title: Assessment of Anti-Tissue Type Plasminogen Activator Antibodies in Patients With Prosthetic Heart Valve Thrombosis: The ATA Trial.
abstract: Thrombolysis is an effective treatment strategy for prosthetic valve thrombosis (PVT). Recombinant tissue-type plasminogen activator (rt-PA) is widely used as a thrombolytic agent. Infusion of rt-PA may trigger the production of anti-tissue plasminogen activator (tPA) antibodies (ATAs). We aimed to evaluate the possible relationship between ATA levels and PVT formation, and the role of baseline ATA levels on outcomes of thrombolytic therapy in patients with PVT.
  
  
  
  This prospective, single-center cohort study included 28 patients with PVT undergoing thrombolysis and 31 controls with normal prostheses. Plasma samples were collected from patients with PVT at baseline and at 15th, 30th, 90th, and 180th days after thrombolysis and from controls at baseline only. The ATA levels were assessed in human plasma by an enzyme-linked immunosorbent assay.
  
  
  
  Baseline ATA-immunoglobulin (Ig) G and IgM were significantly higher in patients with PVT than in controls. The levels of IgM and IgG peaked at 15th and 30th days after rt-PA infusion, respectively. Subtherapeutic international normalized ratio and baseline ATA-IgM were independent predictors of PVT. Thrombolysis failed in 6 patients (21%) in whom baseline IgM levels were significantly higher than successfully lysed patients. Rethrombosis occurred in 9 patients (32%) in whom baseline IgG levels were significantly higher than those without rethrombosis. There was a moderate positive correlation between baseline and 15th-day IgM levels and the dose of rt-PA needed for successful lysis.
  
  
  
  The ATA levels tended to be higher in patients with PVT at the time of initial diagnosis compared to controls without PVT. In addition, such patients with PVT and high ATA levels may be at high risk for failed thrombolysis or rethrombosis.
authors.affiliation: Division of Health Sciences, University of Ardahan, Ardahan, Turkey Department of Cardiology, Kosuyolu Kartal Heart Training and Research Hospital, İstanbul, Turkey.
authors.forename: Mehmet
authors.initials: M
authors.lastname: Özkan
authors.affiliation: Department of Cardiology, Kosuyolu Kartal Heart Training and Research Hospital, İstanbul, Turkey macitkalcik@yahoo.com.
authors.forename: Macit
authors.initials: M
authors.lastname: Kalçık
authors.affiliation: Department of Cardiology, Kosuyolu Kartal Heart Training and Research Hospital, İstanbul, Turkey.
authors.forename: Mustafa Ozan
authors.initials: MO
authors.lastname: Gürsoy
authors.affiliation: Department of Cardiology, Kosuyolu Kartal Heart Training and Research Hospital, İstanbul, Turkey.
authors.forename: Lütfi
authors.initials: L
authors.lastname: Öcal
authors.affiliation: Department of Internal Medicine, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy.
authors.forename: Samantha
authors.initials: S
authors.lastname: Griffini
authors.affiliation: Division of Health Sciences, University of Ardahan, Ardahan, Turkey.
authors.forename: Süleyman
authors.initials: S
authors.lastname: Karakoyun
authors.affiliation: Department of Cardiology, Kosuyolu Kartal Heart Training and Research Hospital, İstanbul, Turkey.
authors.forename: Mahmut
authors.initials: M
authors.lastname: Yesin
authors.affiliation: Department of Cardiology, Kosuyolu Kartal Heart Training and Research Hospital, İstanbul, Turkey.
authors.forename: Sabahattin
authors.initials: S
authors.lastname: Gündüz
authors.affiliation: Department of Cardiology, Kosuyolu Kartal Heart Training and Research Hospital, İstanbul, Turkey.
authors.forename: Mehmet Ali
authors.initials: MA
authors.lastname: Astarcıoğlu
authors.affiliation: Department of Cardiology, Kosuyolu Kartal Heart Training and Research Hospital, İstanbul, Turkey.
authors.forename: Emrah
authors.initials: E
authors.lastname: Bayam
authors.affiliation: Department of Cardiology, Kosuyolu Kartal Heart Training and Research Hospital, İstanbul, Turkey.
authors.forename: Sinan
authors.initials: S
authors.lastname: Cerşit
authors.affiliation: Department of Cardiology, Kosuyolu Kartal Heart Training and Research Hospital, İstanbul, Turkey.
authors.forename: Ahmet Çağrı
authors.initials: AÇ
authors.lastname: Aykan
authors.affiliation: Department of Internal Medicine, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Cugno
mesh_terms: D000328:Adult; D000368:Aged; D000906:Antibodies / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D006349:Heart Valve Diseases / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology; D006350:Heart Valve Prosthesis; D019918:Heart Valve Prosthesis Implantation / Q000009:adverse effects* / Q000295:instrumentation*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood*; D007075:Immunoglobulin M / Q000097:blood*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011446:Prospective Studies; D012008:Recurrence; D012307:Risk Factors; D015912:Thrombolytic Therapy / Q000009:adverse effects / Q000379:methods*; D013927:Thrombosis / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000906:Antibodies; D015415:Biomarkers; D005343:Fibrinolytic Agents; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D010959:Tissue Plasminogen Activator
keywords: echocardiography; heart valve prosthesis; thrombolytic therapy; thrombosis; tissue plasminogen activator