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: Lori Styles, Carrie G Wager, Richard J Labotka, Kim Smith-Whitley, Alexis A Thompson, Peter A Lane, Lillian E C McMahon, Robin Miller, Susan D Roseff, Rathi V Iyer, Lewis L Hsu, Oswaldo L Castro, Kenneth I Ataga, Onyinye Onyekwere, Maureen Okam, Rita Bellevue, Scott T Miller, Sickle Cell Disease Clinical Research Network (SCDCRN)
• Journal: British journal of haematology (Br J Haematol) Vol. 157 Issue 5 Pg. 627-36 (Jun 2012) ISSN: 1365-2141 [Electronic] England
• PMID: 22463614 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2012 Blackwell Publishing Ltd.

Chemical References

• Phospholipases A2, Secretory

Topics

• Acute Chest Syndrome (blood, diagnosis, etiology)
• Adolescent
• Adult
• Anemia, Sickle Cell (blood, complications, diagnosis)
• Child
• Feasibility Studies
• Female
• Humans
• Male
• Phospholipases A2, Secretory (blood)
• Prognosis
• Young Adult