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Author Notes:

Dr L Styles, Department of Hematology/Oncology, Children’s Hospital & Research Center Oakland, 747 52nd Street, Oakland, CA 94609, USA, Tel: +1 510 428-3453, Fax: +1 510 428 3553, Email: lstyles@mail.cho.org.

The manuscript was drafted by a core writing group that consisted of Dr. Styles, Dr. Miller, and Dr. Wager.

Dr. Wager conducted the statistical analysis.

All other authors contributed substantially to the design, acquisition and interpretation of data, critical revisions of the manuscript, and approval of the final versions.

See publication for full list of individuals who were instrumental in the planning, conduct and/or care of patients enrolled in the study and the participating institutions.

The SCDCRN thanks the individuals who enrolled in the trial and their families.

The publication's contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Institutes of Health

See publication for full list of financial disclosures.

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Research Funding:

This publication was made possible by Grant Number U10HL083721 from the National Heart, Lung, and Blood Institute, National Institutes of Health.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Hematology
  • Acute chest syndrome
  • sPLA2
  • transfusion
  • vaso-occlusive episode
  • pulmonary fat embolism
  • CHRONIC TRANSFUSION THERAPY
  • PULMONARY COMPLICATIONS
  • INFLAMMATORY MEDIATORS
  • FAT-EMBOLISM
  • LUNG-DISEASE
  • RISK-FACTORS
  • PAIN CRISIS
  • A(2) LEVELS
  • CHILDREN
  • IMPACT

Refining the Value of Secretory Phospholipase A2 as a Predictor of Acute Chest Syndrome in Sickle Cell Disease: Results of a Feasibility Study (PROACTIVE)

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Journal Title:

British Journal of Haematology

Volume:

Volume 157, Number 5

Publisher:

, Pages 627-636

Type of Work:

Article | Post-print: After Peer Review

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; 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.

Copyright information:

© 2012 Blackwell Publishing Ltd.

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