Moallempour Mojgan, Jahr Jonathan S, Lim Jennifer C, Weeks David, Butch Anthony, Driessen Bernd
Department of Anesthesiology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
J Cardiothorac Vasc Anesth. 2009 Feb;23(1):41-7. doi: 10.1053/j.jvca.2008.06.006. Epub 2008 Aug 29.
Because oxidation affects platelet and coagulation factors, hemoglobin auto-oxidation in HBOCs results in the transformation to methemoglobin, which may have additive adverse effects on coagulation. The risk of coagulopathy after different dilutions of HBOC-200 with low and high methemoglobin concentrations was studied.
A laboratory study on donor blood using thromboelastography (TEG; Haemoscope, Niles, IL).
A university laboratory.
Volunteer donor blood.
Blood samples simulated hemodilution during clinical resuscitation of hemorrhagic shock with varying doses of HBOC-200 (Oxyglobin; Biopure Corp, Cambridge, MA). Coagulopathy related to 1:11, 1:5, 1:2, and 1:1 dilution of whole blood with HBOC-200 high methemoglobin concentrations (65%) and HBOC-200 low methemoglobin concentrations (1%) were analyzed.
Analysis of fixed effects of dilution on coagulation showed that the progressive dilution of HBOC-200 (low methemoglobin) and HBOC-200 (high methemoglobin) produced significant prolongation in reaction time (R) and clot propagation (K) and significant decreases in clot kinetics (alpha) and clot strength (MA and G). Analysis of fixed effects of treatment group on coagulation showed that clot propagation (K, alpha) and clot strength (MA and G) are significantly different in HBOC-200 (high methemoglobin) compared with HBOC-200 (low methemoglobin).
High methemoglobin concentrations in HBOC-200 cause additive coagulation impairment that likely results from the effects of oxidative substances on platelet function and coagulation proteins. Oxidative products adversely react with coagulation factors and modify redox-sensitive sites in the platelets. Therefore, if methemoglobinemia occurs as a result of HBOC administration and if the levels are significantly elevated (greater than 10%), impairment of coagulation is possible.
由于氧化作用会影响血小板和凝血因子，血红蛋白氧载体（HBOCs）中的血红蛋白自动氧化会导致其转化为高铁血红蛋白，这可能会对凝血产生累加性不良影响。本研究探讨了不同稀释度的高、低高铁血红蛋白浓度的HBOC - 200后发生凝血病的风险。
使用血栓弹力图（TEG；Haemoscope，伊利诺伊州奈尔斯市）对献血者血液进行实验室研究。
大学实验室。
志愿献血者血液。
在失血性休克临床复苏期间，用不同剂量的HBOC - 200（氧合血红蛋白；Biopure公司，马萨诸塞州剑桥市）模拟血液稀释。分析了全血与高铁血红蛋白浓度高（65%）和高铁血红蛋白浓度低（1%）的HBOC - 200按1:11、1:5、1:2和1:1稀释后与凝血病的关系。
对稀释对凝血的固定效应分析表明，HBOC - 200（低高铁血红蛋白）和HBOC - 200（高铁血红蛋白）的逐步稀释导致反应时间（R）和血块形成时间（K）显著延长，血块动力学（α）和血块强度（MA和G）显著降低。对治疗组对凝血的固定效应分析表明，与HBOC - 200（低高铁血红蛋白）相比，HBOC - 200（高铁血红蛋白）的血块形成时间（K，α）和血块强度（MA和G）有显著差异。
HBOC - 200中的高铁血红蛋白高浓度会导致累加性凝血功能损害，这可能是氧化物质对血小板功能和凝血蛋白作用的结果。氧化产物与凝血因子发生不良反应，并改变血小板中的氧化还原敏感位点。因此，如果因使用HBOC而发生高铁血红蛋白血症，且水平显著升高（大于10%），则可能会出现凝血功能损害。
