Can Anaphylaxis Cause Elevated WBC and Neutrophil Counts?
Yes, anaphylaxis can cause elevated white blood cell (WBC) and neutrophil counts through activation of innate immune pathways and neutrophil degranulation during the acute reaction.
Mechanism of Neutrophil Involvement in Anaphylaxis
The traditional view of anaphylaxis as purely an IgE-mast cell-histamine phenomenon is incomplete. Recent evidence demonstrates that neutrophils play an active role in the pathophysiology of anaphylaxis:
Neutrophils are activated during acute anaphylaxis through both IgE-dependent and IgG-dependent pathways, contributing to the systemic inflammatory response 1, 2.
The complement system and neutrophils have been shown to be involved in anaphylaxis in human subjects, expanding our understanding beyond mast cells and basophils alone 1.
Multiple cell types contribute to anaphylaxis, including neutrophils, monocytes, macrophages, and platelets, not just mast cells and basophils 2.
Evidence from Human Studies
The most compelling evidence comes from prospective human research:
Markers of neutrophil activation are significantly elevated during acute human anaphylaxis, including S100A8, S100A9, TLR4, TREM1, MMP9, and CD64 3.
Both mRNA and protein levels of neutrophil activation markers increase during anaphylaxis, with measurements taken at emergency department arrival and at 1 and 3 hours post-onset 3.
Neutrophils undergo degranulation and NETosis (neutrophil extracellular trap formation) early after anaphylaxis onset, demonstrating active participation rather than passive elevation 4.
In a multicentric study of 86 patients with anaphylaxis to neuromuscular-blocking agents, markers of neutrophil activation correlated with anaphylaxis severity 4.
IgG-Neutrophil Pathway
An important alternative mechanism has been identified:
IgG antibodies can trigger anaphylaxis through FcγRIII and FcγRIV receptors on neutrophils, independent of the classical IgE pathway 5, 6.
This IgG-neutrophil pathway may aggravate anaphylaxis in combination with the IgE pathway or underlie anaphylaxis in the absence of specific IgE 4, 7.
Neutrophil activation can be observed in patients lacking evidence of classical IgE-dependent anaphylaxis, explaining cases where traditional markers are negative 4.
Clinical Implications
Understanding neutrophil involvement has practical significance:
Elevated WBC and neutrophil counts should not be dismissed as unrelated to anaphylaxis—they may represent active participation in the pathophysiologic process 3.
The absence of elevated tryptase or histamine does not rule out anaphylaxis, as neutrophil-mediated pathways may predominate in some cases 4.
Neutrophil activation markers (S100A8, S100A9, TREM1) correlate with anaphylaxis severity, potentially serving as additional diagnostic markers beyond traditional mast cell mediators 3.
Important Caveats
The timing of laboratory measurement matters—neutrophil activation markers peak early during the acute reaction and may normalize within hours 3.
Elevated WBC/neutrophils are not specific to anaphylaxis and can occur with many acute stress responses, infections, or inflammatory conditions, so clinical context is essential 3.
This does not change acute management—epinephrine remains first-line treatment regardless of the underlying cellular mechanism 1.