Scientific Publications by FDA Staff

J Thromb Haemost 2015 Dec;13(12):2168-79

Clotting factor product administration and same-day occurrence of thrombotic events, as recorded in large healthcare database during 2008-2013.

Ekezue BF, Sridhar G, Ovanesov MV, Forshee RA, Izurieta HS, Selvam N, Parunov L, Jain N, Mintz PD, Epstein J, Anderson SA, Menis M

BACKGROUND: Thrombotic events (TEs) are serious adverse events that can occur following administration of clotting factors (CFs). OBJECTIVES: 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 large commercial insurance database. CF products were identified by procedure codes, and TEs were ascertained via diagnosis codes. Crude same-day TE rates (per 1,000 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 procoagulant activities of FIX products. RESULTS: Of 3,801 individuals exposed to CFs, 117 (30.8 per 1,000) had same-day TEs recorded. Crude same-day TE rate was higher for CF users without CFD, 70.2 (102 of 1,452), as compared to those with CFD, 6.4 (15 of 2,349), RR=11.0, 95% CI 6.4-18.9. For individuals without CFD, 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 to fibrin sealant. Increased TE risk was found with older age (=45 years), history of TEs, and underlying health conditions. Laboratory identified elevated procoagulant activity in Profilnine® and Benefix® . CONCLUSIONS: Study shows increased same-day TE risk for CF users without CFD and suggests substantial off-label CF use. Study findings also show elevated same-day TE rates for different CF products and suggest importance of product properties and patient factors.