Hyperimmune globulins and same-day thrombotic adverse events as recorded in a large healthcare database during 2008-2011

Am J Hematol. 2013 Dec;88(12):1035-40. doi: 10.1002/ajh.23559. Epub 2013 Sep 12.


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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Age Factors
  • Blood Coagulation Tests
  • Blue Cross Blue Shield Insurance Plans / statistics & numerical data
  • Confounding Factors, Epidemiologic
  • Databases, Factual / statistics & numerical data*
  • Embolism / epidemiology
  • Embolism / etiology*
  • Factor XIa / analysis
  • Female
  • Humans
  • Immunoglobulins / adverse effects*
  • Immunoglobulins / chemistry
  • Immunoglobulins, Intravenous / adverse effects
  • Immunoglobulins, Intravenous / chemistry
  • Male
  • Recurrence
  • Retrospective Studies
  • Risk Factors
  • Thrombin / biosynthesis
  • Thrombophilia / complications
  • Thrombosis / epidemiology
  • Thrombosis / etiology*
  • Time Factors
  • United States / epidemiology


  • Immunoglobulins
  • Immunoglobulins, Intravenous
  • Factor XIa
  • Thrombin