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Cited by 526Food Allergy and Anaphylaxis ResearchMast cells and histamineDrug-Induced Adverse Reactions

Platelet-activating factor, PAF acetylhydrolase, and severe anaphylaxis

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Vadas, Peter, Gold, Milton, Perelman, Boris, Liss, Gary M., Lack, Gideon, Blyth, Thomas, Simons, F. Estelle R., Simons, Keith J. +2 more·2008·New England Journal of Medicine
DOI 10.1056/nejmoa070030
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Abstract

BACKGROUND: Platelet-activating factor (PAF) is an important mediator of anaphylaxis in animals, and interventions that block PAF prevent fatal anaphylaxis. The roles of PAF and PAF acetylhydrolase, the enzyme that inactivates PAF, in anaphylaxis in humans have not been reported. METHODS: We measured serum PAF levels and PAF acetylhydrolase activity in 41 patients with anaphylaxis and in 23 control patients. Serum PAF acetylhydrolase activity was also measured in 9 patients with peanut allergy who had fatal anaphylaxis and compared with that in 26 nonallergic pediatric control patients, 49 nonallergic adult control patients, 63 children with mild peanut allergy, 24 patients with nonfatal anaphylaxis, 10 children who died of nonanaphylactic causes, 15 children with life-threatening asthma, and 19 children with non-life-threatening asthma. RESULTS: Mean (+/-SD) serum PAF levels were significantly higher in patients with anaphylaxis (805+/-595 pg per milliliter) than in patients in the control groups (127+/-104 pg per milliliter, P<0.001 after log transformation) and were correlated with the severity of anaphylaxis. The proportion of subjects with elevated PAF levels increased from 4% in the control groups to 20% in the group with grade 1 anaphylaxis, 71% in the group with grade 2 anaphylaxis, and 100% in the group with grade 3 anaphylaxis (P<0.001). There was an inverse correlation between PAF levels and PAF acetylhydrolase activity (P<0.001). The proportion of patients with low PAF acetylhydrolase values increased with the severity of anaphylaxis (P<0.001 for all comparisons). Serum PAF acetylhydrolase activity was significantly lower in patients with fatal peanut anaphylaxis than in control patients (P values <0.001 for all comparisons). CONCLUSIONS: Serum PAF levels were directly correlated and serum PAF acetylhydrolase activity was inversely correlated with the severity of anaphylaxis. PAF acetylhydrolase activity was significantly lower in patients with fatal anaphylactic reactions to peanuts than in patients in any of the control groups. Failure of PAF acetylhydrolase to inactivate PAF may contribute to the severity of anaphylaxis.

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  • There are insufficient data to demonstrate the clinical utility of heparin, serotonin, neuropeptides, platelet-activating factor, and chromogranin A in the diagnosis of MCA and MCAS.

    “However, there are insuf fi cient data to demonstrate their clinical utility in the diagnosis of MCA and MCAS.”

    From Selecting the Right Criteria and Proper Classification to Diagnose Mast Cell Activation Syndromes: A Critical Review (2021) · cites this paper as [74]

    The Results report that serum platelet-activating factor (PAF) levels correlate with anaphylaxis severity. The Discussion calls for further study of PAF acetylhydrolase as a marker of fatal-anaphylaxis risk, but neither passage assesses the clinical utility of PAF—or the other listed substances—for diagnosing MCA or MCAS. Searches for those diagnostic terms and markers found no passage addressing that claim. (LLM, conf=0.75)

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Research works printed but not linked: 4

  1. the degradation of platelet-activating fac- tor. J Biol Chem 1987;262:4215-22.
  2. Karasawa K. Clinical aspects of plas- ma platelet-activating factor-acetylhydro- lase. Biochim Biophys Acta 2006;1761: 1359-72.
  3. Stafforini DM, Elstad MR, McIntyre TM, Zimmerman GA, Prescott SM. Hu- man macrophages secrete platelet-activat- ing factor acetylhydrolase. J Biol Chem 1990;265:9682-7.
  4. Ansley DM, Qayumi AK, Duncan S, Merrick PM, Klein R. Platelet activating factor and thromboxane B2 production af- ter cardiopulmonary bypass. J Invest Surg 1997;10:87-95.

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Authors
Vadas, P., Gold, M., Perelman, B., Liss, G. M., Lack, G., Blyth, T., Simons, F. E. R., Simons, K. J., Cass, D., & Yeung, J.
Affiliations
  • St. Michael's Hospital (CA)
  • Great Ormond Street Hospital (GB)
  • University of Toronto (CA)
  • St Mary's Hospital (GB)
  • University of Manitoba (CA)
ORCID
Lack, Gideon
Venue
New England Journal of Medicine
Publisher
Massachusetts Medical Society
Published
2008-01-03
Volume
358
Issue
1
Pages
28-35
ISSN
  • 0028-4793 (ISSN-L)
  • 1533-4406
DOI
10.1056/nejmoa070030
OpenAlex
W2133803808
Cited by
526
References
20
Citations by year
2026: 13 · 2025: 18 · 2024: 25 · 2023: 24 · 2022: 29 · 2021: 27 · 2020: 31 · 2019: 34 · 2018: 22 · 2017: 26 · 2016: 26 · 2015: 31 · 2014: 46 · 2013: 24 · 2012: 31
FWCI
25.26
Type
journal article
Language
en
Open access
Locations
  • New England Journal of Medicine (publishedVersion)
  • PubMed (publishedVersion)
  • Research Portal (King's College London) (submittedVersion)
Topics
  • Health Sciences › Medicine › Immunology and Allergy › Food Allergy and Anaphylaxis Research
  • Life Sciences › Immunology and Microbiology › Immunology › Mast cells and histamine
  • Health Sciences › Medicine › Pharmacology › Drug-Induced Adverse Reactions
Keywords
platelet-activating factor, PAF acetylhydrolase, anaphylaxis, anaphylaxis severity, peanut allergy, fatal anaphylaxis, asthma, lipid mediators, pediatric patients, life-threatening asthma, anaphylaxis prevention
MeSH terms
Adolescent, Adult, Aged, Anaphylaxis, Asthma, Child, Child, Preschool, Drug Hypersensitivity, Epinephrine, Female, Humans, Injections, Intramuscular, Insect Bites and Stings, Male, Platelet Activating Factor, Prospective Studies, Retrospective Studies, Risk Factors, Severity of Illness Index, Biomarkers, Case-Control Studies, Peanut Hypersensitivity, 1-Alkyl-2-acetylglycerophosphocholine Esterase

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