Refining the value of secretory phospholipase A2 as a predictor of acute chest syndrome in sickle cell disease: results of a feasibility study (PROACTIVE)

• Published in: British journal of haematology Vol. 157; no. 5; pp. 627 - 636
• Main Authors: Styles, Lori, Wager, Carrie G., Labotka, Richard J., Smith-Whitley, Kim, Thompson, Alexis A., Lane, Peter A., McMahon, Lillian E. C., Miller, Robin, Roseff, Susan D., Iyer, Rathi V., Hsu, Lewis L., Castro, Oswaldo L., Ataga, Kenneth I., Onyekwere, Onyinye, Okam, Maureen, Bellevue, Rita, Miller, Scott T.
• Format: Journal Article
• Language: English
• Published: Oxford Blackwell Publishing Ltd 01.06.2012; Blackwell
• Subjects: Acute chest syndrome; Acute Chest Syndrome - blood; Acute Chest Syndrome - diagnosis; Acute Chest Syndrome - etiology; Adolescent; Adult; Anemia, Sickle Cell - blood; Anemia, Sickle Cell - complications; Anemia, Sickle Cell - diagnosis; Anemias. Hemoglobinopathies; Biological and medical sciences; Child; Diseases of red blood cells; Feasibility Studies; Female; Hematologic and hematopoietic diseases; Humans; Male; Medical sciences; Phospholipases A2, Secretory - blood; Pneumology; Prognosis; pulmonary fat embolism; Pulmonary hypertension. Acute cor pulmonale. Pulmonary embolism. Pulmonary vascular diseases; sPLA2; transfusion; vaso-occlusive episode; Young Adult; Hemoglobinopathy; Sickle cell anemia; Transfusion; Fat embolism; Hematology; Enzyme; Respiratory disease; pulmonary fat embolism; vaso-occlusive episode; Cardiovascular disease; Esterases; Hemopathy; Acute chest syndrome; Phospholipase A; Carboxylic ester hydrolases; Genetic disease; Vascular disease; Pulmonary embolism; Hemolytic anemia; Hydrolases; Feasibility; sPLA2; Predictive factor
• ISSN: 0007-1048; 1365-2141; 1365-2141
• DOI: 10.1111/j.1365-2141.2012.09105.x

Summary 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.