Quantifying the thrombogenic potential of human plasma-derived immunoglobulin products.

Polyvalent immunoglobulin G (IgG) products obtained by fractionation of human plasma are used to treat a broad range of conditions, including immunodeficiency syndromes and autoimmune, inflammatory, and infectious diseases. Recent incidences of increased thromboembolic events (TEEs) associated with intravenous (IV) IgG (IVIG) led to recalls of some products and increased regulatory oversight of manufacturing processes in order to ensure that products are essentially free of procoagulant/thrombogenic plasma protein contaminants. Laboratory investigations have now identified activated factor XI (FXIa) as the likely causative agent of IVIG-related TEEs. Quantification of the thrombogenic potential is becoming a requirement made to fractionators (a) to validate the capacity of IVIG and subcutaneous IgG manufacturing processes to remove procoagulant contaminants and (b) to establish the safety of the final products. However, in the absence of a recommended test by the main regulatory authorities, several analytical approaches have been evaluated by fractionators, regulators, and university groups. This review focuses on the scientific rationale, merits, and applications of several analytical methods of quantifying the thrombogenic potential of IgG products and intermediates to meet the latest regulatory requirements.

Two methods for the introduction of amino groups into agarose-based matrices: their use in immunoaffinity chromatography.

In this study two methods of coupling antibody to Sepharose CL2B are described. They involve the introduction of amino groups either via an amino acid such as glycine or through polyethyleneimine. After introduction of amino groups into the matrices, their activation and simultaneous fixing were accomplished by treatment with glutaraldehyde. Monoclonal antibody raised against von Willebrand factor was used as a model ligand to demonstrate the stability and performance of the affinity supports. Both methods examined in this study resulted in good retention of the antibody's binding capabilities and excellent stability of the derivatized matrices. Leaching of the insolubilized protein was considerably less with the polyethyleneimine-glutaraldehyde than with cyanogen bromide.

Three cases of metaldehyde poisoning in cattle.

Poisoning of dairy cows and of calves by metaldehyde is reported. The clinical signs, post mortem and toxicological findings are described. Confirmations of the diagnoses was obtained by biochemical estimations. It would appear that a dose as low as 0.2 g/kg in adult cattle, and even less in calves, can be lethal.