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O43: Use of digoxin-specific Fab antibody fragments in two cases of life-threatening coconut crab (Birgus latro L.) poisoning - 28/06/14

Doi : 10.1016/S2352-0078(14)70051-4 
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 

Résumé

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 (760mg) 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-year-old 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 (380mg 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.
Table Abstract O43.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)NeriifolinSerum: 1.30Serum: 0.59Serum: 3.04Serum: <0.1Plasma: <0.1Whole blood: 3.17Serum: 5.01Serum: 3.90 Plasma: 4.36


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.

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© 2014  Elsevier Masson SAS. Tous droits réservés.
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Vol 26 - N° 2S

P. S25 - juin 2014 Retour au numéro
Article précédent Article précédent
  • O42: Two case-reports of intoxication with T61®, a mixture used in veterinary medecine
  • B. Lelièvre, C. Abbara, H. Benatre, S. Férec, M. Bretaudeau, C. Gegu, C. Bruneau, D. Boels, P. Harry, A. Turcant, B. Diquet
| Article suivant Article suivant
  • O44: Dosage des amatoxines (?-amanitine, ?-amanitine) et de la phalloidine dans les urines par LC-HR-MS
  • T. Gicquel, S. Lepage, O. Tribut, B. Duretz, I. Morel

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