibiotic therapy (PMID 26947532; PMID 19738090). The objective of this study was to evaluate whether procalcitonin can identify SCD patients at greater risk for developing a bacterial infection and predict clinical outcomes in those hospitalized for a VOE or ACS episode.

Methods: We retrospectively identified 114 adults with SCD who were hospitalized between March 2018 and December 2022 at an urban academic hospital who had a procalcitonin level drawn during their admission for a VOE or ACS episode. For patients with multiple admissions, only the first admission with a procalcitonin level was used in this analysis. Vital signs at the time of admission, laboratory results from the same day the procalcitonin level was drawn, and subsequent infection work up and clinical outcomes were collected from the electronic medical records. Procalcitonin thresholds that were tested were determined a priori based upon our laboratory reference values and from the literature as > 0.1ng/mL, > 0.25ng/mL, or > 0.5nl/mL. Univariate analyses of variables by procalcitonin level were performed by Kruskal-Wallis or Chi-square test. Linear and logistic regression analyses were used to test the independent associations of an elevated procalcitonin with clinical outcomes. Median values are provided.

Results: The median age of the cohort was 40 years (interquartile range, 30 - 51 years), 68% were female, 80% had hemoglobin SS genotype, and 52% were on hydroxyurea therapy. A procalcitonin level of ≥ 0.5 ng/mL, observed in 34 (30%) patients was associated with a documented bacterial infection (OR 2.61, 95% CI: 1.14 - 6.01; P = 0.02), which we defined as a positive blood (n = 10) or urine culture (n = 16) or a new lung consolidation with a negative respiratory viral panel by PCR (n = 39). Procalcitonin thresholds of ≥ 0.1 or ≥ 0.25ng/mL were not predictive of a documented bacterial infection (P≥0.3). SCD patients with a procalcitonin level of ≥ 0.5 ng/mL had a trend for a higher white blood cell count (14.2 vs. 13.4 x 10⁹ cells/L; P=0.053). A procalcitonin level of ≥ 0.5 ng/mL remained a significant predictor of a documented bacterial infection (OR 2.36, 95% CI: 1.02 - 5.60; P = 0.045) after adjusting for the white blood cell count (P=0.4).

Next, we evaluated the associations of a procalcitonin ≥ 0.5 ng/mL with health-related outcomes. Those with an elevated procalcitonin had a greater number of days requiring antibiotics (7 vs. 3 days; P < 0.0001) and a longer number of inpatient hospital days (9 vs. 6 days; P = 0.0099). Those with an elevated procalcitonin were more likely to be diagnosed with ACS (49% vs. 20%; P=0.0015) and require care in the medical intensive care unit (MICU) (32% vs. 11%; P = 0.0067). An elevated procalcitonin ≥ 0.5 ng/mL was independently associated with length of hospitalization (β 2.88 ± 1.46; P=0.05), ACS (OR 3.82; 95% CI: 1.58-9.22; P=0.0029) and MICU admission (OR 4.88, 95% CI: 1.65-14.40; P = 0.0042) after adjusting for age, sex, SCD genotype, and hydroxyurea use.

Conclusions: Our findings suggest that a procalcitonin level ≥ 0.5 ng/mL is a biomarker that predicts a 2-fold greater risk of a bacterial infection in hospitalized patients with SCD. Furthermore, patients with SCD who have a procalcitonin level above this threshold are more likely to have ACS, a longer hospitalization, and require care in the MICU. Future investigation of procalcitonin as a biomarker to identify those at risk for bacterial infections and ACS may help guide clinicians target the use of antibiotic therapy and intervene earlier in order to mitigate the high morbidity and mortality of ACS episodes in SCD.