Journal of Cardiothoracic and Vascular Anesthesia
Volume 23, Issue 1 , Pages 41-47, February 2009

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

  • Mojgan Moallempour, MD

      Affiliations

    • Department of Anesthesiology, David Geffen School of Medicine at UCLA, Los Angeles, CA
    • ,
  • Jonathan S. Jahr, MD

      Affiliations

    • Department of Anesthesiology, David Geffen School of Medicine at UCLA, Los Angeles, CA
    • Corresponding Author InformationAddress reprint requests to Jonathan S. Jahr, MD, Department of Anesthesiology, David Geffen School of Medicine at UCLA, CHS 56-122, Box 951778, 650 Charles E. Young Drive South, Los Angeles, CA 90095
    • ,
  • Jennifer C. Lim

      Affiliations

    • Department of Anesthesiology, David Geffen School of Medicine at UCLA, Los Angeles, CA
    • ,
  • David Weeks, PhD, MD

      Affiliations

    • Department of Anesthesiology, University of California, San Francisco, San Francisco, CA
    • ,
  • Anthony Butch, PhD

      Affiliations

    • Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA
    • ,
  • Bernd Driessen, DVM, PhD

      Affiliations

    • Department of Clinical Sciences, University of Pennsylvania School of Veterinary Medicine, Philadelphia, PA

published online 01 September 2008.

Objectives

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.

Design

A laboratory study on donor blood using thromboelastography (TEG; Haemoscope, Niles, IL).

Setting

A university laboratory.

Participants

Volunteer donor blood.

Interventions

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.

Measurements and Main Results

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 (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).

Conclusions

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.

Key Words: methemoglobin, Oxyglobin, HBOC-200, hemoglobin-based oxygen carrier, coagulation, thromboelastography

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 J.S.J. was a principle investigator in a phase 2 and phase 3 study with Biopure. Veterinary product Oxyglobin was purchased at Veterinary Pharmacy for the purposes of this study.

PII: S1053-0770(08)00182-1

doi:10.1053/j.jvca.2008.06.006

Journal of Cardiothoracic and Vascular Anesthesia
Volume 23, Issue 1 , Pages 41-47, February 2009

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