In vitro effects of a novel hemoglobin-based oxygen carrier on routine chemistry, therapeutic drug, coagulation, hematology, and blood bank assays

Abstract

Red blood cell (RBC) replacement solutions are being developed as alternatives to allogeneic RBC use in blood transfusions in the treatment of massive trauma, to achieve hemodynamic stability during elective surgery, and to increase oxygen-carrying capacity in anemia. Hemoglobin-based oxygen carrier (HBOC)-201 (Biopure Corp.) is a purified, sterile, isosmotic glutaraldehyde-polymerized bovine hemoglobin. Because this product is acellular, blood components containing this substance appear hemolyzed. This study reports on the interferences produced by the presence of HBOC-201 in a variety of clinical assays. This product was added in vitro at concentrations up to 60 g/L (6.0 g/dL) to normal human serum, plasma, or whole blood before testing for serum chemistries, coagulation profiles, and hematology and blood bank assays. In addition, a set of normal human sera containing HBOC-201 was supplemented with various therapeutic drugs and assayed for these agents. The results of these studies demonstrate that the presence of HBOC-201 in blood components does not result in significant analytical interference that would be of concern with many clinical assays at HBOC-201 concentrations encountered during routine clinical use of this RBC replacement solution in patients.

Oxygen Saturation Measurements in Canine Blood Containing Hemoglobin Glutamer‐200 (Bovine): In Vitro Validation of the NOVA CO‐Oximeter

“…Oxygen saturation measured by co‐oximetry represents the percentage of oxy‐Hb, expressed as a fraction of total Hb (oxy‐Hb plus deoxy‐Hb). Serum containing polymerized bovine Hb solution, whether oxygen saturated or not, has been demonstrated to display absorption peaks at 415,540, and 576 nm, which are characteristic of oxy‐Hb, 24 and, therefore, may interfere with cooximetry accuracy. In contrast to native canine Hb, which is virtually fully O 2 ‐saturated under room air conditions (21% O 2 ; arterial PO 2 ∼ 100 mm Hg) and body temperature, bovine HBOC solutions such as Hb‐200 and HBOC‐201 are only 83–85% oxygen saturated under the same conditions because of their higher P 50 of 34–38 mm Hg 7,8 .…”

“…Typically, absorption spectra are measured at different wavelengths in the 500‐to 670‐nm band (eg, 535.0,585.2,594.5, and 626.6 nm). Blood containing foreign stroma‐free Hb might have oxy‐Hb absorption peaks different from that of native blood 24 …”

“…Moreover, blood gas analyzers and co‐oximeters usually compute oxygen content (O 2 ct) based on the oxygen‐binding capacity (Hüfner factor: 1.39 mL/g) 23 of human Hb. For these reasons, it is necessary to use different equations for calculations of Hb saturation and total blood O 2 ct when blood that contains xenogeneic Hb is analyzed 21,24 …”

Developmental toxicity in rats of a hemoglobin-based oxygen carrier results from impeded function of the inverted visceral yolk sac

“…Following mating, groups of eight animals were assigned to HBOC-201 and saline control groups to be used in hemodilution studies performed to assess whether anemia or osmotic pressure 1 Hetastarch was used to control for oncotic effects. The osmolality of 6% hetastarch is 309 mOm [44]; the osmolality of HBOC-201 is calculated to be 290-310 mOsm [45] Due to molecular weight differences (HBOC is approximately 250 kD; hetastarch is approximately 800 kD), 45 mL/kg of HBOC-201 at the high dose results in 5.85 g HBOC/kg whereas 45 mL of hetastarch results in 2.7 g/kg. changes contribute to developmental toxicity.…”

Die Qualität diagnostischer Proben

“…Bei Verwendung von Ha Èmoglobinderivaten ist eine sichtbare Ha Èmoglobinkonzentration im Bereich von 10±50 g/L typisch. Sie ist durch das Absorptionsspektrum kaum von natu Èrlichem Ha Èmoglobin zu unterscheiden [35,36,37,43]. Da jedoch Ha Èmoglobinkonzentrationen in diesem Ausmaû in vivo selten vorkommen, ist allein durch die Ho Èhe der Ha Èmoglobinkonzentration eine Verwendung von therapeutischen Ha Èmoglobinderivaten anzunehmen.…”