Goodnough Lawrence Tim, Levy Jerrold H
Department of Pathology and Medicine, Stanford University, Stanford, California.
Department of Anesthesiology and Critical Care, Duke University, Durham, North Carolina.
Semin Thromb Hemost. 2016 Mar;42(2):125-32. doi: 10.1055/s-0035-1569068. Epub 2016 Feb 2.
Recombinant activated factor VIIa (rFVIIa) is a prohemostatic agent initially approved for use in hemophilia patients with inhibitors and recently for Glanzmann thrombasthenia. Despite its approval indications, rFVIIa has also been used for a diverse range of off-label indications to treat bleeding related to traumatic injury, major hemorrhage following surgery, intracranial hemorrhage, and for uncontrolled bleeding as a prothrombotic hemostatic agent. Despite its off-label use, the benefit of rFVIIa in most nonhemophilia settings remains uncertain as the majority of clinical trials have not consistently demonstrated beneficial effects as determined by reduced bleeding, decreased blood product utilization, or have not demonstrated a mortality benefit. As with any prohemostatic agent, the risk of thromboembolic events is increased when rFVIIa is used off-label. Pooled data from randomized nonhemophilia studies report an increased risk in the elderly for arterial thromboses, although most individual trials have been underpowered to determine adverse thrombotic events. The causes of thrombotic adverse events associated with off-label use of rFVIIa may be due to an increased risk of adverse events due to critical illness or due to higher doses of rFVIIa used in off-label trials. Without clearly supportive data, physicians should consider risk versus benefit and exercise restraint using rFVIIa in off-label settings. Further, evidence-based guidelines should be developed by professional organizations, and additional randomized controlled clinical trials are needed to further assess the efficacy and safety of off-label rFVIIa use.
重组活化因子VIIa（rFVIIa）是一种促止血药物，最初被批准用于有抑制物的血友病患者，最近也被批准用于治疗血小板无力症。尽管有批准的适应症，但rFVIIa也被用于多种非适应症的情况，以治疗与创伤性损伤相关的出血、手术后的大出血、颅内出血，以及作为促血栓形成的止血剂用于控制出血。尽管其使用属于非适应症范围，但rFVIIa在大多数非血友病情况下的益处仍不确定，因为大多数临床试验并未始终如一地证明其有益效果，如通过减少出血、降低血液制品使用率来确定，或者未证明其有死亡率益处。与任何促止血药物一样，rFVIIa非适应症使用时血栓栓塞事件的风险会增加。来自非血友病随机研究的汇总数据报告称，老年人发生动脉血栓形成的风险增加，尽管大多数个别试验的样本量不足以确定不良血栓事件。与rFVIIa非适应症使用相关的血栓形成不良事件的原因可能是由于危重病导致不良事件风险增加，或者是由于非适应症试验中使用了更高剂量的rFVIIa。在没有明确支持性数据的情况下，医生应权衡风险与益处，并在非适应症情况下谨慎使用rFVIIa。此外，专业组织应制定基于证据的指南，还需要更多的随机对照临床试验来进一步评估rFVIIa非适应症使用的疗效和安全性。
