Three Indicators Associated with Biphasic Reactions

An anaphylactic reaction can be life threatening. Fortunately, we know how to properly treat a reaction.  But what about those individuals who have a second attack, known as a biphasic reaction, without a repeat exposure to the cause of the first attack. Understanding the factors associated with biphasic reactions can lead to a better awareness and the ability to stay safe.

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Three Indicators Associated with Biphasic Reactions

By Dave Bloom of
July 1, 2022

Anaphylaxis is a severe, life-threatening reaction to a food, drug, insect venom, or environmental substance. Epinephrine is the only drug that can halt and reverse the progression of anaphylaxis and the sooner it is administered, the better the outcome.

When an individual suffers anaphylaxis they should be transported to a hospital for observation because, in an estimated 4%-6% of cases, they could suffer a second anaphylactic reaction known as a biphasic reaction without repeat exposure to the eliciting substance.

Biphasic reactions are known to be more severe than monophasic anaphylaxis, so close monitoring is recommended up to 12 hours after the initial anaphylactic reaction.

Who is at risk for a biphasic reaction? Researchers are just beginning to tease out indicators that are associated with those at increased risk.

In a letter published in the journal Clinical and Translational Allergy, researchers described their retrospective analysis of 237 patients referred for anaphylaxis to a tertiary-care university hospital between January 2017 and May 2020.

Association with Asthma

Of the 224 patients with monophasic reactions (mean age, 49.2 years; 87 men), 38 had asthma. Of the 13 patients with biphasic reactions, (mean age, 49.8 years; five men), six had asthma with a mean delay of 8 hours between the first and second reactions with a range of 1-48 hours.

Based on their data, the researchers reported increased odds of a biphasic reaction in individuals with asthma (OR = 4; 95% CI, 1.05-14.81)

Association with Loss of Consciousness

All 13 patients that suffered biphasic reactions lost consciousness during their first reaction (100%) compared with 132 (58.9%) of those with monophasic reactions (P = .008).

Association with Basal Tryptase Levels

Tryptase is a common enzyme found in the body. The patients that suffered biphasic reactions had median basal tryptase levels of 6.1 µg/L, significantly higher than the 4.2 µg/L level observed among those with monophasic reactions (P = .009).

Among the patients with asthma, those with biphasic reactions had a median basal tryptase level of 5.3 µg/L, a significant difference from those with monophasic reactions who had a level of 3.7 µg/L (P = .015).

The researchers wrote that future studies could confirm whether higher basal tryptase is a risk factor for biphasic reactions and other severe outcomes of anaphylaxis.

They indicated that their study is the first to show an association between asthma and biphasic anaphylaxis.

Severe asthma is also associated with elevated basal tryptase levels.


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