title: Hyperimmune globulins and same-day thrombotic adverse events as recorded in a large healthcare database during 2008-2011.
abstract: Thrombotic events (TEs) are rare serious complications following administration of hyperimmune globulin (HIG) products. Our retrospective claims-based study assessed occurrence of same-day TEs following administration of HIGs during 2008-2011 and examined potential risk factors using HealthCore's Integrated Research Database (HIRD(SM) ) and laboratory testing of products' procoagulant Factor XIa activity by U.S. Food and Drug Administration. Multivariable regression was used to estimate same-day TE risk for different products. Of 101,956 individuals exposed to 23 different HIG product groups, 86 (0.84 per 1,000 persons) had a TE diagnosis code (DC) recorded on the same day as HIG administration. Unadjusted same-day TE DC rates (per 1,000 persons) ranged from 0.4 to 148.9 for different products. GamaSTAN S/D IG >10 cc had statistically significantly higher same-day TE DC risk compared to Tetanus IG (OR = 57.57; 95% CI = 19.72-168.10). Increased TE risk was also observed with older age (≥45 years), prior thrombotic events, and hypercoagulable state(s). Laboratory investigation identified elevated Factor XIa activity for GamaSTAN S/D, HepaGam B, HyperHep B S/D, WinRho SDF, HyperRHO S/D full dose, and HyperTET S/D. Our study, for the first time, identified increase in the same-day TE DC risk with GamaSTAN S/D IG >10 cc and suggests potentially elevated TE risk with other HIGs.
authors.affiliation: Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, Rockville, Maryland.
authors.forename: Mikhail
authors.initials: M
authors.lastname: Menis
authors.forename: Gayathri
authors.initials: G
authors.lastname: Sridhar
authors.forename: Nandini
authors.initials: N
authors.lastname: Selvam
authors.forename: Mikhail V
authors.initials: MV
authors.lastname: Ovanesov
authors.forename: Hozefa A
authors.initials: HA
authors.lastname: Divan
authors.forename: Yideng
authors.initials: Y
authors.lastname: Liang
authors.forename: Dorothy
authors.initials: D
authors.lastname: Scott
authors.forename: Basil
authors.initials: B
authors.lastname: Golding
authors.forename: Richard
authors.initials: R
authors.lastname: Forshee
authors.forename: Robert
authors.initials: R
authors.lastname: Ball
authors.forename: Steven A
authors.initials: SA
authors.lastname: Anderson
authors.forename: Hector S
authors.initials: HS
authors.lastname: Izurieta
mesh_terms: D000328:Adult; D000367:Age Factors; D001780:Blood Coagulation Tests; D054598:Blue Cross Blue Shield Insurance Plans / Q000706:statistics & numerical data; D015986:Confounding Factors, Epidemiologic; D016208:Databases, Factual / Q000706:statistics & numerical data*; D004617:Embolism / Q000453:epidemiology / Q000209:etiology*; D015945:Factor XIa / Q000032:analysis; D005260:Female; D006801:Humans; D007136:Immunoglobulins / Q000009:adverse effects* / Q000737:chemistry; D016756:Immunoglobulins, Intravenous / Q000009:adverse effects / Q000737:chemistry; D008297:Male; D012008:Recurrence; D012189:Retrospective Studies; D012307:Risk Factors; D013917:Thrombin / Q000096:biosynthesis; D019851:Thrombophilia / Q000150:complications; D013927:Thrombosis / Q000453:epidemiology / Q000209:etiology*; D013997:Time Factors; D014481:United States / Q000453:epidemiology
chemical_list: D007136:Immunoglobulins; D016756:Immunoglobulins, Intravenous; D015945:Factor XIa; D013917:Thrombin