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来自多国 Glanzmann's 血小板无力症注册研究的独立裁判评估血小板反应性和 rFVIIa 在出血发作和手术中的疗效。

Independent adjudicator assessments of platelet refractoriness and rFVIIa efficacy in bleeding episodes and surgeries from the multinational Glanzmann's thrombasthenia registry.

机构信息

Oregon Health & Science University, Portland, Oregon, USA.

Children's Hospital of Michigan, Wayne State University, Detroit, Michigan, USA.

出版信息

Am J Hematol. 2017 Jul;92(7):646-652. doi: 10.1002/ajh.24741. Epub 2017 May 9.

Abstract

Glanzmann's thrombasthenia (GT) is a rare congenital bleeding disorder associated with decreased platelet aggregation due to qualitative/quantitative deficiencies of the fibrinogen receptor. Severe bleeding episodes and perioperative bleeding are typically managed with platelet transfusions, although patients can develop anti-platelet antibodies or experience clinical refractoriness. The GT Registry (GTR) was established to collect efficacy/safety data on hemostatic treatments for GT, including recombinant factor VIIa (rFVIIa). At the request of the United States Food and Drug Administration, three hematology experts evaluated platelet refractoriness, antibody status, and rFVIIa efficacy data on a case-by-case basis to support a potential indication for rFVIIa in GT. Adjudication included 195 patients with 810 events (619 severe bleeding episodes, 192 surgeries), and a consensus algorithm was developed to describe adjudicators' coding of refractoriness and antibody status based on treatment patterns over time. Most rFVIIa-treated events were in patients without refractoriness or antibodies. Adjudicators rated most rFVIIa-treated bleeding episodes as successful (251/266, 94.4%; rFVIIa only, 101/109, 92.7%; rFVIIa ± platelets ± other agents, 150/157, 95.5%); efficacy was consistent in patients with platelet refractoriness ± antibodies (75/79, 94.9%), antibodies only (10/10, 100.0%), and neither/unknown (166/177, 93.8%). Adjudicators also rated most rFVIIa-treated surgeries as successful (159/160, 99.4%; rFVIIa only, 65/66, 98.5%; rFVIIa ± platelets ± other agents, 94/94, 100.0%); efficacy was consistent in patients with platelet refractoriness ± antibodies (69/70, 98.6%), antibodies only (24/24, 100.0%), and neither/unknown (66/66, 100.0%). Unblinding the adjudicators to investigator efficacy ratings changed few assessments. Doses of rFVIIa were narrowly distributed, regardless of other hemostatic agents used.

摘要

血小板无力症(GT)是一种罕见的先天性出血性疾病,由于纤维蛋白原受体的质量/数量缺陷,导致血小板聚集减少。严重出血发作和围手术期出血通常采用血小板输注治疗,尽管患者可能会产生抗血小板抗体或出现临床抵抗。GT 登记处(GTR)的建立是为了收集止血治疗 GT 的疗效/安全性数据,包括重组因子 VIIa(rFVIIa)。应美国食品和药物管理局的要求,三位血液学专家对血小板抵抗、抗体状态和 rFVIIa 的疗效数据进行了逐案评估,以支持 rFVIIa 在 GT 中的潜在适应证。裁决包括 195 名患者的 810 项事件(619 例严重出血发作,192 例手术),并制定了一个共识算法,根据随时间推移的治疗模式来描述裁决者对抵抗和抗体状态的编码。大多数接受 rFVIIa 治疗的事件发生在无抵抗或无抗体的患者中。裁决者对大多数接受 rFVIIa 治疗的出血发作进行了成功评分(251/266,94.4%;仅 rFVIIa,101/109,92.7%;rFVIIa ± 血小板 ± 其他药物,150/157,95.5%);在血小板抵抗 ± 抗体(75/79,94.9%)、仅抗体(10/10,100.0%)和既无/未知(166/177,93.8%)的患者中,疗效一致。裁决者还对大多数接受 rFVIIa 治疗的手术进行了成功评分(159/160,99.4%;仅 rFVIIa,65/66,98.5%;rFVIIa ± 血小板 ± 其他药物,94/94,100.0%);在血小板抵抗 ± 抗体(69/70,98.6%)、仅抗体(24/24,100.0%)和既无/未知(66/66,100.0%)的患者中,疗效一致。对裁决者进行盲法评估以改变他们对研究者疗效评分的看法的情况很少。rFVIIa 的剂量分布狭窄,无论是否使用其他止血药物。

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