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.

Phycomyces: detailed analysis of the anemogeotropic response.

Stage IVb sporangiophores of Phycomyces grow into the wind--the anemotropic response--and away from gravity--the geotropic response. A procedure has been designed to measure the equilibrium bend angle that results when the two stimuli are given simultaneously over a long period of time. This angle will be referred to as the anemogeotropic equilibrium angle. This measurement of a sensory response is analogous to the photogeotropic equilibrium angle in which the variable stimulus is light instead of wind. We have found that the anemogeotropic angle, measured relative to the vertical, increases with both increasing wind speed and increasing relative humidity of the wind stimulus. This finding is new and argues against a major prediction of the mass transfer model that anemogeotropism and relative humidity are inversely related. Data from these anemogeotropic experiments further suggest that the self-emitted gas responsible for both the anemotropic response and the avoidance response is water.