Changes in health and disease of the metalloprotease that cleaves von Willebrand factor

• Published in: Blood Vol. 98; no. 9; pp. 2730 - 2735
• Main Authors: Mannucci, Pier Mannuccio, Canciani, Maria Teresa, Forza, Ileana, Lussana, Federico, Lattuada, Antonella, Rossi, Edoardo
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 01.11.2001; The Americain Society of Hematology
• Subjects: Adult; Age Factors; Aged; Biological and medical sciences; Biomarkers - blood; Blood coagulation. Blood cells; Female; Fundamental and applied biological sciences. Psychology; General aspects, investigation methods, hemostasis, fibrinolysis; Hematologic and hematopoietic diseases; Humans; Immunoenzyme Techniques; Infant, Newborn; Inflammation - enzymology; Liver Cirrhosis - enzymology; Male; Medical sciences; Metalloendopeptidases - blood; Middle Aged; Molecular and cellular biology; Platelet diseases and coagulopathies; Pregnancy; Purpura, Thrombotic Thrombocytopenic - diagnosis; Purpura, Thrombotic Thrombocytopenic - enzymology; Sensitivity and Specificity; Uremia - enzymology; von Willebrand Factor - metabolism; Skin disease; Pathogenesis; Hepatic disease; Metalloendopeptidases; Hemopathy; Thrombotic thrombocytopenic purpura; Hemolytic anemia; Hemostasis; Age; Human; Kidney disease; Postoperative; Nervous system diseases; Urinary system disease; Enzyme; Vascular disorders of the skin; Inflammation; Pregnancy; Peptidases; Cirrhosis; Platelet; Newborn; Renal failure; Digestive diseases; Capillary vessel disease; Hydrolases; Willebrand factor; Elderly
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V98.9.2730

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.