From the Shock Trauma Center (A.Z., F.W., S.C., R.A.K.), University of Maryland School of Medicine, Baltimore, Maryland; Cerus Corporation (L.C.), Concord; Department of Laboratory Medicine, University of California (S.P.), San Francisco, San Francisco, California.
J Trauma Acute Care Surg. 2023 Oct 1;95(4):529-534. doi: 10.1097/TA.0000000000003981. Epub 2023 Jun 14.
Cryoprecipitate (CP) can augment hemostasis after hemorrhagic shock (HS). Similar to fresh frozen plasma (FFP), CP may provide short-term endothelial protection. We tested a new 5-day postthaw CP (5-day pathogen-reduced cryoprecipitate [5PRC]) and lyophilized pathogen-reduced cryoprecipitate (LPRC) to overcome challenges of early administration and hypothesized that 5PRC and LPRC would provide lasting organ protection in a rodent model of HS.
Mice underwent trauma/HS (laparotomy then HS), mean arterial pressure (MAP) 35 × 90 minutes, and then 6 hours of hypotensive resuscitation (MAP, 55-60 mm Hg) with lactated Ringer's solution (LR), FFP, CP, 5PRC, or LPRC and compared with shams. Animals were followed for 72 hours. Organs and blood were collected. Data are presented as mean ± SD and analysis of variance with Bonferroni post hoc.
Mean arterial pressure was comparable between experimental groups at baseline, preresuscitation, and 6 hours per protocol. However, volume needed to resuscitate to target MAP over 6 hours was less than half for CP, 5PRC, LPRC, and FFP compared with LR, suggesting that CP products can serve as effective resuscitative agents. Mean arterial pressure at 72 hours was also significantly higher in the CP, 5PRC, and FFP groups compared with LR. Resuscitation with CP, 5PRC, and LPRC provided lasting protection from gut injury and enhanced syndecan immunostaining comparable with FFP, while LR mice demonstrated persistent organ dysfunction. Sustained endothelial protection was demonstrated by lessened lung permeability, while cystatin C was an indicator of kidney function, and liver aspartate aminotransferase and alanine transaminase returned to sham levels in all groups.
Cryoprecipitate products can provide lasting organ protection comparable with FFP in a sustained rodent model of trauma/HS and hypotensive resuscitation. The availability of 5PRC and LPRC will allow for investigation into the immediate use of cryoprecipitate for severely injured patients. As lyophilized products such as cryoprecipitate become available clinically, their use has important implications for prehospital, rural, and battlefield usage.
冷沉淀（CP）可在出血性休克（HS）后增强止血作用。类似于新鲜冷冻血浆（FFP），CP 可能提供短期内皮保护。我们测试了一种新的 5 天解冻 CP（5 天减病原体冷沉淀[5PRC]）和冻干减病原体冷沉淀（LPRC），以克服早期给药的挑战，并假设 5PRC 和 LPRC 将在 HS 的啮齿动物模型中提供持久的器官保护。
小鼠接受创伤/HS（剖腹术然后 HS），平均动脉压（MAP）35×90 分钟，然后进行 6 小时低血压复苏（MAP，55-60mmHg）用乳酸林格氏液（LR）、FFP、CP、5PRC 或 LPRC 与假手术组进行比较。动物随访 72 小时。采集器官和血液。数据以均值±SD 表示，并进行方差分析和 Bonferroni 事后检验。
实验各组在基线、预复苏和 6 小时内的平均动脉压在方案中均无差异。然而，CP、5PRC、LPRC 和 FFP 组在 6 小时内达到目标 MAP 所需的复苏体积不到 LR 组的一半，表明 CP 产品可用作有效的复苏剂。72 小时时 CP、5PRC 和 FFP 组的平均动脉压也明显高于 LR 组。CP、5PRC 和 LPRC 的复苏提供了从肠道损伤中持续的保护，并增强了与 FFP 相当的 syndecan 免疫染色，而 LR 组的小鼠则表现出持续的器官功能障碍。通过减少肺通透性来维持内皮保护，而半胱氨酸蛋白酶抑制剂 C 是肾功能的指标，肝天门冬氨酸氨基转移酶和丙氨酸氨基转移酶在所有组中均恢复到假手术水平。
CP 产品可在持续的创伤/HS 和低血压复苏的啮齿动物模型中提供与 FFP 相当的持久器官保护。5PRC 和 LPRC 的可用性将允许对严重受伤患者立即使用冷沉淀进行研究。随着冻干产品（如冷沉淀）在临床上的应用，它们的使用对院前、农村和战场的使用具有重要意义。
