Hemoglobin released into the circulation during hemolysis or therapy with chemically modified hemoglobins, exert oxidative and NO-scavenging toxic effects. Pyridoxalated hemoglobin polyoxyethylene conjugate (PHP) is one of the second-generation hemoglobin-based oxygen carriers (HBOCs). We wanted to investigate the metabolism of PHP with a special focus on its consequences for interpreting hemolysis-related diagnostic parameters in PHP-treated patients. Clinical samples were analyzed from 3 patients, who received PHP (as part of the PHOENIX phase III trial) for treatment of catecholamine-resistant distributive shock. In contrast to expectations, clearance of PHP by hemopexin, instead of haptoglobin was documented by increased hemolysis indices, absence of decreased haptoglobin values, presence of free PHP-hemoglobin and exhausted hemopexin concentrations. The present case report is important for both clinicians and laboratorians since it nicely illustrates that a hemolytic aspect of plasma is not necessarely synonymous with hemolysis. A hemolytic aspect of plasma or serum (high hemolysis index) in combination with normal or increased haptoglobin values should draw the attention; additional determination of lactate dehydrogenase and hemopexin may then be useful to distinguish the condition from in vitro hemolysis and to monitor the in vivo elimination of the heme compounds.
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Clin Chim Acta
July 2018
University of Louisville School of Medicine, Department of Pathology and Laboratory Medicine, 511 S. Floyd Street, Louisville, KY 40202, USA. Electronic address:
Background: There are 13 million blood transfusions each year in the US. Limitations in the donor pool, storage capabilities, mass casualties, access in remote locations and reactivity of donors all limit the availability of transfusable blood products to patients. HBOC-201 (Hemopure®) is a second-generation glutaraldehyde-polymer of bovine hemoglobin, which can serve as an "oxygen bridge" to maintain oxygen carrying capacity while transfusion products are unavailable.
View Article and Find Full Text PDFBiomolecules
January 2017
Laboratory of Biochemistry and Vascular Biology, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20993, USA.
Intense efforts have been made by both industry and academia over the last three decades to produce viable hemoglobin (Hb)-based oxygen carriers (HBOCs), also known as "blood substitutes". Human trials conducted so far by several manufactures in a variety of clinical indications, including trauma, and elective surgeries have failed and no product has gained the Food and Drug Administration approval for human use. Safety concerns due to frequent incidences of hemodynamic, cardiac events, and even death led to the termination of some of these trials.
View Article and Find Full Text PDFActa Clin Belg
March 2014
Department of Laboratory Medicine, Ghent University Hospital, Belgium.
Hemoglobin released into the circulation during hemolysis or therapy with chemically modified hemoglobins, exert oxidative and NO-scavenging toxic effects. Pyridoxalated hemoglobin polyoxyethylene conjugate (PHP) is one of the second-generation hemoglobin-based oxygen carriers (HBOCs). We wanted to investigate the metabolism of PHP with a special focus on its consequences for interpreting hemolysis-related diagnostic parameters in PHP-treated patients.
View Article and Find Full Text PDFResuscitation
March 2012
Department of Emergency Medicine, Brigham and Women's Hospital and Massachusetts General Hospital, 75 Francis Street, Boston, MA 02115, USA.
Hemorrhagic shock is a pathologic state in which intravascular volume and tissue oxygen delivery are impaired, leading to circulatory collapse and cellular ischemia. Resuscitation with hemoglobin-based oxygen carriers (HBOCs) is appealing in that their use can both restore intravascular volume and tissue oxygenation, without the limitations in supply and immunomodulatory effects of packed red blood cells. However, the development of safe and effective agents has been elusive.
View Article and Find Full Text PDFCurr Drug Discov Technol
September 2012
David Geffen School of Medicine at UCLA, Ronald Reagan UCLA Medical Center, 757 Westwood Plaza, Los Angeles, CA 90095, USA.
Blood substitutes, especially hemoglobin based oxygen carriers (HBOC) have been widely studied and reviewed over the past 30 years. The development of HBOCs was highlighted by crosslinking to minimize adverse effects. However, even early attempts at single crosslinking using alpha-alpha crosslinks or diaspirin crosslinking failed clinical trials due to renal morbidity and increased mortality.
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