Presiding chair was Robert R. Montgomery (Milwaukee, USA); all co-chairmen were present.

The attendance was approximately 425 with many individuals needing to stand.

The session was divided into five general topics ó Clinical Epidemiology, Molecular Classification, Laboratory Standardization, TTP and VWF, and Potential Future SSC Studies.

The first session on Clinical Epidemiology was introduced by Dr. S. Seremetis (New York, USA).

Dr. P. Kouides (USA) presented data on the effect of menstruation and birth control pills on VWF testing. He proposed and will carry out a study to review the approach to VWD diagnosis at participating centers with regard to women on oral contraceptives and phase of their menstrual cycle.

Dr. A. Srivastava (India) presented data on VWD testing in developing countries. He noted that these data were from specific centers in third world countries and did not necessarily reflect the availability of testing throughout these countries. Many countries did not respond and the reasons for this were discussed.

Dr. C. Miller (USA) presented data on the differences of VWF ranges in different ethnic groups and focused specifically on the African American population. Discussion included comments that absolute level, rather than normalcy range of VWF, probably predicts clinical bleeding. Dr. Sadler emphasized the misnomer of "disease" when discussing a continual variable.

Dr. C. Mazurier (France) discussed the variety of concentrates available in Europe and their differences in labeling. Most are labeled in VWF:RCo but one is labeled in VWF:CB and another in VWF:Ag. The concentrate standard was identified as important.

Dr. Federici (Italy) discussed his survey on the use of DDAVP and the lack of uniform use and availability on a world-wide basis. He proposed the development of guidelines for its use by the SSC.

The second session on Molecular Classification was introduced by Dr. J.E. Sadler (USA).

Dr. Goodeve presented the approved plans by the European Union on centralized molecular testing in Europe. The study on molecular and extragenic causes of VWD or low VWF was discussed.

Dr. D. Lillicrap (Canada) reviewed polymorphic haplotypes in type 1 VWD. These studies are going to be done collaboratively with the EU Study presented by Dr. Goodeve.

Dr. D. Ginsburg (USA) presented updates on the VWF Database. A number of deficiencies were discussed and most related to the cost and longevity of database management. Dr. Ginsburg will see if both numbering systems can be included for ease of converting. This database is voluntary and includes prepublication and non-published reports. The subcommittee will consider the need for financial support and whether this can be sought commercially.

Dr. Montgomery introduced the third session on Laboratory Standardization.

Dr. A. Hubbard (UK) discussed the recent results on the new proposed VWF concentrate standard. Although both VWF:Ag and VWF:RCo units varied when assayed against the 4^th IS Plasma Standard, most of this variability was corrected when one concentrate was compared to another using the concentrate standard. Much of the discussion focused on the collagen binding assay. A small working group was appointed to review this matter but the Concentrate Standard was recommended for SSC approval with the VWF:Ag and VWF:RCo activities as determined from his study.

Dr. R. Seitz (Germany) discussed the collagen binding standardization of concentrates using various collagens. Equine collagen appears to measure HMW preferentially compared to other collagens. The proposed European Pharmacopoeia use of collagen binding was discussed at length and it was recommended for further discussion between the ISBC, USA FDA, and interested European members.

Dr. A. Federici (Italy) discussed the need for an international standardization program. He proposed a future standardization study with a steering committee to guide its implementation. Dr. E. Preston (UK) discussed a program he was charged with to deal with third world proficiency testing. Drs. Preston and Federici will discuss this further to develop a coordinated approach rather than duplication. Since racial differences exist, it will be important to reference studies to the 4^th IS Plasma Standard.

Dr. E. Fressinaud (France) discussed the use of ratios of VWF:Ag, VWF:RCo, and FVIII in the diagnosis of type 2 VWD phenotypes. These were correlated with molecular mutations that they have discovered.

The final session on TTP and VWF Cleaving Protease, introduced by Dr. T. Raife (USA) was extensively review by Dr. H-M. Tsai (USA). This was followed by a brief discussion by Dr. S. Vesely (USA). There are considerable differences in the phenotype (HUS or TTP) relationship between some centers. Standardization of the assay and standard plasma is needed.

Dr. Montgomery concluded with a brief discussion of laboratory partnering with third world countries to improve availability of quality testing. Time limitations prevented a discussion of this in detail. Dr. Srivastava will identify countries in need and Dr. Montgomery will identify centers willing to partner.

SUMMARY OF COMMITTEE ACTIVITIES

Approval and recommendation to the full SSC that the VWF:Ag and VWF:RCo assay be accepted for 1^st Concentrate Standard and the SSC should recommend its adoption by the WHO.

For the present, the Concentrate Standard should not be labeled in VWF:CB units because of the variability of the collagens used for assay.

The committee recommends the acceptance of the VWF:CB units of the 4^th IS Standard but that this should not be used to calibrate concentrates at this time and should only be applied to plasma assays.

Ongoing projects:

Survey on diagnosis of VWD in women on oral contraceptives and varying times in their menstrual cycle.

Study of general availability of VWF testing in developing countries.

Improvement of the VWF Database through corporate sponsorship or assimilation by another database system.

Development of SSC Guidelines for the use of DDAVP in VWD.

Study of VWF in more diverse ethnic groups.

Determine if recommendations on the type of collagen used for VWF:CB should be made before wide-spread development of assays has occurred.

Continue standardization of the VWF-cleaving protease assay.

Laboratory partnering for greater availability of VWF testing worldwide.

Proposed standardization of assays VWD subtypes on a world wide basis.