title: Symptomatic thromboembolic events in patients treated with intravenous-immunoglobulins: results from a retrospective cohort study.
abstract: OBJECTIVE
  To estimate the incidence and predictors of symptomatic arterial and venous thromboembolic events (TEE) from intravenous immunoglobulin (IVIg) therapy according to its indications.
  
  
  METHODS
  We performed a retrospective cohort study of patients seen at our institution and treated with IVIg over a 36-month period. Indications, comorbility and comedication associated with TEE were identified by a stepwise logistic regression analysis.
  
  
  RESULTS
  Of 303 patients included with at least one infusion of IVIg over three years, TEE were identified in a total of 50 patients treated with IVIg, for an incidence of 16.9% (CI 95%: 13.0-21.6); 27 (54%) arterial (9.1%;CI 95%: 6.3-13.0%) and 23 (46%) venous TEE (7.8%; CI95%: 5.2-11.4%), overall mortality was 32%. Per indication there were more patients with autoimmune conditions, secondary immunodeficiency, dysimmune neuropathies, acute rejection of solid organ transplantation and sepsis. Patients with TEE were significantly older, were more likely to be men, they had more comorbid conditions; the doses of IVIg were high (589.4mg/kg/day vs 387.0mg/kg/day, p<0.001) and differences in comedication were found. The stepwise logistic regression analysis retained high doses of IVIg (OR 3.03; CI 95%: 1.49-5.67) and diuretics therapy (OR 1.69; CI 95%: 1.06-3.97) when combined with the usual comorbid confounders.
  
  
  CONCLUSIONS
  The incidence of TEE from IVIg therapy remains high at one in six patients treated. The most remediable factor is a high daily IVIg load. Decreasing the daily IVIg dose together with carefully weighing diuretics therapy and comorbid risk factors may be the keys to saving lives.
authors.affiliation: Department of Clinical Pharmacology, Hospital Universitario La Paz, IdiPAZ, School of Medicine, Universidad Autónoma de Madrid, Madrid, Spain. Electronic address: elena.ramirez@inv.uam.es.
authors.forename: Elena
authors.initials: E
authors.lastname: Ramírez
authors.affiliation: Department of Pharmacy, Hospital Universitario La Paz, IdiPAZ, Madrid, Spain.
authors.forename: José A
authors.initials: JA
authors.lastname: Romero-Garrido
authors.affiliation: Department of Immunology, Hospital Universitario La Paz, IdiPAZ, Madrid, Spain.
authors.forename: Eduardo
authors.initials: E
authors.lastname: López-Granados
authors.affiliation: Department of Clinical Pharmacology, Hospital Universitario La Paz, IdiPAZ, School of Medicine, Universidad Autónoma de Madrid, Madrid, Spain.
authors.forename: Alberto M
authors.initials: AM
authors.lastname: Borobia
authors.affiliation: Department of Pharmacy, Hospital Universitario La Paz, IdiPAZ, Madrid, Spain.
authors.forename: Tamara
authors.initials: T
authors.lastname: Pérez
authors.affiliation: Department of Clinical Pharmacology, Hospital Universitario La Paz, IdiPAZ, School of Medicine, Universidad Autónoma de Madrid, Madrid, Spain.
authors.forename: Nicolás
authors.initials: N
authors.lastname: Medrano
authors.affiliation: Department of Pharmacy, Hospital Universitario La Paz, IdiPAZ, Madrid, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Rueda
authors.affiliation: Department of Clinical Pharmacology, Hospital Universitario La Paz, IdiPAZ, School of Medicine, Universidad Autónoma de Madrid, Madrid, Spain.
authors.forename: Hoi Y
authors.initials: HY
authors.lastname: Tong
authors.affiliation: Department of Pharmacy, Hospital Universitario La Paz, IdiPAZ, Madrid, Spain.
authors.forename: Alicia
authors.initials: A
authors.lastname: Herrero
authors.affiliation: Department of Clinical Pharmacology, Hospital Universitario La Paz, IdiPAZ, School of Medicine, Universidad Autónoma de Madrid, Madrid, Spain. Electronic address: jesus.frias@uam.es.
authors.forename: Jesús
authors.initials: J
authors.lastname: Frías
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D015897:Comorbidity; D005260:Female; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000008:administration & dosage* / Q000009:adverse effects*; D015994:Incidence; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D013923:Thromboembolism / Q000139:chemically induced*; D055815:Young Adult
chemical_list: D016756:Immunoglobulins, Intravenous
keywords: Comorbidity; Immunoglobulin therapy; Incidence studies; Pharmacoepidemiology; Thromboembolism