Continuous IV Crotalidae Polyvalent Immune Fab (Ovine) (FabAV) for selected North American Rattlesnake bite patients

Bush, Sean P.; Seifert, Steven A.; Oakes, Jennifer A.; Smith, Susan D.; Phan, Tammy H.; Pearl, Sarah R.; Reibling, Ellen

doi:10.1016/j.toxicon.2013.02.008

Cited by 29 publications

(10 citation statements)

References 17 publications

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“…Another fundamental dosing issue is one of antivenom pharmacokinetics, whereby different types of antivenoms (ranging from intact immunoglobulin G to Fab fragments) have differential rates of penetration into the deep tissues and also dramatically varying rates of clearance from the body [ 213 , 214 , 215 , 216 , 217 ]. The rapid clearance rate of Fab fragment antivenoms has led to clinical issues such as recurring coagulopathy which in some cases has necessitated continuous intravenous infusion in Fab fragment antivenoms such as CroFab [ 218 , 219 , 220 , 221 , 222 , 223 ]. Further complicating matters is that venoms rich in low molecular weight toxins will be able to penetrate deeper into the tissues than antivenoms consisting of large molecular weight molecules such as intact IgG.…”

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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“… 18 , 19 Recurrent coagulopathy is almost always as severe as the presenting coagulopathy and sometimes worse. 20 In addition, new-onset late coagulopathies develop in many instances despite a full course of Fab antivenom treatment. When exactly and if coagulation abnormalities will develop and nadir are difficult to predict.…”

Section: Introductionmentioning

confidence: 99%

Comparison of F(ab’)₂versus Fab antivenom for pit viper envenomation: A prospective, blinded, multicenter, randomized clinical trial

Bush

Ruha

Seifert

et al. 2014

Clinical Toxicology

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Background. Crotalidae Polyvalent Immune Fab (Ovine) has been the only antivenom commercially available in the US since 2007 for treatment of Crotalinae envenomation. Late coagulopathy can occur or recur after clearance of Fab antivenom, often after hospital discharge, lasting in some cases more than 2 weeks. There have been serious, even fatal, bleeding complications associated with recurrence phenomena. Frequent follow-up is required, and additional intervention or hospitalization is often necessary. F(ab')2 immunoglobulin derivatives have longer plasma half life than do Fab. We hypothesized that F(ab')2 antivenom would be superior to Fab in the prevention of late coagulopathy following treatment of patients with Crotalinae envenomation. Methods. We conducted a prospective, double-blind, randomized clinical trial, comparing late coagulopathy in snakebitten patients treated with F(ab')2 with maintenance doses [F(ab')2/F(ab')2], or F(ab')2 with placebo maintenance doses [F(ab')2/placebo], versus Fab with maintenance doses [Fab/Fab]. The primary efficacy endpoint was coagulopathy (platelet count < 150 K/mm3, fibrinogen level < 150 mg/dL) between end of maintenance dosing and day 8. Results. 121 patients were randomized at 18 clinical sites and received at least one dose of study drug. 114 completed the study. Of these, 11/37 (29.7%) in the Fab/Fab cohort experienced late coagulopathy versus 4/39 (10.3%, p < 0.05) in the F(ab')2/F(ab')2 cohort and 2/38 (5.3%, p < 0.05) in the F(ab')2/placebo cohort. The lowest heterologous protein exposure was with F(ab')2/placebo. No serious adverse events were related to study drug. In each study arm, one patient experienced an acute serum reaction and one experienced serum sickness. Conclusions. In this study, management of coagulopathic Crotalinae envenomation with longer-half-life F(ab')2 antivenom, with or without maintenance dosing, reduced the risk of subacute coagulopathy and bleeding following treatment of envenomation.

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“…Despite initial bolus dosing of FabAV, the patients experienced either transient or inadequate response with profound delayed hematologic abnormalities. After initiating a continuous FabAV infusion at 2 to 4 vials per 24 hours, the hematologic derangements improved within six to fourteen days after initial injury [ 16 ].…”

Section: Discussionmentioning

confidence: 99%

Recurrent Coagulopathy after Rattlesnake Bite Requiring Continuous Intravenous Dosing of Antivenom

Hwang

Flach

2015

Case Reports in Emergency Medicine

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Context. Snakebite envenomation is common and may result in systemic coagulopathy. Antivenom can correct resulting laboratory abnormalities; however, despite antivenom use, coagulopathy may recur, persist, or result in death after a latency period. Case Details. A 50-year-old previously healthy man presented to the emergency department after a rattlesnake bite to his right upper extremity. His presentation was complicated by significant glossal and oropharyngeal edema requiring emergent cricothyrotomy. His clinical course rapidly improved with the administration of snake antivenom (FabAV); the oropharyngeal and upper extremity edema resolved within several days. However, over the subsequent two weeks, he continued to have refractory coagulopathy requiring multiple units of antivenom. The coagulopathy finally resolved after starting a continuous antivenom infusion. Discussion. Envenomation may result in latent venom release from soft tissue depots that can last for two weeks. This case report illustrates the importance of close hemodynamic and laboratory monitoring after snakebites and describes the administration of continuous antivenom infusion, instead of multidose bolus, to neutralize latent venom release and correct residual coagulopathy.

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Continuous IV Crotalidae Polyvalent Immune Fab (Ovine) (FabAV) for selected North American Rattlesnake bite patients

Cited by 29 publications

References 17 publications

Snakebite: When the Human Touch Becomes a Bad Touch

Snakebite: When the Human Touch Becomes a Bad Touch

Comparison of F(ab’)₂versus Fab antivenom for pit viper envenomation: A prospective, blinded, multicenter, randomized clinical trial

Recurrent Coagulopathy after Rattlesnake Bite Requiring Continuous Intravenous Dosing of Antivenom

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Continuous IV Crotalidae Polyvalent Immune Fab (Ovine) (FabAV) for selected North American Rattlesnake bite patients

Cited by 29 publications

References 17 publications

Snakebite: When the Human Touch Becomes a Bad Touch

Snakebite: When the Human Touch Becomes a Bad Touch

Comparison of F(ab’)2versus Fab antivenom for pit viper envenomation: A prospective, blinded, multicenter, randomized clinical trial

Recurrent Coagulopathy after Rattlesnake Bite Requiring Continuous Intravenous Dosing of Antivenom

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Comparison of F(ab’)₂versus Fab antivenom for pit viper envenomation: A prospective, blinded, multicenter, randomized clinical trial