The Subcommittee Meeting was chaired by A. Ichinose and L. Muszbek, C.S. Greenberg and P. Board could not attend. Attendance was approximately 50 throughout the meeting. Many valuable remarks, comments and questions came from the audience, and after each presentation there was a lively discussion. The Subcommittee concentrated on four different issues:

1. Role of FXIII-A subunit polymorphism in vascular diseases.
2. Methodology and the need for standardization of FXIII assays.
3. Animal models for inflammatory bowel disease (IBD) in which the effectiveness of FXIII supplementation could be tested.
4. FXIII B-subunit deficiencies.

1.

Dr. P. Grant gave an overview of the most recent findings on FXIII-A polymorphism in different vascular diseases. Val34Leu was the only mutation among the several they tested which as a protective mutation showed (inverse) correlation with arterial diseases. It was also demonstrated that the cardioprotective effect was lost if PAI-1 level was high or if the patients had insulin resistance. The wild type was more common in DVT as well. There was an interesting discussion about the possible mechanism of the protective effect with special reference to the fact that the mutation is three amino acid residues up-stream of the thrombin cleavage-site.

2.

Dr. Muszbek gave a critical review of FXIII methodology with a proposal for the requirements of reliable FXIII assays which are aimed to be used widely in clinical laboratories. Then, he presented two new assays, sample kits are about to be distributed among interested expert laboratories for evaluation. The functional assay was a modification of the UV spectrophotometric assay based on monitoring ammonia released during the transglutaminase reaction. The antigen assay was a one-step sandwich ELISA which detected only plasma FXIII, i.e., the tetrameric complex of the two subunits, and showed remarkable sensitivity.

Dr. Jennings from UK NEQAS presented the first external quality assessment survey on FXIII determination. A relatively high number of laboratories participated and the performance of classic clot solubility test was surveyed. There was a surprising variation in the set-up of the test and accordingly the results also varied considerably. Samples from patients with severe inherited and acquired deficiencies were not recognized as abnormal by 60% and 30% of the laboratories, respectively. There was a long discussion on the use of the clot solubility test, with the general conclusion that, although it still has a place in the diagnostics of FXIII deficiencies, the general practice of using it as a "screening test" should be abandoned. UK NEQUAS was encouraged to continue the survey and to include FXIII determination in its coagulation survey profile.

Dr. Longstaff from NIBSC presented a talk on the possible developments of FXIII reference plasma. The audience highly supported the idea and the need for such a reference material was emphasised and supported. A list of participating expert laboratories is to be provided to NIBSC by the chairman of the Subcommittee.

3.

Dr. Bishop presented pieces of evidence demonstrating that dextrane sulphate-induced inflammatory bowel disease in mice could be a useful model for investigating the mechanism of beneficial effect of FXIII supplementation in IBD.

4.

Dr. Ichinose reviewed the cases of FXIII-B deficiencies and the underlying molecular genetic defects, and the classification of FXIII deficiencies was discussed.

In the general discussion it was recommended that promotion of the development of a reference plasma should be number one priority of the Subcommittee during the coming year.

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