title: Platelet reactive conformation and multimeric pattern of von Willebrand factor in acquired thrombotic thrombocytopenic purpura during acute disease and remission.
abstract: BACKGROUND
  Binding of von Willebrand factor (VWF) multimers of ultra-large size to platelets is considered the triggering mechanism of microvascular thrombosis in thrombotic thrombocytopenic purpura (TTP).
  
  
  OBJECTIVE
  To assess the potential of VWF-related measurements as markers of disease activity and severity in TTP.
  
  
  METHODS
  VWF antigen (VWF:Ag), platelet glycoprotein-Ib-α binding-conformation (GPIb-α/BC) and multimeric pattern were investigated in 74 patients with acquired TTP during acute disease, remission or both and 73 healthy controls. In patients with both acute and remission samples available, VWF ristocetin co-factor activity (VWF:RCo) and collagen binding (VWF:CB) were also measured. The relationships of study measurements with the presence of acute disease and remission and with markers of disease severity were assessed.
  
  
  RESULTS
  VWF:Ag and VWF-GPIb-α/BC were higher in TTP patients than controls (P < 0.001 and 0.004). However, there was no statistically significant difference in VWF-GPIb-α/BC between samples obtained during acute TTP and remission. Larger VWF multimers were frequently lacking in acute TTP patients, who displayed ultra-large multimers at remission. The degree of loss of larger VWF multimers correlated with the degree of abnormality of hemoglobin, platelet counts and serum lactate dehydrogenase (LDH) and was associated with low levels of both VWF:RCo/Ag and VWF:CB/Ag ratios.
  
  
  CONCLUSIONS
  In TTP the platelet-binding conformation of VWF is not exclusively present in acute disease, nor is it associated with its clinical and laboratory severity. The loss of larger VWF multimers, accompanied by low VWF:RCo/Ag and VWF:CB/Ag ratio values, represents an index of disease activity and severity of acute TTP in patients with severe ADAMTS-13 deficiency.
authors: UOS Dipartimentale per la Diagnosi e la Terapia delle Coagulopatie, Angelo Bianchi Bonomi Hemophilia and Thrombosis Centre and Scientific Direction, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Fondazione Luigi Villa, Università degli Studi di Milano, Milan, Italy. luca.lotta@unimi.it
authors: L A
authors: LA
authors: Lotta
authors: R
authors: R
authors: Lombardi
authors: M
authors: M
authors: Mariani
authors: S
authors: S
authors: Lancellotti
authors: R
authors: R
authors: De Cristofaro
authors: M J
authors: MJ
authors: Hollestelle
authors: M T
authors: MT
authors: Canciani
authors: P M
authors: PM
authors: Mannucci
authors: F
authors: F
authors: Peyvandi
mesh_terms: D051722:ADAM Proteins / Q000097:blood / Q000172:deficiency; D000071120:ADAMTS13 Protein; D000208:Acute Disease; D001792:Blood Platelets / Q000502:physiology*; D016022:Case-Control Studies; D003094:Collagen / Q000097:blood; D006801:Humans; D008562:Membrane Glycoproteins / Q000097:blood / Q000737:chemistry; D019038:Platelet Glycoprotein GPIb-IX Complex; D011485:Protein Binding; D011487:Protein Conformation; D055503:Protein Multimerization; D011697:Purpura, Thrombotic Thrombocytopenic / Q000097:blood*; D012189:Retrospective Studies; D014841:von Willebrand Factor / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology*
chemical_list: D008562:Membrane Glycoproteins; D019038:Platelet Glycoprotein GPIb-IX Complex; C094990:adhesion receptor; D014841:von Willebrand Factor; D003094:Collagen; D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human