Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, Rockville, Maryland.
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.
血栓事件（TEs）是在使用高免疫球蛋白（HIG）产品后罕见的严重并发症。我们的回顾性基于索赔的研究评估了在 2008 年至 2011 年期间使用 HIG 后当天发生的 TEs 的发生情况，并使用 HealthCore 的综合研究数据库（HIRD（SM））和美国食品和药物管理局对产品促凝血因子 XIa 活性的实验室检测来检查潜在的危险因素。多变量回归用于估计不同产品的当天 TE 风险。在暴露于 23 种不同 HIG 产品组的 101956 人中，有 86 人（每 1000 人中有 0.84 人）在接受 HIG 治疗的同一天记录了 TE 诊断代码（DC）。不同产品的未经调整的当天 TE DC 率（每 1000 人）范围为 0.4 至 148.9。与破伤风免疫球蛋白相比，GamaSTAN S/D IG>10 cc 的同一天 TE DC 风险具有统计学显著升高（OR=57.57；95%CI=19.72-168.10）。观察到年龄较大（≥45 岁）、先前存在血栓事件和高凝状态与 TE 风险增加有关。实验室研究发现 GamaSTAN S/D、HepaGam B、HyperHep B S/D、WinRho SDF、HyperRHO S/D 全剂量和 HyperTET S/D 的因子 XIa 活性升高。我们的研究首次确定了 GamaSTAN S/D IG>10 cc 与同一天 TE DC 风险增加之间的关系，并表明其他 HIG 可能具有潜在升高的 TE 风险。
