title: Refining the value of secretory phospholipase A2 as a predictor of acute chest syndrome in sickle cell disease: results of a feasibility study (PROACTIVE).
abstract: Acute chest syndrome (ACS) is defined as fever, respiratory symptoms and a new pulmonary infiltrate in an individual with sickle cell disease (SCD). Nearly half of ACS episodes occur in SCD patients already hospitalized, potentially permitting pre-emptive therapy in high-risk patients. Simple transfusion of red blood cells may abort ACS if given to patients hospitalized for pain who develop fever and elevated levels of secretory phospholipase A2 (sPLA2). In a feasibility study (PROACTIVE; ClinicalTrials.gov NCT00951808), patients hospitalized for pain who developed fever and elevated sPLA2 were eligible for randomization to transfusion or observation; all others were enrolled in an observational arm. Of 237 enrolled, only 10 were randomized; one of the four to receive transfusion had delayed treatment. Of 233 subjects receiving standard care, 22 developed ACS. A threshold level of sPLA2 ≥ 48 ng/ml gave optimal sensitivity (73%), specificity (71%) and accuracy (71%), but a positive predictive value of only 24%. The predictive value of sPLA2 was improved in adults and patients with chest or back pain, lower haemoglobin concentration and higher white blood cell counts, and in those receiving less than two-thirds maintenance fluids. The hurdles identified in PROACTIVE should facilitate design of a larger, definitive, phase 3 randomized controlled trial.
authors.affiliation: Pediatric Sickle Cell Program, Children's Hospital & Research Center Oakland, CA, USA. lstyles@mail.cho.org
authors.forename: Lori
authors.initials: L
authors.lastname: Styles
authors.forename: Carrie G
authors.initials: CG
authors.lastname: Wager
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Labotka
authors.forename: Kim
authors.initials: K
authors.lastname: Smith-Whitley
authors.forename: Alexis A
authors.initials: AA
authors.lastname: Thompson
authors.forename: Peter A
authors.initials: PA
authors.lastname: Lane
authors.forename: Lillian E C
authors.initials: LE
authors.lastname: McMahon
authors.forename: Robin
authors.initials: R
authors.lastname: Miller
authors.forename: Susan D
authors.initials: SD
authors.lastname: Roseff
authors.forename: Rathi V
authors.initials: RV
authors.lastname: Iyer
authors.forename: Lewis L
authors.initials: LL
authors.lastname: Hsu
authors.forename: Oswaldo L
authors.initials: OL
authors.lastname: Castro
authors.forename: Kenneth I
authors.initials: KI
authors.lastname: Ataga
authors.forename: Onyinye
authors.initials: O
authors.lastname: Onyekwere
authors.forename: Maureen
authors.initials: M
authors.lastname: Okam
authors.forename: Rita
authors.initials: R
authors.lastname: Bellevue
authors.forename: Scott T
authors.initials: ST
authors.lastname: Miller
mesh_terms: D056586:Acute Chest Syndrome / Q000097:blood / Q000175:diagnosis* / Q000209:etiology*; D000293:Adolescent; D000328:Adult; D000755:Anemia, Sickle Cell / Q000097:blood / Q000150:complications* / Q000175:diagnosis; D002648:Child; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D008297:Male; D054497:Phospholipases A2, Secretory / Q000097:blood*; D011379:Prognosis; D055815:Young Adult
chemical_list: D054497:Phospholipases A2, Secretory