von Willebrand factor propeptide in vascular disorders: A tool to distinguish between acute and chronic endothelial cell perturbation

Before de novo synthesized von Willebrand factor (VWF) leaves the endotheli al cell, it undergoes endoproteolytic cleavage of its propeptide (vW antige n II), The processed vWF and propeptide are either released constitutively or, following activation of the endothelium, released through the regulated pathway. In a recent study (Borchiellini et al, Blood 88:2951, 1996), we s howed that the half-life of mature vWF and of its propeptide differ fourfol d to fivefold. We postulated that the molar ratio of the propeptide to matu re vWF could serve as a tool to assess the extent of endothelial cell activ ation under physiologic and clinical conditions. To test this hypothesis, w e measured mature vWF and propeptide in patients with documented acute and chronic vascular disease, including patients with thrombotic thrombocytopen ic purpura (TTP), acute septicemia, and diabetes mellitus. These data were compared with experimental conditions in healthy subjects in which perturba tion of the endothelium was simulated by physical exercise or by administra tion of 1-deamino-8-D-arginine vasopressin (DDAVP) or endotoxin. In all ind ividuals of the latter study group, both vWF and propeptide levels were ele vated during the acute phase of the experimentally induced vascular perturb ation; at later time points after stimulation, only vWF levels remained ele vated. In patients with sepsis and TTP, both vWF and propeptide were elevat ed several-fold. Thus, this pattern can readily be explained in terms of ac ute perturbation of the endothelium. In contrast, in patients with diabetes mellitus propeptide levels were only slightly elevated, whereas vWF levels were elevated twofold to threefold. This pattern is a typical feature of c hronic, low-grade activation of the endothelium. These observations support our hypothesis that measurement of both propeptide and vWF levels allows t o discriminate between chronic and acute phases of endothelial cell activat ion in vivo. Measurement of only vWF is less indicative in this respect. (C ) 1999 by The American Society of Hematology.