Antivenom therapy: efficacy of premedication for the prevention of adverse reactions

Morais, Víctor

doi:10.1186/s40409-018-0144-0

Cited by 33 publications

(31 citation statements)

References 35 publications

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“…Adverse reactions to antivenom may be early or late developing due to the involvement of different pathological pathways, including early developing IgE anaphylaxis, early developing non-IgE-mediated anaphylactoid reactions, and the IgG and IgM mediated late developing adverse reaction of serum sickness [ 49 , 145 , 189 , 190 , 191 , 192 , 193 , 194 , 195 , 196 , 197 , 198 ]. However, premedication with adrenalin has been shown to significantly reduce the incidence of early adverse reactions [ 193 , 199 , 200 , 201 , 202 , 203 ]. One study resulted in the contrary conclusion that adrenalin was not effective since 2 out of 11 (18%) patients receiving adrenalin had allergic responses while 20 out of 86 (23%) not receiving any form of premedication developed allergic responses [ 204 ].…”

Section: Issues and Controversies In Modern Medical Carementioning

confidence: 99%

Snakebite: When the Human Touch Becomes a Bad Touch

Fry

2018

Toxins

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Many issues and complications in treating snakebite are a result of poor human social, economic and clinical intervention and management. As such, there is scope for significant improvements for reducing incidence and increasing patient outcomes. Snakes do not target humans as prey, but as our dwellings and farms expand ever farther and climate change increases snake activity periods, accidental encounters with snakes seeking water and prey increase drastically. Despite its long history, the snakebite crisis is neglected, ignored, underestimated and fundamentally misunderstood. Tens of thousands of lives are lost to snakebites each year and hundreds of thousands of people will survive with some form of permanent damage and reduced work capacity. These numbers are well recognized as being gross underestimations due to poor to non-existent record keeping in some of the most affected areas. These underestimations complicate achieving the proper recognition of snakebite’s socioeconomic impact and thus securing foreign aid to help alleviate this global crisis. Antivenoms are expensive and hospitals are few and far between, leaving people to seek help from traditional healers or use other forms of ineffective treatment. In some cases, cheaper, inappropriately manufactured antivenom from other regions is used despite no evidence for their efficacy, with often robust data demonstrating they are woefully ineffective in neutralizing many venoms for which they are marketed for. Inappropriate first-aid and treatments include cutting the wound, tourniquets, electrical shock, immersion in ice water, and use of ineffective herbal remedies by traditional healers. Even in the developed world, there are fundamental controversies including fasciotomy, pressure bandages, antivenom dosage, premedication such as adrenalin, and lack of antivenom for exotic snakebites in the pet trade. This review explores the myriad of human-origin factors that influence the trajectory of global snakebite causes and treatment failures and illustrate that snakebite is as much a sociological and economic problem as it is a medical one. Reducing the incidence and frequency of such controllable factors are therefore realistic targets to help alleviate the global snakebite burden as incremental improvements across several areas will have a strong cumulative effect.

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Section: Issues and Controversies In Modern Medical Carementioning

confidence: 99%

Snakebite: When the Human Touch Becomes a Bad Touch

Fry

2018

Toxins

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“…This leads to difficulty in administering the correct antivenom, especially in those patients with significant coagulopathy. Although the concurrent use of two specific antivenoms may be practiced clinically, the high cost in generating antivenom, low inventory, and its side effects, such as serum sickness, should also be considered [18–21]. The correct clinical differential diagnosis between these two types of snakebites is paramount.…”

Section: Introductionmentioning

confidence: 99%

Clinical and laboratory features distinguishing between Deinagkistrodon acutus and Daboia siamensis envenomation

Huang

Mao

et al. 2018

J Venom Anim Toxins Incl Trop Dis

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BackgroundThere are 6 species of venomous snakes in Taiwan. Two of them, Deinagkistrodon acutus (D. acutus) and Daboia siamensis (D. siamensis), can cause significant coagulopathy. However, a significant proportion of patients with snakebites cannot identify the correct snake species after envenomation, which hampers the application of antivenom. Hence, the differential diagnosis between the two snakebites by clinical presentations is important. This study aims to compare their clinical and laboratory features for the purpose of differential diagnosis between the two snakebites.MethodsWe retrospectively reviewed the medical records of patients who arrived at the emergency department due to D. acutus or D. siamensis envenomation, between 2003 and 2016, in one medical center in eastern Taiwan. Since these snakebites are rare, we also included 3 cases reported from another hospital in central Taiwan.ResultsIn total, 15 patients bitten by D. acutus and 12 patients by D. siamensis were analyzed. Hemorrhagic bulla formation and the need for surgical intervention only presented for D. acutus envenomation cases (Both 53.3% vs. 0.0%, P = 0.003). As to laboratory features, lower platelet counts (20.0 × 103/μL [interquartile range, 14–66 × 103/μL] vs. 149.0 × 103/μL [102.3–274.3 × 103/μL], P = 0.001), lower D-dimer level (1423.4 μg/L [713.4–4212.3 μg/L] vs. 12,500.0 μg/L [2351.4–200,000 μg/L], P = 0.008), higher proportion of patients with moderate-to-severe thrombocytopenia (platelet count < 100 × 103/μL) (80% vs. 16.7%, odds ratio (OR) = 20.0, 95% CI, 2.77–144.31; P = 0.002), and lower proportion of patients with extremely high D-dimer (> 5000 ng/mL) (16.7% vs. 66.7%, adjusted OR = 0.1 (95% CI, 0.01–0.69; P = 0.036) were found among cases of D. acutus envenomation compared to D. siamensis envenomation. The combination of hemorrhagic bulla, thrombocytopenia, and a lack of extremely high D-dimer had good discriminatory power (area under the curve (AUC) = 0.965; 95% CI, 0.904–1.00) for distinguishing D. acutus from D. siamensis envenomation.ConclusionsThe presentation of moderate to severe thrombocytopenia (platelet count < 100 × 103/μL) and hemorrhagic bulla formation may indicate D. acutus envenomation. However, the envenomed patient with extremely high D-dimer levels may indicate a D. siamensis envenomation. These findings may help diagnose and select the right antivenom in patients with unknown snakebites who present significant coagulopathy.

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“…Non-IgE-mediated anaphylactic reactions constitute the majority of early reactions induced by therapeutic immunoglobulins. In theory, removal of the Fc portion of IgG could prevent these reactions [ 10 ]. However, various studies have shown that both IgG or F(ab’) 2 heterologous immunoglobulins can activate the complement system in vitro [ 11 , 12 ], and protein concentration and aggregation has been increasingly suggested to be the major cause of serum therapy early reactions [ 13 – 15 ].…”

Section: Introductionmentioning

confidence: 99%

Quality of horse F(ab’)2 antitoxins and anti-rabies immunoglobulins: protein content and anticomplementary activity

Squaiella-Baptistão

Magnoli

Marcelino

et al. 2018

J Venom Anim Toxins Incl Trop Dis

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BackgroundAmong other applications, immunotherapy is used for the post-exposure treatment and/or prophylaxis of important infectious diseases, such as botulism, diphtheria, tetanus and rabies. The effectiveness of serum therapy is widely proven, but improvements on the immunoglobulin purification process and on the quality control are necessary to reduce the amount of protein aggregates. These may trigger adverse reactions in patients by activating the complement system and inducing the generation of anaphylatoxins. Herein, we used immunochemical methods to predict the quality of horse F(ab’)2 anti-botulinum AB, anti-diphtheric, antitetanic and anti-rabies immunoglobulins, in terms of amount of proteins and protein aggregates.MethodsSamples were submitted to protein quantification, SDS-PAGE, Western blot analysis and molecular exclusion chromatography. The anticomplementary activity was determined in vitro by detecting the production of C5a/C5a desArg, the most potent anaphylatoxin. Data were analyzed by one-way ANOVA followed by Tukey’s post-test, and differences were considered statistically significant when p < 0.05.ResultsHorse F(ab’)2 antitoxins and anti-rabies immunoglobulin preparations presented different amounts of protein. SDS-PAGE and Western blot analyses revealed the presence of protein aggregates, non-immunoglobulin contaminants and, unexpectedly, IgG whole molecules in the samples, indicating the non-complete digestion of immunoglobulins. The chromatographic profiles of antitoxins and anti-rabies immunoglobulins allowed to estimate the percentage of contaminants and aggregates in the samples. Although protein aggregates were present, the samples were not able to induce the generation of C5a/C5a desArg in vitro, indicating that they probably contain acceptable levels of aggregates.ConclusionsAnti-botulinum AB (bivalent), anti-diphtheric, antitetanic and anti-rabies horse F(ab’)2 immunoglobulins probably contain acceptable levels of aggregates, although other improvements on the preparations must be carried out. Protein profile analysis and in vitro anticomplementary activity of F(ab’)2 immunoglobulin preparations should be included as quality control steps, to ensure acceptable levels of aggregates, contaminants and whole IgG molecules on final products, reducing the chances of adverse reactions in patients.

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Antivenom therapy: efficacy of premedication for the prevention of adverse reactions

Cited by 33 publications

References 35 publications

Snakebite: When the Human Touch Becomes a Bad Touch

Snakebite: When the Human Touch Becomes a Bad Touch

Clinical and laboratory features distinguishing between Deinagkistrodon acutus and Daboia siamensis envenomation

Quality of horse F(ab’)2 antitoxins and anti-rabies immunoglobulins: protein content and anticomplementary activity

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