title: Clotting factor product administration and same-day occurrence of thrombotic events, as recorded in a large healthcare database during 2008-2013.
abstract: BACKGROUND
  Thrombotic events (TEs) are serious adverse events that can occur following administration of clotting factors (CFs).
  
  
  OBJECTIVE
  To evaluate occurrence of same-day TEs for different CF products and potential risk factors.
  
  
  METHODS
  A retrospective cohort study of individuals exposed to CF products during 2008-2013 was conducted using a large commercial insurance database. CF products were identified by procedure codes, and TEs were ascertained via diagnosis codes. Crude same-day TE rates (per 1000 persons exposed) were estimated overall and by congenital factor deficiency (CFD) status, CF products, age and gender. Multivariable logistic regression analyses were used to control for confounding. Laboratory analysis was used to compare the procoagulant activities of FIX products.
  
  
  RESULTS
  Of 3801 individuals exposed to CFs, 117 (30.8 per 1000) had same-day TEs recorded. The crude same-day TE rate was higher for CF users without CFD, 70.2 (102 of 1452), as compared with those with CFD, 6.4 (15 of 2349) (RR, 11.0; 95% CI, 6.4-18.9). For individuals without CFD, a significantly increased same-day TE risk was identified for factor IX complex (OR, 6.92; 95% CI, 3.11-15.40), factor VIIa (OR, 9.42; 95% CI, 4.99-17.78) and other products when compared with fibrin sealant. An increased risk of a TE was found with older age (≥ 45 years), history of TEs and underlying health conditions. The laboratory identified elevated procoagulant activity in Profilnine(®) and Benefix(®) .
  
  
  CONCLUSIONS
  The study shows an increased same-day TE risk for CF users without CFD and suggests substantial off-label CF use. The study findings also show elevated same-day TE rates for different CF products and suggest the importance of product properties and patient factors.
authors.affiliation: HealthCore Inc, Silver Spring, MD, USA.
authors.forename: B F
authors.initials: BF
authors.lastname: Ekezue
authors.affiliation: HealthCore Inc, Silver Spring, MD, USA.
authors.forename: G
authors.initials: G
authors.lastname: Sridhar
authors.affiliation: Center for Biologics Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, USA.
authors.forename: M V
authors.initials: MV
authors.lastname: Ovanesov
authors.affiliation: Center for Biologics Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, USA.
authors.forename: R A
authors.initials: RA
authors.lastname: Forshee
authors.affiliation: Center for Biologics Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, USA.
authors.forename: H S
authors.initials: HS
authors.lastname: Izurieta
authors.affiliation: HealthCore Inc, Silver Spring, MD, USA.
authors.forename: N
authors.initials: N
authors.lastname: Selvam
authors.affiliation: Center for Biologics Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, USA.
authors.forename: L A
authors.initials: LA
authors.lastname: Parunov
authors.affiliation: Center for Biologics Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, USA.
authors.forename: N
authors.initials: N
authors.lastname: Jain
authors.affiliation: Center for Biologics Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, USA.
authors.forename: P D
authors.initials: PD
authors.lastname: Mintz
authors.affiliation: Center for Biologics Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, USA.
authors.forename: J S
authors.initials: JS
authors.lastname: Epstein
authors.affiliation: Center for Biologics Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, USA.
authors.forename: S A
authors.initials: SA
authors.lastname: Anderson
authors.affiliation: Center for Biologics Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, USA.
authors.forename: M D
authors.initials: MD
authors.lastname: Menis
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D016009:Chi-Square Distribution; D003029:Coagulants / Q000008:administration & dosage / Q000009:adverse effects*; D015897:Comorbidity; D016208:Databases, Factual; D004334:Drug Administration Schedule; D004340:Drug Contamination; D005164:Factor IX / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D056687:Off-Label Use; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D013927:Thrombosis / Q000139:chemically induced* / Q000175:diagnosis / Q000453:epidemiology; D013997:Time Factors; D014481:United States / Q000453:epidemiology; D055815:Young Adult
chemical_list: D003029:Coagulants; D005164:Factor IX
keywords: clotting factors; healthcare; laboratory; risk factors; thrombosis