1. Standardization of Contact Factor Assays:

   The subcommittee has focused activities on standardization of contact factor assays. Contact has been made with Trevor Barrowcliff, Elaine Gray, and Tony Hubbard to obtain the SSC plasma for standardization. Initial efforts have been made toward this process.

   Plasma factor XII enzymatic and antigen assays were performed by Drs. Jones, Gallimore, and Winter of the United Kingdom. The SSC plasma was determined to contain about 1 U/ml. Drs. Schousboe and Rojkjaer of Copenhagen, Denmark, performed similar studies. There was excellent correlation between their work and the group from the United Kingdom.

   Dr. Cheryl Scott of the United States presented her efforts in determining plasma kininogen levels. Using a fluorescent antigen assay, she is able to determine plasma levels of total and high and low molecular mass kininogen. The SSC plasma contains about 60 mg/ml high molecular weight kininogen (HK). Dr. Schmaier's laboratory using coagulant and antigen assays also determined the SSC plasma to contain 1.02 U/ml and 58 mg/ml plasma HK in the SSC plasma.

   Dr. de la Cadena of the United States used an amidolytic assay to measure plasma prekallikrein in the SSC plasma. He determined it to contain 0.92 U/ml prekallikrein in plasma. Dr. Schmaier's lab, using a different assay, determined similar values, 0.92 U/ml PK activity and 33 mg/ml PK antigen in the SSC plasma.

   It was agreed among the committee that a working group be formed to begin a standardization process of contact proteins (factors XII and XI, prekallikrein, high molecular weight kininogen) of the SSC plasma. A working group (Drs. Jones, Scott, Schmaier, Schousboe) will be formed, chaired by Dr. Schmaier, to develop guidelines for plasma collection for activity and antigen assays for contact factors and to determine levels of each of the contact factors by activity (IU/ml) and antigen (mg/ml) by each of the independent forms of assays in investigators' laboratories. It is planned that each investigator will use his own pool of NHP for the standard and test the SSC plasma against this standard.

2. International Patient Registries:

   Efforts are underway to determine both retrospectively and prospectively the natural history of patients with contact protein deficiencies. National registries from Italy and Sweden were examined. Dr. Berrettini of Italy reviewed the Italian registry for evidence of contact protein deficiencies. Thirty-seven patients with homozygous deficiency (factor XII levels < 5 percent, evidence of heterozygous defects in both parents) were identified. Eighteen of these patients have a history of thrombosis; six of these patients had bleeding histories. Dr. Bylesjo of Sweden indicated that there is a Swedish registry and stated that he has begun to obtain access to this information for analysis of contact protein deficiencies.

   A working party of Drs. Schmaier, Berrettini, Bylesjo, and Castleman was created to provide guidelines for collection of data and criteria for the definition of homozygous or heterozygous deficiency of a contact protein.

3. New Assays of Contact Proteins:

   A session presented by Dr. Hasan of the United States was devoted to development of new contact protein assays based upon the developing biology and function of contact proteins. Using HK as an example, Dr. Hasan indicated how platelet aggregation, calcium mobilization studies, flow cytometry, peptide cleavage studies, and solid phase binding assays can be utilized to measure HK's thrombin inhibitory function. It was emphasized that as new biologic activities of contact proteins are appreciated, new assays to measure these proteins can be developed.

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