Kheirabadi Bijan S, Mace James E, Terrazas Irasema B, Fedyk Chriselda G, Estep J Scot, Dubick Michael A, Blackbourne Lorne H
US Army Institute of Surgical Research, Ft. Sam Houston, Texas, USA.
J Trauma. 2010 Feb;68(2):269-78. doi: 10.1097/TA.0b013e3181c97ef1.
In 2007, a potent procoagulant mineral called WoundStat (WS), consisting of smectite granules, received clearance from the Food and Drug Administration for marketing in the United States for temporary treatment of external hemorrhage. Previously, we found that microscopic WS particles remained in the injured vessels that were treated, despite seemingly adequate wound debridement. Thus, we investigated the thromboembolic risk of using WS when compared with kaolin-coated gauze, Combat Gauze (CG); or regular gauze, Kerlix (KX) to treat an external wound with vascular injuries in pigs.
The right common carotid artery and external jugular vein of pigs were isolated and sharply transected (50%). After 30 seconds of free bleeding, the neck wounds were packed with WS, CG, or KX and compressed until hemostasis was achieved (n = 8 per group). Wounds were debrided after 2 hours, and vascular injuries were primarily repaired with suture. Blood flow was restored after infusing 1 L of crystalloid (no heparin or aspirin) and the wounds were closed. Two hours later, computed tomographic angiography was performed, and the wounds were reopened to harvest the vessels. The brains and lungs were recovered for gross and microscopic examination after euthanasia.
No differences were found in baseline measurements. Thrombelastography showed similar hypercoagulability of the final blood samples when compared with baselines in all groups. All vessels treated with KX or CG were patent and had no thrombus or blood clot in their lumen. In contrast, seven of eight carotid arteries and six of eight jugular veins treated with WS developed large occlusive red thrombi and had no flow. Small clots and WS residues were also found in the lungs of two pigs. Histologically, significant endothelial and transmural damage was seen in WS-treated vessels with luminal thrombi and embedded WS residues.
WS granules caused endothelial injury and significant transmural damage to the vessels that render them nonviable for primary surgical repair. The granules can enter systemic circulation and cause distal thrombosis in vital organs. More relevant in vitro and in vivo safety tests should be required for clearance of new hemostatic agents.
2007年，一种名为创伤止血剂（WoundStat，WS）的强效促凝血矿物质，由蒙脱石颗粒组成，获得美国食品药品监督管理局批准在美国上市，用于临时治疗外出血。此前，我们发现尽管伤口清创看似充分，但微观层面的WS颗粒仍留在接受治疗的受伤血管中。因此，我们研究了与高岭土涂层纱布（战斗纱布，CG）或普通纱布（柯利克斯纱布，KX）相比，使用WS治疗猪的伴有血管损伤的外部伤口时的血栓栓塞风险。
分离猪的右颈总动脉和颈外静脉并锐性横断（50%）。自由出血30秒后，用WS、CG或KX填充颈部伤口并加压直至止血（每组n = 8）。2小时后进行伤口清创，血管损伤主要用缝线修复。输注1升晶体液（未使用肝素或阿司匹林）后恢复血流，然后闭合伤口。两小时后，进行计算机断层血管造影，重新打开伤口以获取血管。安乐死后取出大脑和肺进行大体和显微镜检查。
基线测量未发现差异。血栓弹力图显示，与所有组的基线相比，最终血样的高凝性相似。所有用KX或CG治疗的血管均通畅，管腔内无血栓或血凝块。相比之下，用WS治疗的8条颈动脉中有7条和8条颈静脉中有6条形成了大的闭塞性红色血栓且无血流。在2头猪的肺中也发现了小血栓和WS残留物。组织学上，在有管腔内血栓和嵌入的WS残留物的WS治疗血管中可见明显的内皮和透壁损伤。
WS颗粒导致血管内皮损伤和明显的透壁损伤，使其无法进行一期手术修复。这些颗粒可进入体循环并导致重要器官的远端血栓形成。新型止血剂的批准应要求进行更相关的体外和体内安全性测试。
