title: Central venous access device (CVAD) complications in Haemophilia with inhibitors undergoing immune tolerance induction: Lessons from the international immune tolerance study.
abstract: BACKGROUND
  Central venous access devices (CVADs) are frequently required as stable long-lasting venous access in children with haemophilia, especially those requiring immune tolerance induction (ITI) for inhibitors. CVAD infection is one of the most frequently reported catheter-related complications in this patient population.
  
  
  OBJECTIVE
  Detailed review of CVAD complications from the International ITI (I-ITI) study and analysis of potential risk factors for such complications.
  
  
  METHODS
  Retrospective analysis of prospectively obtained data from the I-ITI study primarily focused on CVAD-related complications.
  
  
  RESULTS
  A total of 115 children were recruited and 183 CVADs were placed in 99 subjects resulting in 121,206 CVAD-days observed on-study. A total of 124 CVAD infections were reported in 41 of 99 (41%) subjects with an overall infection rate of 0.94 per 1000 CVAD-days (interquartile ranges 0-1.7). A similar number of infections were observed in the two treatment arms (median: 2 and 3 in high dose and low dose respectively). Infections occurred more frequently in the presence of external catheters than with fully implanted catheters (P = 0.026). Infected patients were significantly younger at the time of CVAD insertion (median age: 22 vs. 25 months, P = 0.020). Patients with Gram-positive infections were also significantly younger than those with Gram-negative infections (median age: 17 vs. 25 months, P < 0.0001).
  
  
  CONCLUSIONS
  CVAD infection was the most common complication observed in children with severe haemophilia and inhibitors in the frame of the I-ITI study. Younger age at CVAD insertion and external CVAD were associated with higher risk for infection. ITI outcome was unaffected by CVAD infections.
authors.affiliation: Mayo Clinic Comprehensive Hemophilia Center, Rochester, MN, USA.
authors.forename: V
authors.initials: V
authors.lastname: Rodriguez
authors.affiliation: Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: M E
authors.initials: ME
authors.lastname: Mancuso
authors.affiliation: Mayo Clinic Comprehensive Hemophilia Center, Rochester, MN, USA.
authors.forename: D
authors.initials: D
authors.lastname: Warad
authors.affiliation: Department of Haematology, Manchester University, Manchester Royal Infirmary, Manchester, UK.
authors.forename: C R M
authors.initials: CR
authors.lastname: Hay
authors.affiliation: Weill Cornell Medical College, New York, NY, USA.
authors.forename: D M
authors.initials: DM
authors.lastname: DiMichele
authors.affiliation: Rush Hemophilia and Thrombophilia Center, Rush University Medical Center, Chicago, IL, USA.
authors.forename: L
authors.initials: L
authors.lastname: Valentino
authors.affiliation: National Hemophilia Center, Sheba Medical Center, Tel Hashomer, Israel.|Sackler Medical School, Tel Aviv University, Tel Hashomer, Israel.
authors.forename: G
authors.initials: G
authors.lastname: Kenet
authors.affiliation: MSU Center for Bleeding and Clotting Disorders, Michigan State University, East Lansing, MI, USA.
authors.forename: R
authors.initials: R
authors.lastname: Kulkarni
mesh_terms: D000906:Antibodies / Q000276:immunology*; D002405:Catheterization, Central Venous / Q000009:adverse effects; D002648:Child; D002675:Child, Preschool; D006467:Hemophilia A / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance; D007223:Infant; D007231:Infant, Newborn; D038622:Internationality; D016459:Prosthesis-Related Infections / Q000209:etiology; D012307:Risk Factors; D013997:Time Factors
chemical_list: D000906:Antibodies
keywords: central venous access; complications; immune tolerance; inhibitors