Can surgical need in patients with Naja atra (Taiwan or Chinese cobra) envenomation be predicted in the emergency department?

Su, Hung-Yuan; Wang, M J; Li, Y H; Tang, CN; Tsai, Ming-Jen

doi:10.12809/hkmj154739

Cited by 13 publications

(19 citation statements)

References 11 publications

(14 reference statements)

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“…Whether FNAV has the potential to prevent local necrosis extension induced by N. atra venom has been debated for more than a decade in Taiwan [9,[11][12][13][14]. Following the standard protocol described previously [61,62] has failed to yield a mouse model of N. atra venominduced necrosis for investigating the neutralization potential of FNAV in vivo.…”

Section: Discussionmentioning

confidence: 99%

“…Cobra (N. atra) envenoming in Taiwan causes significant local tissue necrosis with swelling, in addition to inducing weak systemic neurotoxic effects [11,12]. Although the bivalent FNAV, produced by the Centers for Disease Control, ROC (Taiwan), is clinically available for treatment of cobra envenoming, the surgical intervention rate still remains high (60-65%) [11,13,14]. Despite early antivenom administration (<6 h), more than half of cobra envenoming patients develop local tissue necrosis requiring debridement or other surgical intervention [11]; thus, limits to the ability of FNAV to neutralize the cytotoxicity of N. atra have been widely discussed.…”

Section: Introductionmentioning

confidence: 99%

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Pathogenesis of local necrosis induced by Naja atra venom: Assessment of the neutralization ability of Taiwanese freeze-dried neurotoxic antivenom in animal models

et al. 2020

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Naja atra envenomation is one of the most significant clinical snakebite concerns in Taiwan. Taiwanese freeze-dried neurotoxic antivenom (FNAV) is currently used clinically for the treatment of cobra snakebite, and has been shown to limit the mortality of cobra envenomation to less than 1%. However, more than half of victims (60%) require surgery because of local tissue necrosis, a major problem in patients with cobra envenomation. Although the importance of evaluating the neutralizing effect of FNAV on this pathology is recognized, whether FNAV is able to prevent the local necrosis extension induced by N. atra venom has not been investigated in detail. Cytotoxins (CTXs) are considered as the major components of N. atra venom that cause necrosis. In the current study, we isolated CTXs from whole cobra venom and used both whole venom and purified CTXs to develop animal models for assessing the neutralization potential of FNAV against venom necrotizing activity. Local necrotic lesions were successfully produced in mice using CTXs in place of whole N. atra venom. FNAV was able to rescue mice from a subcutaneously injected lethal dose of cobra venom; however, it was unable to prevent CTX-induced dermo-necrosis. Furthermore, using the minimal necrosis dose (MND) of CTXs and venom proteome data, we found a dose of whole N. atra venom suitable for FNAV and developed a workable protocol for inducing local necrosis in rodent models that successfully imitated the clinical circumstance of cobra envenoming. This information provides a more comprehensive understanding of PLOS Neglected Tropical Diseases | https://doi.the pathophysiology of N. atra envenomation, and serves as a guide for improving current antivenom strategies and advancing clinical snakebite management in Taiwan. Author summaryNaja atra envenomation is an important public health issue in Taiwan. Although the mortality rate of cobra snakebite is controlled using antivenom, more than half of victims develop symptoms of local necrosis and require surgical intervention. Whether the Taiwanese freeze-dried neurotoxic antivenom (FNAV) currently in clinical use is able to prevent the local necrosis extension induced by N. atra venom is still unclear. In this study, we developed a dermo-necrosis animal model using purified cytotoxins (CTXs), the major necrosis-related proteins from N. atra venom. We found that FNAV was able to neutralize the lethality of whole cobra venom, but was unable to neutralize the necrosis induced by CTXs in vivo. This finding introduced an example that supplementary quality control assays may be necessary to determine the effectiveness of antivenoms in neutralizing specific pathology induced by the venom; only evaluating the rodent lethality prevention is insufficient. Our results provide insights that should help improve current antivenoms and advance cobra snakebite management in Taiwan.Pathogenesis of local necrosis induced by Naja atra venom PLOS Neglected Tropical Diseases | https://doi.org/10.The lyophilized fractions from RP-HPLC were d...

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Pathogenesis of local necrosis induced by Naja atra venom: Assessment of the neutralization ability of Taiwanese freeze-dried neurotoxic antivenom in animal models

et al. 2020

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“…We conducted a retrospective study of patient data on D. acutus and D. siamensis envenomation, who were admitted to the Hualien Tzu Chi Medical Center, the only medical center in eastern Taiwan, between 2003 and 2016. The patient data collection methodology was previously described [5, 16]. Briefly, patient medical records were collected for those admitted with snakebites, using the computerized chart system and International Classification of Diseases, 9th Revision, Clinical Modification codes 989.5, E905.0, E905.9, E906.2, and E906.5.…”

Section: Methodsmentioning

confidence: 99%

“…The main habitats of D. acutus and D. siamensis are very similar and both are distributed from the eastern to southern regions of Taiwan [3]. Victims of these two snakebite types are rare and only account for 2.4% ( D. acutus ) and 2.9% (D. siamensis ) of the total venomous snakebites in eastern Taiwan [16]. In addition to Taiwan, these two snakes are also concurrently distributed in other Southeastern Asian countries, such as Laos and Vietnam and southern China [17].…”

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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“…Naja atra , also known as Formosa or the Chinese cobra, is a highly venomous snake widely distributed in Pan-Asia and accounts for approximately 11% and 17%, respectively, of snake envenomings in Taiwan and China annually [ 1 , 2 ]. N. atra venom contains abundant three-fingered toxins (3FTXs) that contribute significantly to neurotoxic manifestations and severe local tissue damage in snakebite victims [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

Identification of Immunoreactive Peptides of Toxins to Simultaneously Assess the Neutralization Potency of Antivenoms against Neurotoxicity and Cytotoxicity of Naja atra Venom

Liu

Lin

et al. 2017

Toxins

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Assessing the neutralization capability of nonlethal but medically relevant toxins in venom has been a challenging task. Nowadays, neutralization efficacy is evaluated based simply on the survival rates of animals injected with antivenom together with a predefined dose of venom, which can determine potency against neurotoxicity but not validate the capability to neutralize cytotoxin-induced complications. In this study, a high correlation with in-vivo and in-vitro neutralization assays was established using the immunoreactive peptides identified from short-chain neurotoxin and cytotoxin A3. These peptides contain conserved residues associated with toxin activities and a competition assay indicated that these peptides could specifically block the antibody binding to toxin and affect the neutralization potency of antivenom. Moreover, the titers of peptide-specific antibody in antivenoms or mouse antisera were determined by enzyme-linked immunosorbent assay (ELISA) simultaneously, and the results indicated that Taiwanese bivalent antivenom (BAV) and Vietnamese snake antivenom-Naja (SAV-Naja) exhibited superior neutralization potency against the lethal effect of short-chain neurotoxin (sNTX) and cytotoxicity of cardiotoxin/cytotoxin (CTX), respectively. Thus, the reported peptide ELISA shows not only its potential for antivenom prequalification use, but also its capability of justifying the cross-neutralization potency of antivenoms against Naja atra venom toxicity.

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Can surgical need in patients with Naja atra (Taiwan or Chinese cobra) envenomation be predicted in the emergency department?

Cited by 13 publications

References 11 publications

Pathogenesis of local necrosis induced by Naja atra venom: Assessment of the neutralization ability of Taiwanese freeze-dried neurotoxic antivenom in animal models

Pathogenesis of local necrosis induced by Naja atra venom: Assessment of the neutralization ability of Taiwanese freeze-dried neurotoxic antivenom in animal models

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

Identification of Immunoreactive Peptides of Toxins to Simultaneously Assess the Neutralization Potency of Antivenoms against Neurotoxicity and Cytotoxicity of Naja atra Venom

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