C-Reactive Protein As a Predictor Of Bacterial Disease In Children With Sickle Cell Disease and Fever

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4682-4682
Author(s):  
Maria Olivares ◽  
Matthew W Richardson ◽  
Paul Visintainer

Introduction Children with sickle cell disease (SCD) are at increased risk of serious bacterial disease compared to children without SCD. Children with SCD and fever are recommended to undergo prompt evaluation, including a physical exam, complete blood count, blood culture, and sometimes chest x-ray. These children often receive empiric parenteral antibiotics until blood cultures show no bacteremia for forty-eight hours. Studies in this population have identified clinical and laboratory features that are associated with low rates of bacteremia or that predict bacteremia. C-reactive protein is an acute phase reactant that has been studied as a predictor for bacteremia in a variety of clinical situations. Crp, however, has not been evaluated as a predictor of serious bacterial disease in children with SCD. Method Retrospective chart review of children age 0 – 18.9 year old admitted to Baystate Children’s Hospital with a diagnosis of SCD and fever who had crp and blood culture drawn between January 1, 2009 and December 31, 2011. SCD included homozygous SS disease, SC disease, or Sβ-thalassemia. Bacterial disease was defined as bacteremia, osteomyelitis, pneumonia/ acute chest syndrome, pyelonephritis. Parental report of fever was accepted. Age, maximum temperature, white blood count (WBC), absolute neutrophil count (ANC), percent of neutrophils (ANC/WBC), and crp were evaluated. Results 80 cases met inclusion criteria. 18 cases had bacterial disease. Compared to children without bacterial disease, those with bacterial disease were older (mean age 11 vs. 4.8 yr, p < 0.001), had higher mean crp (5.7 vs. 1.6 mg/dL, p <0.001), higher mean WBC (20.9 vs. 15.6 x 103/mm3, p = 0.004), and higher mean ANC (13.5 vs. 8.7 x 103/mm3, p = 0.002). There were no significant differences between maximum temperature and percent neutrophils between the two groups. After regression analysis for all variables, age and crp remained significant between the two groups (p = 0.001 for both). A receiver operator characteristic (ROC) curve using crp and age produced an area under the curve of 0.87. Conclusions Children with SCD hospitalized for fever and diagnosed with bacterial illnesses are older and have higher crp compared to those without bacterial illness. The ROC curve based age and crp has characteristics of a good screening test. Because children with SCD and fever will usually receive empiric antibiotics regardless and the repercussions of a missed bacterial illness are great, using crp to determine antibiotic administration is likely limited. Rather, a low crp, especially in a younger child, may be helpful to determine patients who are candidates for early discharge or those who can be managed as an outpatient. Prospective use of crp for fever in this population, including outpatients, is warranted in order to identify the best sensitivity and specificity. Disclosures: No relevant conflicts of interest to declare.

Blood ◽  
2005 ◽  
Vol 105 (8) ◽  
pp. 3384-3385 ◽  
Author(s):  
Emilee M. Bargoma ◽  
Joyce K. Mitsuyoshi ◽  
Sandra K. Larkin ◽  
Lori A. Styles ◽  
Frans A. Kuypers ◽  
...  

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2485-2485
Author(s):  
Iheanyi Okpala ◽  
Ndubuisi Uwaezuoke ◽  
Ifeoma Emodi ◽  
Anthony Ikefuna ◽  
Tagbo Oguonu

Abstract Introduction The severity of sickle cell disease (SCD) increases with absolute neutrophil count (ANC, Eur J Haematol. 1998; 60: 267-8) and expression of adhesion molecules by leukocytes (Eur J Haematol. 2002; 69: 135 -144.). Intercellular adhesion molecule 1 (ICAM 1) on vascular endothelium mediates leukocyte adherence to the blood vessel wall. This contributes to vaso-occlusion, the main mechanism of tissue damage in SCD. Micro-RNA 221 (MIR 221) regulates the gene for ICAM-1 (J Cell Science 2011; 124, 999-1006). How the severity of SCD relates with expression of MIR 221 was evaluated in this study. Methods Following IRB approval and informed consent by appropriate persons, 25 healthy HbAA control persons and 73 HbSS patients (45M, 28F; age 2-18 yrs) were consecutively enrolled from University of Nigeria Teaching Hospital, Enugu. Patients who had blood transfusion in the previous 3 months were excluded. Information from medical records and clinical assessment was used to determine the SCD Severity Score according to the system previously validated by Cameron et al (J Nat Med Assoc. 1983; 75: 483-7). This system assigns scores to age at which the first symptom of SCD occurred, number of hospital admissions due to SCD per year, number of painful episodes per year, type of sickle cell crisis, number of major organ complications of SCD, pneumococcal sepsis, and the degree of failure to thrive assessed with patient's height and weight percentiles. A total score up to 4 indicates mild, 5-8 moderate, and 9-21 severe SCD. Absolute neutrophil count (ANC) and Hb level were determined with an automated blood analyser, plasma level of soluble ICAM-1 (sICAM-1) by enzyme-linked immunosorbent assay (ELISA), and expression of MIR 221 in leukocytes by polymerase chain reaction with fluorescent probes to enable quantification. To obtain a composite picture of the relationship between study parameters, 4mls of venous blood from each patient was analysed during vaso-occlusive crisis; and 4 weeks after the crisis had resolved (steady state). To help evaluate the degree of resolution of the crisis and the level of inflammation in each patient, the concentration of C-reactive protein was measured by ELISA in blood samples taken during crisis and steady state. The GraphPad Prism statistical package version 5.03 was used for data analyses. Following D'Agostino and Pearson's Omnibus normality test which showed that the values of MIR 221expression, sICAM 1 concentration, and ANC did not have a normal (Gaussian) distribution, median values and non-parametric tests were used for statistical analyses of these data. Results Based on Cameron Severity Scores, 25 patients had mild, 36 moderate and 12 severe SCD. The mean severity score for all patients was 5.85± 2.31. Median leukocyte MIR-221 of 3,092 copies/5ul of cDNA in steady state was comparable to 3,764 copies/5ul of cDNA in crisis (p = 0.6, Table 1). Both values were significantly higher than the median leukocyte MIR221 of 1428 copies/5ul of cDNA in healthy HbAA controls; P<0.0001. The quantity of MIR221 in leukocytes in mild SCD (median 3092 copies/5ul of cDNA) was significantly different from that in moderate disease (median 4004 copies/5ul of CDNA) which, in turn, differed significantly from that in severe SCD (median 5587 copies/5ul of cDNA, p< 0.05, Kruskal-Wallis Test). Spearman's correlation coefficient (Rho) between the Cameron Severity Scores in patients with severe SCD and the quantity of MIR 221 in leukocytes during steady state was high at 0.72 (Table 2). The quantity of MIR 221 in leukocytes during steady state emerged as a stronger correlate of SCD severity than ANC (Table 3). As crisis resolved and steady state returned, the inflammatory markers C-reactive protein (Kruskal-Wallis test, p=0.0003) and ANC (Wilcoxon matched pairs test; p<0.0001) reduced. Conclusions The strong correlation between severity of SCD and the quantity of leukocyte MIR 221 in steady state suggests that leukocyte MIR 221 is a candidate biomarker for assessing the severity of SCD. The quantity of MIR 221 in leukocytes, unlike ANC, did not change significantly from crisis to steady state in this study; and could be a more consistent and stronger index of SCD severity than absolute neutrophil count. As a regulator of the gene for ICAM 1 which contributes to leukocyte adhesion and organ damage, the role of MIR 221 in SCD deserves further studies in view of the potential benefit of anti-adhesion therapy. Disclosures No relevant conflicts of interest to declare.


2015 ◽  
Vol 9 (1) ◽  
pp. 26-29
Author(s):  
Jeffrey Gershel ◽  
Robyn Kreiner ◽  
Gila Spitzer ◽  
Adam Sterman ◽  
Emily Slotkin ◽  
...  

2010 ◽  
Vol 45 (4) ◽  
pp. 293-296 ◽  
Author(s):  
Fatima A. Mohammed ◽  
Najat Mahdi ◽  
Mai A. Sater ◽  
Khadija Al-Ola ◽  
Wassim Y. Almawi

2012 ◽  
Vol 34 (2) ◽  
pp. 85-89 ◽  
Author(s):  
Selma Unal ◽  
Ali Ertug Arslankoylu ◽  
Necdet Kuyucu ◽  
Gönül Aslan ◽  
Semra Erdogan

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3214-3214
Author(s):  
Ami P Patel ◽  
Amra Zuzo ◽  
Hamayun Imran ◽  
Abdul H Siddiqui

Abstract Abstract 3214 Introduction: Children with sickle cell disease are at a high risk of death from pneumococcal bacteremia due to functional asplenia. The common practice for management of any fever in a child with sickle cell disease is in-patient antibiotic therapy for presumed bacteremia, until the blood cultures have remained negative for 48 hours. We hypothesize that interventions such as penicillin prophylaxis, use of polyvalent pneumococcal vaccine at 2 years of age in addition to the primary immunization series with pneumococcal conjugate vaccine 13 have decreased the prevalence of pneumococcal bacteremia in children with sickle cell disease. Outpatient management of an uncomplicated febrile illness may be a safe alternative. Methods: We conducted a retrospective chart review of children with sickle cell disease hospitalized with a fever at Children's and Women's Hospital between January 2006 and June 2012. We collected demographical parameters, temperature, white blood cell count and C-reactive protein level at the time of presentation as possible predictors of true bacteremia. The continuous variables were compared between the two groups (positive and negative blood cultures) using independent t-test. We also recorded the time to positivity of blood cultures, pathogens identified in positive blood cultures, serotypes and sensitivities of pneumococcal bacteria. Results: A total of 133 patients, aged 2 months to 18 years, met the inclusion criteria with 456 hospital admissions. The prevalence of culture proven bacteremia was 3.7% with only two (0.44%) cases of pneumococcal bacteremia. We have not had any patient with pneumococcal bacteremia reported since the start of pneumococcal conjugate vaccine 13, in May 2010. Both the patients with pneumococcal bacteremia were older than five years and had discontinued taking penicillin prophylaxis. The first patient was fully vaccinated with pneumococcal conjugate vaccine 7 but had not received polyvalent vaccine. She contracted a non-vaccine serotype (23B) that was susceptible to penicillin, ceftriaxone, and vancomycin. The second patient was partially vaccinated and acquired a serotype (23F) that is included in pneumococcal conjugate vaccine 7. The bacterium was resistant to penicillin but sensitive to ceftriaxone and vancomycin. In the analysis of predictors of bacteremia, the average C-reactive protein level was found to be 6.3mg/dL in patients with positive blood cultures and 4.5mg/dL in patients with negative blood cultures (p=0.02). The mean age of patients with positive blood cultures was 11 years compared to 7.4 years in patients with negative blood cultures (p=0.03). The differences in body temperature and white blood cell count between the two groups were not statistically significant. The average time to positivity measured from the time of collection was 25.4 hours. Discussion: Penicillin prophylaxis and complete immunization, in accordance with the centers for disease control and prevention guidelines are important for patients with sickle cell disease. Patients with an uncomplicated febrile illness may not necessarily need to be hospitalized to continue antibiotics. We support an outpatient care model proposed by Williams et al, comprising of a single 24-hour dose of ceftriaxone followed by oral cefixime for 5 days and follow-up telephone calls by a nurse. Good patient education may help ensure compliance with outpatient care. Outpatient management of an uncomplicated febrile illness will be more cost-effective and beneficial to the patients and families. With this approach, however, patients may not be fully protected against ceftriaxone resistant pneumococccal infections. Bacterial resistance patterns in the community should be brought under consideration when implementing such a model. Conclusion: The prevalence of pneumococcal bacteremia in children with sickle cell disease has decreased in the past few years. In our analyses, we found older age and an elevated C-reactive protein level to be statistically significant predictors of a positive blood culture. Disclosures: No relevant conflicts of interest to declare.


Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1741-1741
Author(s):  
Katherine Eisenbrown ◽  
Oluwakemi Badaki ◽  
Angela M. Ellison ◽  
Mark Nimmer ◽  
David C. Brousseau

Abstract Background The National Heart, Lung, and Blood Institute Consensus Expert Panel recommends emergency department evaluation for all patients with sickle cell disease who develop a fever. However, it is unclear what recommended components are present in institutional care plans for their patients with sickle cell disease and what variation exists in the evaluation of patients who present with sickle cell disease and fever across institutions. There are few studies evaluating this practice variation and little evidence concerning the appropriate work-up of these children. Our objective was to describe areas where significant practice variation exists in the care of children with sickle cell disease presenting with fever to established sickle cell centers. Methods We undertook a retrospective cross-sectional study of the actual care received at three comprehensive sickle cell centers at pediatric hospitals to understand the diagnostic evaluation, treatment and disposition of children ages 3 months to 21 years presenting to the emergency department with sickle cell disease and fever. Chart reviews were performed on all visits of children presenting with a diagnosis of sickle cell disease to the emergency department of one of the three participating sites between January 1, 2008 and December 31, 2012. All charts were reviewed, and any chart with a documented fever ≥ 38.5°C, either at home or in the emergency department, was included for analysis. Data abstraction included laboratory and radiographic evaluation as well as antibiotic use and disposition. All children pretreated with an antibiotic within the past 24 hours were excluded from the analysis as this could alter the diagnostic evaluation and disposition of these patients. Descriptive statistics were used to determine the percent of children who received a chest radiograph, blood culture, complete blood count, urinalysis, electrolytes, treatment with an antibiotic, and disposition of hospital admission. Due to the large sample sizes, relatively small differences in proportions were determined to be statistically significant; however, differences of less than 10 percent were not considered to necessarily be indicative of clinically meaningful differences in evaluation or treatment, and therefore differences smaller than 10% were reported as similar. Results Analysis to date reveals complete evaluation of 1251 visits [673 at the Children's Hospital of Wisconsin (CHW), 368 at Children's National Medical Center (CNMC), and 210 at Children's Hospital of Philadelphia (CHOP)]. The median age of the children at these visits was 3.4 years (interquartile range of 1.4 - 7.7). Analysis of diagnostic testing revealed approximately 98 percent of patients received a complete blood count and a blood culture, with no difference between sites. Ninety-three percent of patients were treated with an antibiotic, which also showed no meaningful difference across sites. Analysis of disposition revealed significant differences between sites, with 49%, 47%, and 100% of patients admitted to the inpatient units at CHW, CNMC and CHOP, respectively. Likewise, significant differences were seen in obtaining chest radiographs: 81%, 92%, and 29% at CHW, CNMC and CHOP, respectively. The percent of patients who received a urinalysis ranged from a high of 39% at CNMC to a low of 18% at CHOP. Electrolytes were obtained from 3%, 48% and 1% of patients at CHW, CNMC and CHOP, respectively. Conclusion Consistent with NHLBI guidelines, essentially all children with sickle cell disease presenting to the emergency department with fever receive a complete blood count, blood culture and antibiotics. These equal proportions suggest similar treatment guidelines across sites. There is significant variation between sites in the proportion of children who receive a chest x-ray, urinalysis, electrolytes and perhaps most importantly, admission to the hospital. These examples of practice variation may represent potential areas for quality improvement efforts to better define best care practices for children with sickle cell disease presenting to the emergency department for fever. Disclosures: No relevant conflicts of interest to declare.


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