Methemoglobin Effects on Coagulation: A Dose-Response Study With HBOC-200 (Oxyglobin) in a Thrombelastogram Model

ObjectivesBecause 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.DesignA laboratory study on donor blood using thromboelastography (TEG; Haemoscope, Niles, IL).SettingA university laboratory.ParticipantsVolunteer donor blood.InterventionsBlood 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.Measurements and Main ResultsAnalysis 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 (α) and clot strength (MA and G). Analysis of fixed effects of treatment group on coagulation showed that clot propagation (K, α) and clot strength (MA and G) are significantly different in HBOC-200 (high methemoglobin) compared with HBOC-200 (low methemoglobin).ConclusionsHigh 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.