Sickle cell disease is complicated by veno-occlusive crises leading to pain crises, chronic end-organ damage and early mortality. With recent advances in the management of sickle cell disease in childhood, sickle cell patients are living longer. However, our understanding of the clinical course of adult sickle cell disease remains limited and is based largely on extrapolation of knowledge from children with sickle cell disease. Unfortunately, adult patients remain at an elevated risk of infections due to encapsulated organisms in the setting of functional asplenia. This risk is exacerbated by possible indwelling catheters and exposure to the health care environment. Fever in these patients can herald a serious infection. Alternatively, brisk hemolysis can be associated with fever. Wierenga, et. al. (2001) described that fevers to 39F in children were associated with acute chest syndrome (21%), painful vaso-occlusive crisis (27%), and bacteremia in 6%. To our knowledge, no such review of fever in hospitalized adult sickle cell patients has been published in the medical literature. Therefore, the clinician is placed in a diagnostic dilemma regarding the management of fever in adult patients with sickle cell disease.
To determine the etiologies of fevers in hospitalized adult patients with sickle cell disease in an urban tertiary hospital setting.
We performed an IRB-approved retrospective analysis of 143 admissions between 1995–2008 with sickle cell pain crisis and had a fever greater than 38.5C during the admission. The aim was to determine the prevalence of fevers due to infectious versus hemolysis-related causes in the population of interest. Elevated white blood cell count (defined as greater than 1.5x upper limit of normal), radiologic and/or culture data were used to classify a fever as due to infection. Elevated LDH and total bilirubin (defined as greater than 2x upper limit of normal) were used to classify a fever as due to hemolysis. The risks of infection in patients on hydroxyurea as well as indwelling catheters (including central lines and foley catheters) were assessed. We also evaluated the risk of hemolysis in patients on hydroxyurea. Finally, the use of antibiotics and duration of the fever in patients with hemolysis and infection were also evaluated.
Among patients admitted with sickle cell pain crisis and had a fever during their hospitalization, we found evidence of infection in 65% and hemolysis in 58%. Interestingly, 35% had evidence of both infection and hemolysis. Approximately, 11.8% had no significant evidence of infection or hemolysis. Antibiotics were used in 66% of all patients with pain crisis and fever. Among the patients who received antibiotics, 81% had evidence of infection and 19% had no evidence of infection. Approximately 1/5 patients with fevers received antibiotics despite the absence of evidence of infection. Infections were not increased among hydroxyurea users (61.5% with fever) over non-hydroxyurea users (67.9% with fever), p = 0.4. Fevers due to documented infections were found in 78% of patients with indwelling catheters compared with 62% of patients without catheters, p≤0.05. The risk of fever due to hemolysis was not significantly different between hydroxyurea and non-hydroxyurea users at 58% versus 57% respectively, p=0.9. Of patients with fevers for more than one day, infection was found in 69% of patients compared with 31% of patients who had no evidence of infection p=0.5. Whereas, of patients with fevers for more than one day, hemolysis was found in 57% of patients compared with 42% of patients who did not have evidence of hemolysis with p=0.9.
Among adult sickle cell patients hospitalized with pain crisis and fever, hemolysis accounted for 58% of cases while infections accounted for 65% with 35% evidence of both. Infections were not increased among hydroxyurea users. Indwelling catheters did increase the risk of fevers due to infection. The risk of fever due to hemolysis was not significantly increased among patients on hydroxyurea. Finally, in patients with fevers for more than one day, hemolysis accounted for 57% of cases and infection accounted for 45%. These findings provide initial investigation of the etiologies of fevers in adult hospitalized sickle cell patients and further studies are necessary to confirm these findings. Disclosures: No relevant conflicts of interest to declare.
No relevant conflicts of interest to declare.
Asterisk with author names denotes non-ASH members.