title: Clinical and prognostic significance of serum levels of von Willebrand factor and ADAMTS-13 antigens in AL amyloidosis.
abstract: Cardiac dysfunction determines prognosis in amyloid light-chain (AL) amyloidosis. The heart is the central organ of the vascular system in which endothelium function is critical for the circulatory homeostasis, but there are limited data on endothelial function in AL amyloidosis. von Willebrand factor (VWF) has been considered as a marker of endothelial activation and dysfunction, whereas a disintegrin and metalloproteinase with thrombospondin type-1 repeats 13 (ADAMTS-13) cleaves VWF multimers, but both have been associated with prognosis in cardiovascular disease. We measured the serum levels of VWF (VWF:Ag) and ADAMTS-13 antigens in 111 newly diagnosed patients with AL amyloidosis. The levels of VWF:Ag were significantly higher than in healthy controls; 76% of patients with AL had VWF:Ag levels higher than the upper levels of controls. There was no significant association of VWF:Ag levels with patterns of organ involvement, free light-chain levels, the levels of cardiac biomarkers, or renal dysfunction but correlated with low systolic blood pressure. VWF:Ag levels ≥230.0 U/dL were associated with higher probability of early death and poor survival independently of cardiac biomarkers and low systolic blood pressure (SBP). Moreover, among patients with Mayo stage III or stage IIIB (that is stage III with N-terminal pro-brain natriuretic peptide [NTproBNP] >8500 pg/mL) disease, VWF:Ag identified subgroups of patients with very poor outcome. Low ADAMTS-13 levels correlated with high levels of NTproBNP but had no independent prognostic significance. In conclusion, high VWF:Ag levels, probably representing endothelial dysfunction, are associated with prognosis in patients with AL amyloidosis, independently of other features of the disease or cardiac biomarkers.
authors.affiliation: Department of Clinical Therapeutics, National and Kapodistrian University of Athens School of Medicine, Athens, Greece;
authors.forename: Efstathios
authors.initials: E
authors.lastname: Kastritis
authors.affiliation: Department of Clinical Biochemistry, and.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Papassotiriou
authors.affiliation: Department of Clinical Therapeutics, National and Kapodistrian University of Athens School of Medicine, Athens, Greece;
authors.forename: Evangelos
authors.initials: E
authors.lastname: Terpos
authors.affiliation: Department of Clinical Therapeutics, National and Kapodistrian University of Athens School of Medicine, Athens, Greece;
authors.forename: Maria
authors.initials: M
authors.lastname: Roussou
authors.affiliation: Department of Clinical Therapeutics, National and Kapodistrian University of Athens School of Medicine, Athens, Greece;
authors.forename: Maria
authors.initials: M
authors.lastname: Gavriatopoulou
authors.affiliation: Hemostasis Unit, Hemophilia Centre, Aghia Sophia Children's Hospital, Athens, Greece;
authors.forename: Anna
authors.initials: A
authors.lastname: Komitopoulou
authors.affiliation: Department of Clinical Biochemistry, and.
authors.forename: Chrysanthi
authors.initials: C
authors.lastname: Skevaki
authors.affiliation: Department of Clinical Therapeutics, National and Kapodistrian University of Athens School of Medicine, Athens, Greece;
authors.forename: Evangelos
authors.initials: E
authors.lastname: Eleutherakis-Papaiakovou
authors.affiliation: Department of Clinical Therapeutics, National and Kapodistrian University of Athens School of Medicine, Athens, Greece;
authors.forename: Constantinos
authors.initials: C
authors.lastname: Pamboucas
authors.affiliation: Department of Clinical Therapeutics, National and Kapodistrian University of Athens School of Medicine, Athens, Greece;
authors.forename: Erasmia
authors.initials: E
authors.lastname: Psimenou
authors.affiliation: Department of Clinical Therapeutics, National and Kapodistrian University of Athens School of Medicine, Athens, Greece;
authors.forename: Efstathios
authors.initials: E
authors.lastname: Manios
authors.affiliation: Second Department of Internal Medicine, National and Kapodistrian University of Athens School of Medicine, Athens, Greece;
authors.forename: Stavroula
authors.initials: S
authors.lastname: Giannouli
authors.affiliation: Hematology Laboratory, Blood Bank, Aretaieion Hospital, Athens, Greece;
authors.forename: Marianna
authors.initials: M
authors.lastname: Politou
authors.affiliation: First Department of Pathology, National and Kapodistrian University of Athens School of Medicine, Athens, Greece; and.
authors.forename: Harikleia
authors.initials: H
authors.lastname: Gakiopoulou
authors.affiliation: Department of Clinical Therapeutics, National and Kapodistrian University of Athens School of Medicine, Athens, Greece;
authors.forename: Elektra
authors.initials: E
authors.lastname: Papadopoulou
authors.affiliation: Department of Clinical Therapeutics, National and Kapodistrian University of Athens School of Medicine, Athens, Greece;
authors.forename: Kimon
authors.initials: K
authors.lastname: Stamatelopoulos
authors.affiliation: Department of Haemopathology, Evangelismos Hospital, Athens, Greece.
authors.forename: Anna
authors.initials: A
authors.lastname: Tasidou
authors.affiliation: Department of Clinical Therapeutics, National and Kapodistrian University of Athens School of Medicine, Athens, Greece;
authors.forename: Meletios A
authors.initials: MA
authors.lastname: Dimopoulos
mesh_terms: D000071120:ADAMTS13 Protein / Q000097:blood*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000686:Amyloidosis / Q000097:blood* / Q000503:physiopathology; D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure; D005260:Female; D006801:Humans; D007147:Immunoglobulin Light Chains / Q000097:blood; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood; D009928:Organ Specificity; D010446:Peptide Fragments / Q000097:blood; D014841:von Willebrand Factor / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D007147:Immunoglobulin Light Chains; D010446:Peptide Fragments; C109794:pro-brain natriuretic peptide (1-76); D014841:von Willebrand Factor; D020097:Natriuretic Peptide, Brain; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human