Comparative study of the efficacy and safety of two polyvalent, caprylic acid fractionated [IgG and F(ab')2] antivenoms, in Bothrops asper bites in Colombia.

Abstract

The efficacy and safety of two polyvalent horse-derived antivenoms in Bothrops asper envenomings were tested in a randomized, double-blind, clinical trial performed in Colombia. Both antivenoms were manufactured from the same pool of hyperimmune plasma. Antivenom A was made of F(ab')2 fragments, generated by pepsin digestion and caprylic acid precipitation, whereas antivenom B consisted of whole IgG molecules produced by caprylic acid precipitation followed by ion-exchange chromatography. Besides the different nature of the active substance, antivenom B had higher protein concentration, slightly higher turbidity and aggregate content. No significant differences were observed in the efficacy of antivenoms. Both halted local and systemic bleeding (P = 0.40) within 6-12 h of treatment in 100% of the cases, and restored blood coagulation (P = 0.87) within 6-24 h in 84.7% of patients, and within 48 h in all of them, in agreement with restoration of plasma fibrinogen concentration. Venom concentrations in serum dropped significantly (P < 0.001), to very low levels, 1 h after antivenom infusion. Nevertheless, eight patients (11.1%), four for each antivenom, presented recurrence of venom antigenaemia at different times, from 6 to 96 h, with clinical significance (recurrent coagulopathy) only in one group B patient (2.9%). Serum creatine kinase (CK) activity was increased, as a consequence of local myonecrosis. There was no significant difference (P = 0.51) in the incidence of early adverse reactions to antivenom administration (28.9% for patients of group A and 20.6% for patients of group B), most of the reactions being mild, mainly cutaneous. The most frequent complications were cellulitis (16.7%), abscess formation (5.6%), acute renal failure (8.3%), and compartmental syndrome (5.6%). In conclusion, IgG and F(ab')2 antivenoms, prepared by caprylic acid fractionation, presented similar efficacy and safety profiles for the treatment of B. asper envenomings in Colombia.

• Authors: Rafael Otero-Patiño, Alvaro Segura, María Herrera, Yamileth Angulo, Guillermo León, José María Gutiérrez, Jacqueline Barona, Sebastián Estrada, Andrés Pereañez, Juan Carlos Quintana, Leidy J Vargas, Juan Pablo Gómez, Abel Díaz, Ana María Suárez, Jorge Fernández, Patricia Ramírez, Patricia Fabra, Monica Perea, Diego Fernández, Yobana Arroyo, Dalila Betancur, Lady Pupo, Elkin A Córdoba, C Eugenio Ramírez, Ana Berta Arrieta, Alcides Rivero, Diana Carolina Mosquera, Nectty Lorena Conrado, Rosina Ortiz
• Journal: Toxicon : official journal of the International Society on Toxinology (Toxicon) Vol. 59 Issue 2 Pg. 344-55 (Feb 2012) ISSN: 1879-3150 [Electronic] England
• PMID: 22146491 (Publication Type: Comparative Study, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Ltd. All rights reserved.

Chemical References

• Antivenins
• Caprylates
• Crotalid Venoms
• Immunoglobulin Fab Fragments
• Immunoglobulin G
• Fibrinogen
• Pepsin A
• octanoic acid

Topics

• Adolescent
• Animals
• Antivenins (therapeutic use)
• Blood Coagulation
• Blood Coagulation Disorders (drug therapy)
• Bothrops (metabolism)
• Caprylates (pharmacology)
• Chemical Fractionation (methods)
• Chromatography, Ion Exchange (methods)
• Colombia
• Crotalid Venoms (metabolism)
• Double-Blind Method
• Drug Evaluation
• Drug-Related Side Effects and Adverse Reactions (metabolism)
• Female
• Fibrinogen (analysis)
• Hemorrhage (drug therapy)
• Humans
• Immunoglobulin Fab Fragments (therapeutic use)
• Immunoglobulin G (therapeutic use)
• Incidence
• Male
• Pepsin A (metabolism)
• Snake Bites (drug therapy)
• Treatment Outcome