Dysfibrinogens

Dr. Hanss (France) summarized the current content of the on-line database of dysfibrinogens, which he compiled, and that is now also available on the ISTH web site. He described the specific information associated with each case in this database. Dr. Hanss proposed developing a form for on-line submission of further entries to the database. It was agreed that Dr. Hanss should moderate and update this data base. Investigators should submit new dysfibrinogens on-line to Dr. Hanss. As this database may provide the basis to associate specfic structural changes with clinical symptoms, the subcommittee encouraged Dr. Hanss to include a description of the clinical data available for each patient and family member.

Fibrinogen in mice

Dr. Lord (USA) presented data on the potentially significant variations in "normal" plasma fibrinogen levels in laboratory mice, which appear to vary with diet, age and mouse strain. The mouse model is commonly used in experimental studies that relate fibrinogen levels to a variety of disease states. There appeared to be a concensus that standardization of the measurement of plasma fibrinogen in mice would be desireable. Dr. Lord undertook to return to the Subcommittee with proposals for a standardization exercise. The proposals will include a method to draw blood, specifying an anticoagulant, and the assay method itself (e.g, ELISA). A reference preparation for mouse plasma would be a desirable aspect of the standardization. The mouse standard would be related to previous functional measurements of either human or mouse fibrinogen.

Fibrinogen plasma standards

Dr. Weinstock (Germany) summarized the critical features of his subcommittee report that described the proposed high fibrinogen reference plasma. Dr. Weinstock also showed further results on the potential use of such a preparation in clinical laboratory measurements. Dr. Lord confirmed that Dr. Weinstockís report has been received and she indicated that this report had been reviewed by expert members of the Subcommittee. (Note added after the meeting: the statement made by the chair that the review process was complete was incorrect, as in fact, the review process is ongoing. This position will be clarified with Dr. Weinstock and Dr. Padilla, WHO, who was present at the meeting.)

Standardization of the measurement of components in fibrin sealants

Dr. McIntosh (UK) reported that it was his understanding that the revision of the fibrin sealant monograph is still under consideration by the European Pharmacopia.

Dr. McIntosh (UK) summarized the steps taken to approve the report from Dr. Barrowcliffe (UK) on the collaborative study (initiated by the SSC Fibrinogen subcommittee in 1999) to establish an international standard for fibrinogen concentrate. The WHO has adopted the recommended preparation from this report as the First International Fibrinogen Concentrate Stardard. Dr. Lord will report on this procedure to this yearís SSC Annual Business Meeting.

Dr. Longstaff (UK) and Dr. Chang (USA) presented a proposal to characterize and calibrate a new reference preparation for thrombin. Thrombin is a key component of Fibrin Sealant kits and the subcommittee had previously decided to provide continuity by considering the standardization of other Fibrin Sealant components in addition to fibrinogen. The proposal from Drs. Longstaff and Chang was generally accepted with specific agreement that 100IU/vial was sufficient for a reference preparation; an intermediate purity preparation formulated in human albumin would be acceptable; results from a functional assay (thrombin/fibrinogen clotting time) would be preferred in assaying the potency and the calibration should be carried out against both existing NIH and WHO reference materials. The calibration of thrombin activity using clotting time should use the First International Fibrinogen Concentrate Standard, or material calibrated against that standard. The remaining stocks of the NIH and WHO thrombin standards are low, so there is an urgent need to establish a new reference material. Thus, Drs. Longstaff and Chang will report on their progress to next yearís SSC meeting in Boston.

On behalf of Dr. Barrowcliffe (UK), who was detained at another subcommittee meeting, Dr. McIntosh presented summary slides on the progress of proposals to establish reference materials for the measurement of FXIII. These proposals will also be discussed at the FXIIII subcommittee meeting. The purpose of presenting them here was to determine whether or not there would be value in including a candidate preparation that could be used for the measurement of FXIII in Fibrin Sealent kits. It was agreed that the Fibrinogen Subcommittee would welcome the opportunity to work with the FXIII Subcommittee on this study. Furthermore, it was suggested that the inclusion of a preparation to determine if FXIII can be accurately measured in a concentrated solution of fibrinogen would be particularly useful. In addition to the assay methods proposed by Dr. Barrowcliffe, data on measuring FXIII using the solubility of fibrin in a suitable solvent, e.g., urea or chloroacetic acid (the latter is reference method in the Fibrin Sealant Monograph), would also be useful.