ABSTRACT: Producing an alternative to human erythrocytes has been one the most exciting dreams of medicine. Hemoglobin-based oxygen carriers (HBOCs) derived from purified human or bovine hemoglobin have been studied for clinical use and one product is currently available in the United States and European Union for veterinary use, and another in South Africa for human use.
HBOC-201, bovine purified hemoglobin crosslinked and polymerized with glutaraldehyde, has been studied extensively in patients. We describe HBOC-201's potential market share, the history of HBOCs in general and of this compound, its pharmacology, published studies in patients and HBOCs that are currently being studied.
A literature review using PubMed listed publications and official product websites.
While HBOC-201 may not replace allogenic blood transfusions, it may serve to allow critically ill patients to be resuscitated in the field or hospital setting until either regeneration of red cell occurs or a transfusion is available.
Expert opinion on biological therapy 10/2008; 8(9):1425-33. · 3.22 Impact Factor
ABSTRACT: 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.
Journal of cardiothoracic and vascular anesthesia 09/2008; 23(1):41-7. · 1.06 Impact Factor
ABSTRACT: Because hetastarches have deleterious effects on coagulation that increase with molecular weight (MWt), risk of coagulopathy associated with a high MWt hemoglobin-based oxygen carrier (HBOC) was studied.
Preliminary laboratory study of donor blood using thromboelastography (TEG).
Volunteer donor blood.
Experiments simulated hemodilution during clinical resuscitation of hemorrhagic shock with varying doses of HBOCs. Coagulopathy related to 1:11, 1:5, 1:2, or 1:1 dilution of whole blood with normal saline, 6% hetastarch (670 kilodaltons [kD]), hemoglobin glutamer-200 (HBOC-200, 200 kD), or OxyVita (OXYVITA Inc, New Windsor, NY) (a new-generation, zero-link polymerized bovine hemoglobin-based oxygen carrier, 33 megadaltons) were analyzed.
At 2 lower levels of hemodilution, hetastarch, HBOC-200, and OxyVita produced equivalent reductions in maximum clot strength (TEG-MA and TEG-G) that reached statistical significance compared with whole blood and normal saline. At 2 higher dilutions, OxyVita and HBOC-200 impaired maximum clot strength compared with whole blood, normal saline, and hetastarch. Dilution with hetastarch had a greater effect on clot propagation (K and alpha) than either HBOC.
OxyVita and HBOC-200, HBOCs with different MWt, had similar effects on coagulation as measured by TEG. The impairment of coagulation by HBOCs and hetastarch occurred at doses corresponding to 12 mL/kg or a blood volume replacement of 17%. The use of HBOCs at doses corresponding to 23 mL/kg or a blood volume replacement of 33% significantly decreased coagulation to levels associated with increased clinical bleeding in this preliminary study. Minimal coagulopathic effects are expected with use of OxyVita at the manufacturer's anticipated effective dose of 10 g or 2 to 3 mL/kg.
Journal of cardiothoracic and vascular anesthesia 03/2008; 22(1):34-9. · 1.06 Impact Factor
ABSTRACT: The objective of this study was to determine if coagulation is different between 6% hetastarch in normal saline (NS) and 6% hetastarch in lactated Ringer's solution (LR), with use of an ex vivo thromboelastography (TEG) model with healthy donated volunteer blood. We simulated hemodilution that occurs during clinical resuscitation of hemorrhagic or hypovolemic shock, using healthy human donor whole blood (WB) ex vivo. Coagulopathy related to low, medium, high, or very high dilution of WB with NS or a high-molecular-weight hetastarch-based plasma expander, 6% hetastarch in NS (HSNS) or 6% hetastarch in lactated Ringer's [Hextend (HSLR)], was analyzed by thromboelastography (TEG). No changes were noted in the TEG profile of undiluted WB controls during the 6-hour period of use (P > 0.95). Dilution with HSNS and HSLR significantly impaired coagulation compared to both WB control and NS. Progressive dilution with NS impaired coagulation but to a lesser extent than colloids (P < 0.01). Low dilution of blood with NS increased clot strength by 12% (not significant; P = 0.097). We conclude that WB containing citrate obtained from healthy donors for TEG analysis yields reproducible data over a minimum of 6 hours. Either hetastarch, when present at concentrations comparable to the manufacturer's maximum recommended dose of 20 mL/kg (equivalent to the high dilution used in these experiments), decreases clot tensile strength to levels associated with an increased risk of bleeding. Substitution of lactated Ringer's for NS in 6% hetastarch appears to offer no advantage in avoiding hemostatic compromise in an in vitro model.
American journal of therapeutics 15(3):225-30.