Analyze the need for standardized methods to measure contact activation during extracorporeal circulation and hemofiltration.

The subcommittee has focused on this topic as extracorporeal circulation, hemofiltrations, and artificial valves and joints are all procoagulant surfaces for contact activation. The degree of activation of the system significantly influences the non-specific reactions that support systemic inflammatory responses and hemostatic perturbation. Precautions are being taken therefore to minimize contact activation by increasing the biocompatibility of the artificial device. However, the necessity to respect the integrity of the organism during the procedure precludes most systemic interventions and limits the control of blood activation on the area of the device.

The presentations by Dr. Olsson, et al. from Sweden and Dr. te Velthuis, et al. from Holland in combination with our knowledge from the literature suggest the need for proper assays to follow the degree of activation during and after extracorporeal circulation.

It was agreed among the committee that a working group (Dr. Berrettini, Dr. De La Cadena, Dr. Lämmle, Dr. Saito, Dr. Schmaier and Dr. Schousboe) be formed to begin standardization of contact activation proteins (Factor XII, Factor XI, prekallikrein and high molecular mass kininogen). Levels of each of the contact factors by activity and antigen will be measured. It is planned that each investigator uses his/her own pool of NHP for standard and test the SSC plasma against this standard. In this context, the subcommittee contacted Dr. Jane Lenahan and Dr. Anthony Hubbard (National Institute for Biological Standards and Control) and arranged for delivery of the standard. The committee also agreed to look further into assays for Factor XIIa.

The efforts taken two years ago to determine retrospectively and prospectively the medical history of patients with contact protein deficiency was updated. Dr. Bylesjo from Sweden, Dr. Dalsgaard-Nielsen from Denmark, Drs. Berrettini and Castaman from Italy and Dr. Lammle et al. from Switzerland all agreed that there is no correlation between non-severe Factor XII deficiency (2-50% of normal Factor XII) and thromboembolic events. There seems to be indication of a correlation between severe factor deficiency (<2%) and arterial, rather than venous thrombosis. The report from Dr. Dalsgaard-Nielsen indicated that there seems to be a higher risk of thrombosis among patients with LA and antiphospholipid antibodies directed against Factor XII compared to the risk connected with the presence of other antiphospholipid antibodies. The committee agreed to look further into this possibility.

The committee also agreed to analyze the statistical need for investigating whether severe Factor XII deficiency is connected with increased risk of thrombosis. Dr. Berrettini will be in charge of this investigation.