Serum Biomarkers for Identifying Acute Chest Syndrome Among Patients Who Have Sickle Cell Disease and Present to the Emergency Department

Abstract

ABSTRACT. Objective. To compare the accuracy of biomarkers for identifying acute chest syndrome (ACS) in patients with sickle cell disease presenting to a pediatric emergency department (ED).Methods. We conducted a 13-month-long (2002-2003) cohort study with nested case-control in patients with sickle cell disease presenting to the pediatric ED with vaso-occlusive crises or fever in which we compared levels of secretory phospholipase A2 (sPLA2), endothelin-1, interleukin-6 (IL-6), and peripheral white blood cell count (WBC) in cases that were complicated by ACS and in control subjects with uncomplicated illnesses. For diagnosis, a test was considered to be accurate when the area under its receiver operator characteristic curve (AUC) was >0.70. Laboratory tests with AUC values >0.70 were entered into a binary recursive partitioning model for diagnosis.Results. For the period of study, samples from 72 visits were obtained from 51 patients who presented with vaso-occlusive crises (range: 1-4 visits per patient; 15 were enrolled more than once A cute chest syndrome (ACS), a combination of respiratory symptoms and radiographic evidence of new pulmonary infiltrates, is the second leading cause of hospitalization in patients with sickle cell disease (SCD). 1 The success of simple blood transfusions in the treatment of overt ACS is well established and raises the possibility of using such therapy earlier in the course of illness. 2-4 Symptoms of impending ACS, however, may be subtle, limiting the utility of the clinical examination. In fact, a recent study reported that half of ACS cases were diagnosed after patients had been admitted to the hospital with other complaints (most commonly, vaso-occlusive crises [VOC]). 2 A strategy of routine chest radiographs in patients who present with VOC may identify early cases of ACS but is undesirable because of the hazards associated with repeated exposure to radiation. Fortunately, other possibilities exist. A promising test is the level of secretory phospholipase A2 (sPLA2). In one small study, elevation of this enzyme predicted impending ACS in children with VOC. 5 No attempts have been made, however, to validate these findings at other sites. Another test is the endothelin-1 level in plasma, which has been shown to rise in VOC 6 but has not been evaluated for predicting ACS. Finally, peripheral blood leukocytes and interleukin (IL) levels increase in many inflammatory conditions and so may have value for detecting ACS. Among ILs, an attractive target for study is IL-6, a pleiotropic proinflammatory protein with many biologic activities that is reported to correlate positively with the number and adhesiveness of neutrophils in SCD. 7,8 For now, it is not clear how these biomarkers change in response to ACS. In this study, we addressed this question. Specifically, we validated the accuracy of sPLA2 in a new setting and compared its performance with that of other tests. For ACS detection, we also defined optimal test cutoffs and evaluated a strategy that combines these tests for...

Transfusion prevents acute chest syndrome predicted by elevated secretory phospholipase A2

“…In addition, it is presently not known how to treat a patient who is at risk for ACS. This pilot study has confirmed earlier studies (Styles et al , 2000; Naprawa et al , 2005) that sPLA 2 is an accurate predictor for ACS in those SCD patients hospitalised with VOE, as over 70% of patients eventually manifested ACS after their sPLA 2 rose to >100 ng/ml. Equally important, it was demonstrated that ACS could be prevented with the early use of packed red cell transfusions, using sPLA 2 as a screening tool.…”

Evidence for the endothelin system as an emerging therapeutic target for the treatment of chronic pain

“…Patient questionnaires using the visual analog scale revealed that pain severity decreased significantly in all patients during the treatment period 142. ET-1 was investigated as a potential marker for patients admitted to the emergency room for a sickle cell pain crisis and in patients with complex regional pain syndrome 143,144…”

Carotid and femoral intima-media thickness in adults with sickle cell disease

“…23 WBC count was found to be an accurate test for detecting acute chest syndrome in SCD patients who attended an emergency department (ED) with pain crises. 24 Castro O et al, noted that WBC count was associated with acute chest syndrome in patients with SCD. 25 Liem RI et al, reported SCD patients with acute chest syndrome had a higher WBC count compared to controls.…”