VON WILLEBRANDS DISEASE - USE OF COLLAGEN-BINDING ASSAY PROVIDES POTENTIAL IMPROVEMENT TO LABORATORY MONITORING OF DESMOPRESSIN (DDAVP) THERAPY

This report describes studies investigating the use of a collagen binding assay to improve the laboratory monitoring of desmopressin (DDAVP) therapy in patients with von Willebrand's disease (VWD). We evaluated the response of seven patients with VWD (four type I, three type IIA) to DDAVP, administered using a standard protocol, by assessing levels of von Willebrand factor (VWF) and factor VIII, as well as performing skin bleeding times (SBT) prior to, and at sequential time points following, DDAVP administration. The study employed the following assays: von Willebrand factor antigen assay (VWF:AS; determined by ELISA); a novel functionally based collagen binding assay (CBA; determined by ELISA); ristocetin cofactor assay (RCof; determined by platelet aggregometry); von Willebrand factor multimer analysis (using SDS-agarose gels); factor VIII coagulant (FVIIIC; determined by clotting assay); and factor VIII antigen (FVIIICAG; determined by ELISA). All patients showed an initial incremental increase in vWF/FVIII levels using all assays above, and some showed some correction in SBT. Although the absolute levels of vWF/FVIII antigen or activity varied between patients, the CBA was found to provide consistently the greatest proportional incremental increases (i.e., -fold) compared to baseline (pre-DDAVP) levels. Accordingly we consistently observed an increase in the CBA to vWF:Ag ratio for all patients evaluated. This supplements previous findings that have suggested a unique ability of our CBA procedure to bind preferentially to higher molecular weight (i.e., more functionally active) forms of vWF. We therefore propose that the use of the above test combination (e.g., VWF:AS plus CBA) may provide the basis for more accurate estimation of a patient's functional responsiveness to DDAVP therapy in future studies. (C) 1994 Wiley-Liss, Inc.