Sickle Cell Disease: Acute Chest Syndrome

5/05/00 (Del Rio)

Group: Friday Interns

RE: A 19 year old male with sickle cell disease and suspected pneumonia.

Question: What are aspects of the acute chest syndrome in sickle cell anemia?

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Accession Number: 10801164

Authors: Gladwin, MT; Rodgers, GP

Institution: Department of Critical Care Medicine, NIDDK National Institutes of Health, Bethesda, Maryland, USA.

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Unique Identifier: 99409027

Authors: Stuart MJ. Setty BN.

Institution: Department of Pediatrics and the Cardeza Foundation for Hematologic Research, Thomas Jefferson University,: Philadelphia, PA 19107, USA.

Abstract: Acute chest syndrome (ACS) is a leading cause of death in sickle cell disease (SCD). Our previous work showed that: hypoxia enhances the ability of sickle erythrocytes to adhere to human microvessel endothelium via interaction between: very late activation antigen-4 (VLA4) expressed on sickle erythrocytes and the endothelial adhesion molecule vascular: cell adhesion molecule-1 (VCAM-1). Additionally, hypoxia has been shown to decrease the production of nitric oxide: (NO) which inhibits VCAM-1 upregulation. Based on these observations, we hypothesize that during ACS, the rapidly: progressive clinical course that can occur is caused by initial hypoxia-induced pulmonary endothelial VCAM-1: upregulation that is not counterbalanced by production of cytoprotective mediators, including NO, resulting in: intrapulmonary adhesion. We assessed plasma NO metabolites and soluble VCAM-1 in 36 patients with SCD and 23: age-matched controls. Patients with SCD were evaluated at baseline (n = 36), in vaso-occlusive crisis (VOC; n = 12),: and during ACS (n = 7). We observed marked upregulation of VCAM-1 during ACS (1,290 +/- 451 ng per mL; mean: +/- 1 SD) with values significantly higher than controls (P <.0001) or patients either in steady state or VOC (P <. 01).: NO metabolites were concomitantly decreased during ACS (9.2 +/- 1.5 nmol/mL) with values lower than controls (22.2: +/- 5.5), patients during steady state (21.4 +/- 5.5), or VOC (14.2 +/- 1.2) (P <.0001). Additionally, the ratio of: soluble VCAM-1 to NO metabolites during ACS (132.9 +/- 46.5) was significantly higher when compared with: controls (P <.0001) or patients either in steady state or VOC (P <.0001). Although hypoxia enhanced in vitro sickle: erythrocyte-pulmonary microvessel adhesion, NO donors inhibited this process with concomitant inhibition of VCAM-1.: We suggest that in ACS there is pathologic over expression of endothelial VCAM-1. Our investigations also provide a: rationale for the therapeutic use in ACS of cytoprotective modulators including NO and dexamethasone, which: potentially exert their efficacy by an inhibitory effect on VCAM-1 and concomitant inhibition of sickle: erythrocyte-endothelial adhesion.

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Link Directly to Fulltext article in Ovid

Unique Identifier: 99315127

Authors: Morris C. Vichinsky E. Styles L.

Institution: Departments of Emergency Medicine and Hematology/Oncology, Children's Hospital Oakland, Oakland, CA, USA.: lstyles@lanminds.com

Abstract: STUDY OBJECTIVE: To determine whether the use of empiric chest radiography (CXR) is of significant value in: detecting clinically unsuspected acute chest syndrome (ACS) in febrile patients with sickle cell disease (SCD).: METHODS: Patients with SCD presenting to the emergency department and hematology clinic with temperature: greater than or equal to 38 degrees C were prospectively evaluated using a physician-completed questionnaire. The: questionnaire included inquiries into the patient's physical signs and symptoms and the physician's clinical impression for: the presence of ACS. The questionnaire was completed before obtaining CXR results in all patients. RESULTS:: Seventy-three patients with SCD with 96 febrile events were evaluated over a 1-year period. Twenty-four percent: (23/96) of the patients had CXR evidence of ACS. On the basis of the questionnaire data, 61% (14/23) of ACS cases: were not clinically suspected by the evaluating physician before obtaining CXR. Comparing the patients with and without: ACS revealed that, with the exception of splinting (4/23 [17%] versus 0/73 [0%]), no symptom or physical examination: finding helped to identify which patients had ACS. Fifty-seven percent of patients with ACS had completely normal: findings on physical examination. The presentation of patients with clinically detected versus clinically unsuspected ACS: also did not differ significantly. Length of hospitalization, oxygen use, and need for transfusion were the same in both the: unsuspected and detected ACS groups. Overall physician sensitivity for predicting ACS was only 39%, and diagnostic: accuracy did not improve significantly with increasing levels of pediatric training. CONCLUSION: ACS is common in: patients with SCD who present with fever and was grossly underestimated by evaluating physicians. History and physical: examination appear to be of little value in defining which febrile patients require CXR. In view of the mortality and: morbidity associated with ACS, empiric CXR should be considered when evaluating a febrile patient with SCD.