Department of Anesthesiology and Perioperative Medicine, Drexel University College of Medicine, Philadelphia, PA 19102, USA.
Thromb Res. 2012 Jun;129(6):793-6. doi: 10.1016/j.thromres.2011.08.005. Epub 2011 Aug 26.
Fibrinogen concentrate has been demonstrated to enhance coagulation in vitro and in several clinical settings of coagulopathy. We have recently demonstrated that carbon monoxide releasing molecule-2 (tricarbonyldichlororuthenium (II) dimer; CORM-2) enhances fibrinogen as a substrate for thrombin via an attached heme. The objective of this study was to determine if CORM-2 modified fibrinogen concentrate would enhance coagulation more effectively than CORM-2 naïve fibrinogen concentrate.
In the first series of experiments, fibrinogen concentrate (final concentration 300mg/dl) was exposed to 0, 50 or 100μM CORM-2 for 5min at 37°C prior to being added to citrated, fibrinogen depleted plasma. In another series of experiments, citrated plasma obtained from 12 normal subjects was 50% diluted with crystalloid to which was added fibrinogen concentrate (final concentration 300mg/dl) exposed to 0 or 100μM CORM-2. Coagulation was activated with tissue factor (n=8 per condition). Thrombus growth was monitored with thrombelastography for 15min.
CORM-2 modification of fibrinogen concentrate significantly enhanced the velocity of clot formation (30-50%) and strength (15-31%) in fibrinogen deficient plasma. Similarly, while diluted plasma-derived thrombi demonstrated a marked decrease in velocity of formation (54%) and strength (61%), fibrinogen concentrate significantly enhanced velocity (217%) and strength (171%); however, CORM-2 modified fibrinogen concentrate significantly increased velocity (303%) and strength (205%) to a greater extent. Additional in vitro investigation and in vivo preclinical assessments of the hemostatic efficacy of CORM-2 modified fibrinogen concentrate are warranted.
纤维蛋白原浓缩物已被证明可增强体外和几种凝血功能障碍临床情况下的凝血。我们最近证明，一氧化碳释放分子-2（三羰基二氯合钌（II）二聚体；CORM-2）通过附着的血红素增强纤维蛋白原作为凝血酶的底物。本研究的目的是确定 CORM-2 修饰的纤维蛋白原浓缩物是否比 CORM-2 原始纤维蛋白原浓缩物更有效地增强凝血。
在一系列实验中，纤维蛋白原浓缩物（最终浓度为 300mg/dl）在 37°C 下暴露于 0、50 或 100μM CORM-2 5min，然后加入柠檬酸化的、纤维蛋白原耗尽的血浆中。在另一系列实验中，从 12 名正常受试者获得的柠檬酸化血浆用晶体稀释 50%，加入纤维蛋白原浓缩物（最终浓度为 300mg/dl），暴露于 0 或 100μM CORM-2。用组织因子激活凝血（n=8 个条件）。用血栓弹性描记术监测血栓形成 15min。
纤维蛋白原浓缩物的 CORM-2 修饰显著增强了纤维蛋白原缺乏血浆中的血凝块形成速度（30-50%）和强度（15-31%）。同样，虽然稀释的血浆衍生血栓形成速度明显下降（54%）和强度（61%），纤维蛋白原浓缩物显著增强速度（217%）和强度（171%）；然而，CORM-2 修饰的纤维蛋白原浓缩物以更大的程度显著增加速度（303%）和强度（205%）。需要进一步的体外研究和体内临床前评估 CORM-2 修饰的纤维蛋白原浓缩物的止血功效。
