HealthCore Inc, Silver Spring, MD, USA.
Center for Biologics Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, USA.
J Thromb Haemost. 2015 Dec;13(12):2168-79. doi: 10.1111/jth.13155. Epub 2015 Nov 25.
Thrombotic events (TEs) are serious adverse events that can occur following administration of clotting factors (CFs).
To evaluate occurrence of same-day TEs for different CF products and potential risk factors.
A retrospective cohort study of individuals exposed to CF products during 2008-2013 was conducted using a large commercial insurance database. CF products were identified by procedure codes, and TEs were ascertained via diagnosis codes. Crude same-day TE rates (per 1000 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 the procoagulant activities of FIX products.
Of 3801 individuals exposed to CFs, 117 (30.8 per 1000) had same-day TEs recorded. The crude same-day TE rate was higher for CF users without CFD, 70.2 (102 of 1452), as compared with those with CFD, 6.4 (15 of 2349) (RR, 11.0; 95% CI, 6.4-18.9). For individuals without CFD, a 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 with fibrin sealant. An increased risk of a TE was found with older age (≥ 45 years), history of TEs and underlying health conditions. The laboratory identified elevated procoagulant activity in Profilnine(®) and Benefix(®) .
The study shows an increased same-day TE risk for CF users without CFD and suggests substantial off-label CF use. The study findings also show elevated same-day TE rates for different CF products and suggest the importance of product properties and patient factors.
血栓事件（TEs）是在给予凝血因子（CFs）后可能发生的严重不良事件。
评估不同 CF 产品的同日 TE 发生情况和潜在的危险因素。
使用大型商业保险数据库，对 2008-2013 年接受 CF 产品治疗的个体进行了一项回顾性队列研究。CF 产品通过手术代码识别，TE 通过诊断代码确定。总体和按先天性因子缺乏症（CFD）状态、CF 产品、年龄和性别分别估计了同日 TE 发生率（每 1000 名暴露者中的发生率）。多变量逻辑回归分析用于控制混杂因素。实验室分析用于比较 FIX 产品的促凝活性。
在 3801 名接受 CF 治疗的个体中，有 117 名（30.8/1000）记录到同日 TE。无 CFD 的 CF 使用者的同日 TE 发生率较高，为 70.2（1452 例中的 102 例），而有 CFD 的 CF 使用者为 6.4（2349 例中的 15 例）（RR，11.0；95%CI，6.4-18.9）。对于无 CFD 的个体，与纤维蛋白密封剂相比，因子 IX 复合物（OR，6.92；95%CI，3.11-15.40）、因子 VIIa（OR，9.42；95%CI，4.99-17.78）和其他产品的同日 TE 风险显著增加。年龄较大（≥45 岁）、有 TE 病史和潜在健康状况与 TE 风险增加有关。实验室发现 Profilnine(®)和 Benefix(®)的促凝活性升高。
该研究显示无 CFD 的 CF 使用者的同日 TE 风险增加，并表明 CF 的大量非适应证使用。研究结果还显示不同 CF 产品的同日 TE 发生率较高，提示产品特性和患者因素的重要性。
