Laboratory diagnosis of von Willebrand disorder (vWD) and monitoring of DDAVP therapy: efficacy of the PFA-100 (R) and vWF : CBA as combined diagnostic strategies

We have coevaluated a combination of test processes for diagnosing von Will ebrand disease (vWD) and monitoring deamino-delta -D-arginine vasopressin ( DDAVP) therapy. Using normal controls (n = 23), closure time (CT) ranges me asured by PFA-100(R) were (mean +/- 2SD): (i) collagen/ADP cartridge (C/ADP ): 67-127 s (ii) collagen/epinephrine (C/Epi): 94-162 s. From a panel of 12 5 patients undergoing evaluation for clinical haemostatic defects, 29/30 sa mples from patients with vWD [17/18 type 1, 1/1 type 3, 3/3 type 2A, 7/7 ty pe 2B and 1/1 pseudo-vWD] gave prolonged CTs using C/Epi. The C/ADP was les s sensitive, being normal in 7/18 of the type 1 vWD individuals, with highe r sensitivity to more severe vWD. Individuals with haemophilia (six factor VIII-deficient, one factor XI-deficient) gave normal CTs, while those with clinical thrombocytopenia (n = 13) gave normal or prolonged CTs, somewhat d ependent on platelet count. The PFA-100(R) was also evaluated as a part of the laboratory monitoring procedure in patients with either vWD or haemophi lia undergoing a DDAVP trial as a therapeutic management process. For vWD, correction of an initially prolonged CT by DDAVP, accompanied by normalizat ion of von Willebrand factor (vWF) measurable by von Willebrand factor anti gen, vWF collagen binding activity and vWF ristocetin cofactor assays (vWF: Ag, vWF:CBA and vWF:RCof), was achieved in type 1 vWD (n = 5). In an indivi dual with type 2A vWD, DDAVP normalized vWF:Ag and vWF:RCof, but had no app arent effect on the baseline maximally prolonged CT. In an individual with type 2B vWD, factor VIII/vWF concentrate also normalized vWF:Ag and vWF:RCo f, but similarly had no apparent effect on the baseline maximally prolonged CT. vWF:CBA did not normalize for either of these individuals, potentially suggesting that normalization of vWF:CBA might he required for normalizati on of CT. This concept is supported by correlation analysis undertaken betw een CT and various vWF parameters. Among these, vWF:CBA held the strongest relationship in our data set, which showed an inverse progressive rise in C T for falling vWF:CBA. Based on these results, we would conclude that the P FA-100(R) is highly sensitive to the presence of vWD, and may thus provide a valuable screening test for vWD. Furthermore, the combined utility of the PFA-100(R) and vWF:CBA as markers of DDAVP responsiveness may prove to be simple, quick but powerful, predictors for its clinical efficacy.