Key words; complement activation, cellulose acetate, dialysis, membrances, tech support, research, standards
Complement, a series of serum proteins involved in the mediation of immune reactions, is known to be activated with implanted or external devices which encounter human blood (such as perfusion devices, columns for treating blood externally, indwelling artificial vascular grafts, and vascular shunts) . Although complement activation is an important defense mechanism of the host, particularly against microbial infections, complement activation by material components of blood-contacting devices may be harmful to the host and/or affect the function of the device. Complement activation is a tightly-regulated process which in addition to direct cell cytolysis can have profound affects on the immune, vascular, and coagulation systems. Inappropriate complement activation by blood-contacting medical devices may result in serious acute and chronic reactions.
At the request from ODE, we are conducting research to acquire base-line information, particularly needed for standards concerning the testing by industry of materials to be used in blood contacting devices. Despite the potential importance of complement activation in triggering device malfunction or patient reactions, there is no specific standard or guidance for testing for complement activation. While acquiring information on complement-related safety concerns (hazard of using dialysis membranes after prolonged shelf storage; risks associated with pulmonary/heart perfusion systems) we are developing improved standardized test procedures and reference data for guidance documents.
Using immunoassay kits and/or hemolysis assays, we plan to test a variety of blood-encountering medical devices for their effect on complement activation. The project is presently focusing on powders used in the manufacture of cellulose-acetate dialysis membranes, and fibers from new and long-storage membranes. Presently, a micro-assay for testing small amounts of device materials for complement activation has been developed, and is presently being optimized, as an inexpensive, rapid means of screening a variety of materials for complement-depleting activity. This assay is based on standard sheep RBC hemolysis techniques.