title: Changes in health and disease of the metalloprotease that cleaves von Willebrand factor.
abstract: Congenital or immunomediated deficiencies of the metalloprotease that cleaves physiologically von Willebrand factor (vWF) reduce or abolish the degradation of ultralarge vWF multimers that cause the formation of intravascular platelet thrombi in patients with thrombotic thrombocytopenic purpura (TTP). There is little knowledge on the behavior of the protease in other physiological and pathologic conditions. Such knowledge is important to evaluate the specificity of low protease plasma levels in the diagnosis of TTP. Using an enzyme immunoassay, the protease was measured in 177 control subjects of different ages, in 26 full-term newborns, and in 69 women during normal pregnancy. Because TTP is often associated with multiorgan involvement and acute phase reactions, clinical models of these pathologic conditions were also investigated, including decompensated liver cirrhosis (n = 42), chronic uremia (n = 63), acute inflammatory states (n = 15), and the preoperative and postoperative states (n = 24). Protease levels were lower in healthy persons older than 65 than in younger persons. They were low in newborns but became normal within 6 months, and they were lower in the last 2 trimesters of pregnancy than in the first. Protease levels were also low in patients with cirrhosis, uremia, and acute inflammation, and they fell in the postoperative period. There was an inverse relation between low protease and high plasma levels of vWF antigen and collagen-binding activity. In conclusion, low plasma levels of the vWF cleaving protease are not a specific beacon of TTP because the protease is also low in several physiological and pathologic conditions.
authors.affiliation: Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Istituto di Ricovero e Cura a Carattere Scientifico Maggiore Hospital, University of Milan, Italy. piermannuccio.mannucci@unimi.it
authors.forename: P M
authors.initials: PM
authors.lastname: Mannucci
authors.forename: M T
authors.initials: MT
authors.lastname: Canciani
authors.forename: I
authors.initials: I
authors.lastname: Forza
authors.forename: F
authors.initials: F
authors.lastname: Lussana
authors.forename: A
authors.initials: A
authors.lastname: Lattuada
authors.forename: E
authors.initials: E
authors.lastname: Rossi
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D015415:Biomarkers / Q000097:blood; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D007231:Infant, Newborn; D007249:Inflammation / Q000201:enzymology; D008103:Liver Cirrhosis / Q000201:enzymology; D008297:Male; D008666:Metalloendopeptidases / Q000097:blood*; D008875:Middle Aged; D011247:Pregnancy; D011697:Purpura, Thrombotic Thrombocytopenic / Q000175:diagnosis / Q000201:enzymology*; D012680:Sensitivity and Specificity; D014511:Uremia / Q000201:enzymology; D014841:von Willebrand Factor / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D014841:von Willebrand Factor; D008666:Metalloendopeptidases