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 5 57.57; 95% CI 5 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. Am.

Adverse effects of immunoglobulin G therapy: thromboembolism and haemolysis

“…Variances in rates of TAEs between different IgG products were also noted, with an approximately three‐fold variation overall. The extension of the retrospective study (2008–11) looked at hyperimmune globulin products; the overall rate of TAEs was reported at one‐tenth of that in the initial study (< 0·01%); however, the highest rates were very similar to those observed previously .…”

Intravenous immune globulin and thromboembolic adverse events in patients with hematologic malignancy

“…13,14,[24][25][26][27][28][29][30][31][32] However, the extent to which these events are attributable to the IVIg itself rather than other risk factors is unclear, as is the risk associated with low doses of IVIg for immunodeficiency. In this retrospective cohort study, we assessed rates of clinically serious arterial and venous TEEs in older patients with CLL or MM who initiated IVIg therapy.…”

Synergy Between Tissue Factor and Exogenous Factor XIa in Initiating Coagulation

“…Studies showed that some off- the-shelf IGIV products were able to generate thrombin and that these same products were contaminated with FXIa [17]. More recent studies found FXIa in batches of IGIV shown to be thrombotic [17, 18] and others, although not based on thrombotic batches, also found an association of FXIa with IGIV products [19, 20, 21, 22]. Another line of evidence is the thrombogenicity of FXI concentrates used to treat FXI deficient patients.…”