Joint Health Command, Australian Defence Force, Canberra, Australian Capital Territory, Australia.
University of Queensland, Brisbane, Queensland, Australia.
Transfusion. 2019 Sep;59(9):2794-2804. doi: 10.1111/trf.15423. Epub 2019 Jul 10.
Cryopreservation extends platelet (PLT) shelf life from 5 to 7 days to 2 to 4 years. However, only 73 patients have been transfused cryopreserved PLTs in published randomized controlled trials (RCTs), making safety data insufficient for regulatory approval.
The Cryopreserved vs. Liquid Platelet (CLIP) study was a double-blind, pilot, multicenter RCT involving high-risk cardiothoracic surgical patients in four Australian hospitals. The objective was to test, as the primary outcome, the feasibility and safety of the protocol. Patients were allocated to study group by permuted block randomization, with patients and clinicians blinded by use of an opaque shroud placed over each study PLT unit. Up to 3 units of cryopreserved or liquid-stored PLTs were administered per patient. No other aspect of patient care was affected. Adverse events were actively sought.
A total of 121 patients were randomized, of whom 23 received cryopreserved PLTs and 18 received liquid-stored PLTs. There were no differences in blood loss (median, 715 mL vs. 805 mL at 24 hr; difference between groups 90 mL [95% CI, -343.8 to 163.8 mL], p = 0.41), but the Bleeding Academic Research Consortium criterion for significant postoperative hemorrhage in cardiac surgery composite bleeding endpoint occurred in nearly twice as many patients in the liquid-stored group (55.6% vs. 30.4%, p = 0.10). Red blood cell transfusion requirements were a median of 3 units in the cryopreserved group versus 4 units with liquid-stored PLTs (difference between groups, 1 unit [95% CI, -3.1 to 1.1 units]; p = 0.23). Patients in the cryopreserved group were more likely to be transfused fresh-frozen plasma (78.3% vs. 27.8%, p = 0.002) and received more study PLT units (median, 2 units vs. 1 unit; difference between groups, 1 unit [95% CI, -0.03 to 2.0 units]; p = 0.012). There were no between-group differences in potential harms including deep venous thrombosis, myocardial infarction, respiratory function, infection, and renal function. No patient had died at 28 days, and postoperative length of stay was similar in each group.
In this pilot RCT, compared to liquid-stored PLTs, cryopreserved PLTs were associated with no evidence of harm. A definitive study testing safety and hemostatic effectiveness is warranted.
血小板（PLT）的冷冻保存将其保存期从 5 至 7 天延长至 2 至 4 年。然而，只有 73 名患者在已发表的随机对照试验（RCT）中接受了冷冻保存的 PLT 输注，这使得安全性数据不足以获得监管部门的批准。
冷冻保存与液体血小板（CLIP）研究是一项在澳大利亚四家医院进行的高风险心胸外科患者的双盲、试点、多中心 RCT。主要目的是检测方案的可行性和安全性。采用区组随机化分配患者，使用覆盖每个研究 PLT 单位的不透明罩对患者和临床医生进行盲法。每个患者最多可接受 3 单位的冷冻或液体储存 PLT。不影响患者护理的其他方面。积极寻找不良事件。
共有 121 名患者被随机分配，其中 23 名患者接受冷冻保存的 PLT，18 名患者接受液体储存的 PLT。24 小时时血液丢失无差异（中位数，715ml 与 805ml；两组间差值为 90ml [95%CI，-343.8 至 163.8ml]，p=0.41），但心脏手术复合出血终点的术后出血学术研究联合会（BARC）标准表明，液体储存组发生显著术后出血的患者比例几乎是冷冻保存组的两倍（55.6%比 30.4%，p=0.10）。冷冻保存组的红细胞输血需求中位数为 3 单位，而液体储存 PLT 组为 4 单位（两组间差值，1 单位 [95%CI，-3.1 至 1.1 单位]；p=0.23）。冷冻保存组更有可能输注新鲜冷冻血浆（78.3%比 27.8%，p=0.002），并且接受了更多的研究 PLT 单位（中位数，2 单位比 1 单位；两组间差值，1 单位 [95%CI，-0.03 至 2.0 单位]；p=0.012）。两组之间在潜在危害方面无差异，包括深静脉血栓形成、心肌梗死、呼吸功能、感染和肾功能。两组在 28 天时均无患者死亡，术后住院时间相似。
在这项试点 RCT 中，与液体储存 PLT 相比，冷冻保存 PLT 未显示出任何危害的证据。有必要进行一项测试安全性和止血效果的确定性研究。
