O43: Use of digoxin-specific Fab antibody fragments in two cases of life-threatening coconut crab (Birgus latro L.) poisoning

O43: Use of digoxin-specific Fab antibody fragments in two cases of life-threatening coconut crab (Birgus latro L.) poisoning

Toxicologie Analytique & Clinique (2014) 26, S25-S30 Friday 13 June 2014 TOXICOLOGIE HOSPITALIÈRE, AVEC LA SFTA SESSION 1 O43 Use of digoxin-specif...

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Toxicologie Analytique & Clinique (2014) 26, S25-S30

Friday 13 June 2014

TOXICOLOGIE HOSPITALIÈRE, AVEC LA SFTA SESSION 1 O43

Use of digoxin-specific Fab antibody fragments in two cases of life-threatening coconut crab (Birgus latro L.) poisoning Y. Barguil (1, 2), C. Maillaud (2), M. Cheze (3), M. Mikulski (4), H. Le Coq Saint-Gilles (4), E. Hnawia (2), N. Lebouvier (2), G. Hoizey (3), M. Deveaux (3), G. Pepin (3), M. Nour (2) (1) Laboratoire de biochimie, CHT-NC, Nouméa ; (2) Université de la Nouvelle-Calédonie, Nouméa ; (3) Laboratoire ToxLab, Paris France ; (4) D.A.R., CHT-NC, Nouméa. Introduction. – Neriifolin is a cardenolide structurally closed to digoxin and is contained in the fruit kernel of the red-eye-sea mango tree (Cerbera manghas), on which the coconut crab feeds. We previously reported lethal neriifolin poisonings following the consumption of New Caledonian coconut crabs Birgus latro (Maillaud et al., Toxicon 2010). This led us to consider digoxin-specific Fab antibody fragments (Fab) as a specific treatment. This presentation focuses on two cases of successful Fab use. Methods. – Case #1 (Maillaud et al., Toxicon 2012): a 63-year-old female was admitted to the ER. She had eaten a coconut crab 19 hours previously. ECG showed first-degree atrio-ventricular block (AVB), specific repolarisation abnormalities and prolonged cardiac pauses. Fab (760 mg) were then administered intravenously 21 hours after the toxic meal. No more cardiac pause was reported and the patient was discharged one week later. Case #2: a 73-yearold man complained of vomiting after having eaten a coconut crab a few hours before. He was admitted to the ER. ECG monitoring showed bradycardia (32 to 45 beats/min), arrhythmia and cardiac pauses. Fab were administered (380 mg IV = 10 units). 10 other units were administered 3 hours later in the ICU. Cardiac pauses disappeared and cardiac frequency went close to normal. The patient was discharged at day 2. Different blood samples were analysed. Neriifolin was determined by LC-IT-MS/MS.

Results. – Neriifolin blood concentrations (ng/mL): In both cases, neriifolin concentrations increased after the Fab perfusions. As digoxin, neriifolin leaves cardiac receptors to be bound to Fab fragments, and is then eliminated. Surprisingly, as shown in case #2, neriifolin whole blood concentration is much higher than in serum and in plasma. Like digoxin, haemoglobin could be the neriifolin binding site in blood. This may implicates that in cardenolides poisoning, low serum and plasma concentrations should be considered with caution. Two other C. manghas cardenolides of interest: cerberigenin and cerberin, were not detected in all nine samples. Conclusion. – Digoxin-specific Fab antibody fragments have been effective in the treatment of two life-threatening coconut crab poisonings. Such therapy should be considered in patients showing heart conduction disturbances. As with digoxin, in each case we note a rise in total (free + bound) neriifolin blood concentrations after antidote administration. In Case #2 whole blood concentration was more than 30 times higher than serum and plasma concentrations. To avoid false negative results we suggest considering also whole blood analysis in case of suspected cardenolide intoxications. Reversibility of the RBC partitioning has been shown for digoxin and haemoglobin could be a storage compartment for neriifolin which would explain the need for the supplemental Fab dose in Case #2. O44

Dosage des amatoxines (α-amanitine, β-amanitine) et de la phalloidine dans les urines par LC-HR-MS

T. Gicquel (1), S. Lepage (1), O. Tribut (2), B. Duretz (3), I. Morel (1) (1) Laboratoire de toxicologie biologique et médico-légale, CHU Pontchaillou, Rennes, France ; (2) UF Biomarqueurs, CHU Pontchaillou, Rennes, France ; (3) Thermo Fisher, Courtaboeuf, France. Introduction. – Les intoxications par les champignons chez l’homme mettent souvent en jeu les espèces appartenant aux genres Amanita ou Galerina. Les toxines responsables sont les amatoxines, telles que l’α-amanitine, la β-amanitine ou des phallotoxines, comme la phalloïdine, retrouvée chez Amanita phalloides. Afin d’identifier ces intoxications par les champignons et d’en estimer l’ampleur, nous avons développé une méthode de dosage des amatoxines et de la

Table Abstract O43

Neriifolin

Case #1 (admission)

Case #1 (ICU before Fab)

Case #1 (12h after Fab)

Case #2 (2h after 1st Fab)

Case #2 (5h after 2nd Fab)

Case #2 (8h after 2nd Fab)

Serum: 1.30

Serum: 0.59

Serum: 3.04

Serum: <0.1 Plasma: <0.1 Whole blood: 3.17

Serum: 5.01

Serum: 3.90 Plasma: 4.36

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