HbO

Hemoglobin Oxygen Therapeutics LLC

About

Hemoglobin Oxygen Therapeutics LLC (HbO2 Therapeutics) is a leading developer and manufacturer of oxygen carrying solutions, a class of drug products that when administered intravenously can increase the amount of oxygen transported throughout the body. We have developed two products. Hemopure® [hemoglobin glutamer – 250 (bovine)], for use in humans, and Oxyglobin® [hemoglobin glutamer – 200 (bovine)]) for veterinary use. Oxyglobin is the only oxygen carrying solution approved by the FDA and the European Medicines Agency (EMA) to treat all cause canine anemia. Hemopure is approved in South Africa to treat adult surgical patients who are anemic, and in the Russian Federation for acute anemia, irrespective of etiology. In the US Hemopure is only available under investigational status through the FDA expanded access program to qualifying patients with severe, life threatening anemia for whom blood transfusion is not an option, and who have exhausted all other treatment options. Blood transfusion may not be an option due to religious beliefs, or because no compatible blood is available for a patient needing transfusion. Additional information on expanded access can be found here.

There are more reasons why an oxygen-carrying solution such as Hemopure® is preferred over blood including organ transplantations and blood transfusions.  In the video below, Robert J Porte, MD, PhD, Professor of Surgery at the University of Groningen, The Netherlands shares his experience with Hemopure®  when used to refurbish discarded livers.

When our products are infused into the bloodstream, the chemically stabilized hemoglobin molecules carry oxygen in the plasma (the fluid part of blood) and can also facilitate the release of oxygen from remaining red blood cells (RBC), thereby increasing diffusion of oxygen to tissues. If necessary, this effect can be extended over time by repeat dosing to provide a continuous oxygen bridge until the patients receive other appropriate therapy.

Hemoglobin, the native protein responsible for transporting oxygen is normally contained within circulating RBCs. However, our products consist of hemoglobin that has been extracted from the RBCs of cattle and then purified, chemically cross-linked for stability and formulated in a balanced salt solution similar to Lactated Ringer’s Solution.

On a gram-for-gram basis, stabilized hemoglobin molecules in our products hold the same amount of oxygen as the hemoglobin molecules in RBCs, but with a higher P50 (40 mm Hg), they release the oxygen more readily. In addition, data from preclinical studies suggest that introducing our products into the bloodstream may help RBCs offload more oxygen to the tissues than they would otherwise.

Scientific advisory board

HbO2 Therapeutics collaborates with institutions and key opinion leaders around the world. They include, but are not limited to specialists in transfusion medicine, cardiology, trauma surgery, hematology/oncology, and transplantation.

Management

Led by a team with decades of success

Mr. Zafirelis has more than 25 years of CEO experience in private and public companies, including start-up ventures and turnaround situations. He led the original team at Biopure that developed Oxyglobin®, the veterinary oxygen carrier, now approved by FDA and EMA. Previously he led two cardiac device (class 3) companies, Cardiac Assist (Tandemheart) and Medquest Products and has significant experience with regulatory agencies worldwide. Mr. Zafirelis has an MS in Chemistry and an MBA from the University of Southern California. He has also completed the Corporate Director Program at Harvard Business School.

Mr. Serov has over 20 years of experience in the Investment Banking industry. He spent most of his career in London running such groups as capital markets, structured products, and advisory. Mr. Serov has worked at Bankers Trust, Rose Square Capital, Dresdner Kleinwort Benson, and Renaissance Capital. Before joining Hemoglobin Oxygen Therapeutics, he was heading up coverage for corporate clients and financial institutions at Sberbank, the largest Russian bank. Mr. Serov has a BA in Mathematics and Economics from Connecticut College.

Mr. Uberoi is a seasoned communications strategist who has worked in senior roles in a variety of blue chip companies including Pfizer, Johnson & Johnson, S&P  as well as a number of biotech companies including Elan and Agenus. Sunny has led communications for several mergers and acquisitions, and was the architect for the first digital security asset launched by a publicly traded company.

Mr. Leibensperger has 22 years of experience in Biopharmaceutical Manufacturing and Operations Management. He was an original team member with Biopure Corp. that helped bring Oxyglobin® and Hemopure® production to full scale and an integral part of achieving FDA and EMA GMP approval for manufacturing facilities. Bruce has had direct responsibilities for addressing FDA, EMA, and MHRA regulatory agencies. Most recently served as a Plant Director at OPK Biotech LLC and was responsible for restart operations. Employing Lean Manufacturing principles, the OPK Biotech Souderton Facility was fully operational ahead of schedule and gained VMD approval for veterinary product marketing. Previously, he served as a Biomaterials Manufacturing Manager at Globus Medical Inc. where he managed restructuring of department personnel and multiple production lines including polymer-based bone void implants, and spinal implant devices that gained both FDA and EU marketing approval. Mr. Leibensperger has a B.S. degree in Biology from Susquehanna University.

Mr. Dawson has over 25 years experience working with the development and commercialization of Hemopure and Oxyglobin. In this position with Hemoglobin Oxygen Therapeutics LLC, Mr. Dawson is responsible for the transition of the manufacturing process and components from the Cambridge, MA manufacturing facility to the Souderton, PA manufacturing facility. Mr. Dawson started his career with Biopure in 1989 and held several positions in manufacturing operations offering broad qualifications in all facets of production, maintenance, calibration, supply chain, process engineering, validation, environmental control, anaerobic aseptic filling, packaging, microbiology and capacity management. The scope of Mr. Dawson’s experience encompasses preclinical research and development phase through product approval and marketing. He is successful in streamlining production processes, accelerating performance, reducing costs, and meeting time-critical industry demands. Brian was Director of Operations for both Biopure and OPK Biotech LLC, and has a BA from North Adams State College (Massachusetts College of Liberal Arts).

Gregory Dubé has over 30 years of industry experience in drug research and development including leadership positions in large pharma, small pharma, biotechnology and start-up firms. This history includes management roles at Biopure Corporation, OPK Biotech, LLC and Hemoglobin Oxygen Therapeutics. Dr. Dubé has a deep understanding of the physical, biochemical and pharmacological properties of hemoglobin-based oxygen carriers (HBOCs) and has significant experience in the design and conduct of preclinical and clinical studies to evaluate HBOCs across a wide range of clinical indications, including donor organ perfusion, organ ischemia/reperfusion injury, hemorrhagic trauma/shock, anemia and heart failure.  Dr. Dubé has a doctorate in pharmacology and cell biophysics from the University of Cincinnati College of Medicine and completed a postdoctoral fellowship at Duke University School of Medicine, Division of Cardiology.

Mr. Meng is a Hemoglobin specialist with 20 years of research experience in developing hemoglobin-based oxygen carriers (HBOCS). In 2014, he received ORISE-advanced scientist fellowship from FDA, and worked in the Biochemistry and Vascular Laboratory at the Office of Blood Research and Review for 5 years. Previously he spent 10 years as post-doctoral fellow/instructor at Albert Einstein College of Medicine. He holds a PhD from the National Key Lab of Biochemical Engineering, Chinese Academy of Sciences, China.

Mr. Pitman has 20 years of broad based pharmaceutical and healthcare US experience with a strong background in mathematics, statistics and logistics. Previously he has taught courses in mathematics, logic, computer sciences and statistics at various colleges, including the University of Kharkov, Ukraine, Soviet Union. He earned a Master of Science with Honors in mathematics at Kharkov State University, USSR.

Ms. Zafirelis has more than 20 years of multinational regulatory and clinical operations experience. She has a BA from University of Massachusetts and a MBA from the University of Southern California, Marshall School of Business.

Mrs. Howes has 19 years of Manufacturing, Validation, and Quality experience. Previously, Serena has worked at such places as Regeneron Pharmaceuticals, Abbott, and Sanofi where she held positions of increasing responsibility such as managing validation groups and leading many lean initiatives to streamline quality CAPA systems, training, and validation processes through Six Sigma and lean continuous improvement tools. Serena has held responsibility for interacting with and addressing regulatory agencies such as FDA, EMA, MHRA, Japan, Irish Medical Board, and Turkish Ministry. Serena holds a B.S. In Biology from Siena College in Loudonville, NY.

Manufacturing

Source of hemoglobin and viral safety

Hemopure and Oxyglobin are sourced from bovine red blood cells (RBCs). The Hemoglobin (Hb) found in RBCs is extracted, purified and chemically cross-linked (polymerized) for stability, and formulated in a Lactated Ringer’s Solution. Our quality management system includes a comprehensive herd management program to ensure the safety of all raw material used in production. All sourced cattle are born in the USA or Canada and obtained from pre-qualified suppliers that maintain comprehensive health and feed histories for each animal. All collected material is held in quarantine until a post mortem inspection of the cattle is conducted by the onsite USDA veterinarian, and released for human consumption. Additionally, our products hold certificates of suitability (CEP) for TSE from the European Directorate for the Quality of Medicines & Healthcare (EDQM) that certifies compliance with the European Pharmacopoeia general chapter 5.2.8 ‘Minimizing the risk of transmitting animal spongiform encephalopathy agents via medicinal products’.

Manufacturing process

Our products are manufactured by an extensive purification procedure. The purification of hemoglobin involves an automated state-of- the-art process consisting of multiple separation and filtration steps including specific hemoglobin isolation by large-scale, high-pressure ion exchange liquid chromatography. During the manufacturing process hemoglobin is crosslinked and polymerized by reaction with glutaraldehyde under totally automated procedures. We have recently consolidated all manufacturing activities at our site in Souderton PA, where the facility is undergoing a multimillion dollar expansion to accommodate increased capacity for all production steps from collection of starting materials through aseptic fill finish.

Oxygen carrying solutions

Why an oxygen carrying solution?

Oxygen is indispensable to the life of all human tissues. Hemoglobin, a protein normally contained within red blood cells (RBCs), carries and releases oxygen to the body’s tissues. Medical conditions such as ischemia or anemia can compromise tissue oxygenation. Ischemia is a decrease or lack of RBC flow to an organ or body part due to obstructed or constricted blood vessels, as in heart attack, stroke and certain medical procedures. Anemia is a deficiency of RBCs or hemoglobin associated with blood loss (e.g., from injury or surgery) or other disorders. Oxygen deprivation, even for several minutes, can result in cell damage, organ dysfunction and, if prolonged, death.

The most critical property of each product is an ability to efficiently transport oxygen. There are two mechanisms by which oxygen transport is enhanced. Promoting both convective and diffusive oxygen delivery; the net result is an increase in oxygen delivery due to both an increase in the oxygen-carrying capacity of the plasma, and changes in the rheology of blood. HBOC-201 has a viscosity of 1.3 centipoise, about 1/3 of that of blood. Addition of HBOC-201 to blood decreases the overall viscosity. The products increase plasma and total hemoglobin concentration and thus increases arterial oxygen content.

Research areas

Our priority is the clinical development of Hemopure, (i) as a perfusion fluid in organ transplantation, (ii) Oxygen carrying support in severe anemia where blood is not an option and (iii) for ischemia/infarct reduction in patients with large anterior wall myocardial infarctions.

Hemopure

Hemopure is universally compatible and requires no type or cross match prior to intravenous administration through a standard infusion set. Supplied in sterile IV infusion bags, the product is ready to be administered. No reconstitution or other preparation is required. Hemopure also does not need refrigeration and remains stable at room temperature for at least three years.

Normal blood flow

Anemic blood flow

Published Literature

Hemopure and Oxyglobin have to date been the topic of over 200 peer reviewed journal articles, conference proceeding and posters

The following reference list includes many of those, but is by no means all inclusive. The references are date ordered with the most recent first:

de Vries Y, Matton APM, Nijsten MWN, Werner MJM, van den Berg AP, de Boer MT, Buis CI, Fujiyoshi M, de Kleine RHJ, van Leeuwen OB, Meyer P, van den Heuvel MC, de Meijer VE, Porte RJ.  Am J Transplant. 2018 Dec 26. doi: 10.1111/ajt.15228. [Epub ahead of print] PubMed PMID: 30588774.
Pretransplant Sequential Hypo- and Normothermic Machine Perfusion of Suboptimal Livers Donated after Circulatory Death Using a Hemoglobin-based Oxygen Carrier Perfusion Solution.
Quintini C, Lomaglio L, Pezzati D, Diago Uso T, Liu Q. Liver Transpl. 2018 Oct 29. doi: 10.1002/lt.25370. [Epub ahead of print] PubMed PMID: 30371975.
Combined hypothermic and normothermic perfusion for the optimization of injured liver grafts.

Boteon YL, Laing RW, Schlegel A, Wallace L, Smith A, Attard J, Bhogal RH, Neil DA, Hübscher S, Perera MTP, Mirza DF, Afford SC, Mergental H.Liver Transpl. 2018 Jul 30. doi: 10.1002/lt.25315. [Epub ahead of print] PMID: 30058119

 
Combined Hypothermic and Normothermic Machine Perfusion Improves Functional Recovery of Extended Criteria Donor Livers
de Vries Y, van Leeuwen OB, Matton APM, Fujiyoshi M, de Meijer VE, Porte RJ. Transpl Int. 2018 Nov;31(11):1281-1282. doi: 10.1111/tri.13320. Epub 2018 Aug 13. PubMed PMID: 30055059.
Ex situ normothermic machine perfusion of donor livers using a haemoglobin‐based oxygen carrier: a viable alternative to red blood cells
Henderson, Reney et al. Journal of Cardiothoracic and Vascular Anesthesia. 2018 In press.
A Bridge to Bloodless Surgery: Use of Hemoglobin-Based Oxygen Carrier for Anemia Treatment and Autologous Blood Preservation During Redo Pulmonic Valve Replacement
Dolgin E. Nature. 2017 Sep 27;549(7673):S12-S15. doi: 10.1038/549S12a.
Doing without donors. Stem cells and artificial substitutes could ease the dependence on blood donations.
Keipert PE. Adv Exp Med Biol. 2017;977:343-350. doi: 10.1007/978-3-319-55231-6_45.
Hemoglobin-Based Oxygen Carrier (HBOC) Development in Trauma: Previous Regulatory Challenges, Lessons Learned, and a Path Forward.
Laing RW, Bhogal RH, Wallace L, Boteon Y, Neil DAH, Smith A, Stephenson BTF, Schlegel A, Hübscher SG, Mirza DF, Afford SC, Mergental H. Transplantation. 2017 Nov;101(11):2746-2756. doi: 10.1097/TP.0000000000001821.
The Use of an Acellular Oxygen Carrier in a Human Liver Model of Normothermic Machine Perfusion.
Gomez MF, Aljure O, Ciancio G, Lynn M. Am J Transplant. 2017 Jul;17(7):1941-1944. doi: 10.1111/ajt.14226. Epub 2017 Mar 17.
Hemoglobin-Based Oxygen Carrier Rescues Double-Transplant Patient From Life-Threatening Anemia.
García-Ruiz JM, Galán-Arriola C, Fernández-Jiménez R, Aguero J, Sánchez-González J, García-Alvarez A, Nuno-Ayala M, Dubé GP, Zafirelis Z, López-Martín GJ, Bernal JA, Lara-Pezzi E, Fuster V, Ibáñez B. Basic Res Cardiol. 2017 Mar;112(2):17. doi: 10.1007/s00395-017-0605-6. Epub 2017 Feb 10.
Bloodless reperfusion with the oxygen carrier HBOC-201 in acute myocardial infarction: a novel platform for cardioprotective probes delivery.
Mer M, Hodgson E, Wallis L, Jacobson B, Levien L, Snyman J, Sussman MJ, James M, van Gelder A, Allgaier R, Jahr JS. Transfusion. 2016 Oct;56(10):2631-2636. doi: 10.1111/trf.13726. Epub 2016 Sep 23.
Hemoglobin glutamer-250 (bovine) in South Africa: consensus usage guidelines from clinician experts who have treated patients.
Epperla N, Strouse C, VanSandt AM, Foy P. Transfusion. 2016 Jul;56(7):1801-6. doi: 10.1111/trf.13607. Epub 2016 Apr 6.
Difficult to swallow: warm autoimmune hemolytic anemia in a Jehovah's Witness treated with hemoglobin concentrate complicated by achalasia.
Black V, Adamantos S, Barfield D, Tasker S. J Feline Med Surg. 2016 Aug;18(8):597-602. doi: 10.1177/1098612X15588800. Epub 2015 Jun 26.
Feline non-regenerative immune-mediated anaemia: features and outcome in 15 cases.
Raines JA, Storms T. J Zoo Wildl Med. 2015 Mar;46(1):161-3.
A successful transfusion in a tamandua (Tamandua tetradactyla) using both whole blood and blood replacement products.
Holson JF, Stump DG, Pearce LB, Watson RE, DeSesso JM. Reprod Toxicol. 2015 Apr;52:101-7. doi: 10.1016/j.reprotox.2015.01.006. Epub 2015 Feb 16.
Absence of developmental toxicity in a canine model after infusion of a hemoglobin-based oxygen carrier: Implications for risk assessment.
Stump DG, Holson JF, Harris C, Pearce LB, Watson RE, DeSesso JM. Reprod Toxicol. 2015 Apr;52:108-17. doi: 10.1016/j.reprotox.2015.01.005. Epub 2015 Jan 21.
Developmental toxicity in rats of a hemoglobin-based oxygen carrier results from impeded function of the inverted visceral yolk sac.
Peruski AM, Cooper ES, Butler AL. Am J Vet Res. 2014 Jan;75(1):77-84. doi: 10.2460/ajvr.75.1.77.
Microcirculatory effects of a hyperviscous hemoglobin-based solution administered intravenously in dogs with experimentally induced hemorrhagic shock.
Weiskopf RB. Anesth Analg. 2014 Oct;119(4):758-60. doi: 10.1213/ANE.0000000000000401.
Hemoglobin-based oxygen carriers: disclosed history and the way ahead: the relativity of safety.
Song BK, Nugent WH, Moon-Massat PF, Pittman RN. Microvasc Res. 2014 Sep;95:124-30. doi: 10.1016/j.mvr.2014.07.005. Epub 2014 Jul 18.
Effects of a hemoglobin-based oxygen carrier (HBOC-201) and derivatives with altered oxygen affinity and viscosity on systemic and microcirculatory variables in a top-load rat model.
Van Hemelrijck J, Levien LJ, Veeckman L, Pitman A, Zafirelis Z, Standl T. Anesth Analg. 2014 Oct;119(4):766-76. doi: 10.1213/ANE.0000000000000305.
A safety and efficacy evaluation of hemoglobin-based oxygen carrier HBOC-201 in a randomized, multicenter red blood cell controlled trial in noncardiac surgery patients.
Lundy JB, Lewis CJ, Cancio LC, Cap AP. Int J Burns Trauma. 2014 Feb 22;4(1):45-8. eCollection 2014.
Experience with the use of Hemopure in the care of a massively burned adult.
Donner MG, Topp SA, Cebula P, Krienen A, Gehrmann T, Sommerfeld A, Reinehr R, Macher A, Herebian D, Mayatepek E, Pannen BH, Knoefel WT, Häussinger D. Biol Chem. 2013 Jan;394(1):97-112. doi: 10.1515/hsz-2012-0153.
HbG200-mediated preinduction of heme oxygenase-1 improves bile flow and ameliorates pericentral downregulation of Bsep and Mrp2 following experimental liver ischemia and reperfusion.
Abutarboush R, Scultetus A, Pappas G, Arnaud F, Auker C, McCarron R, Moon-Massat PF. Curr Drug Discov Technol. 2013 Dec;10(4):315-24.
Effects of N-acetyl-L-cysteine and hyaluronic acid on HBOC-201-induced systemic and cerebral vasoconstriction in the rat.
Galvagno SM Jr, Mackenzie CF. Anesthesiol Clin. 2013 Mar;31(1):1-19. doi: 10.1016/j.anclin.2012.10.004. Epub 2012 Dec 6. Review.
New and future resuscitation fluids for trauma patients using hemoglobin and hypertonic saline.
Jordan SD, Alexander E. J Pharm Pract. 2013 Jun;26(3):257-60. doi: 10.1177/0897190012451928. Epub 2012 Aug 6.
Bovine hemoglobin: a nontraditional approach to the management of acute anemia in a Jehovah's Witness patient with autoimmune hemolytic anemia.
Zhou Y, Cabrales P, Palmer AF. Biophys Chem. 2012 Mar;162:45-60. doi: 10.1016/j.bpc.2011.12.006. Epub 2012 Jan 9.
Simulation of NO and O2 transport facilitated by polymerized hemoglobin solutions in an arteriole that takes into account wall shear stress-induced NO production.
Arnaud F, Scultetus AH, Haque A, Saha B, Kim B, Auker C, Moon-Massat P, McCarron R, Freilich D. Resuscitation. 2012 Aug;83(8):1038-45. doi: 10.1016/j.resuscitation.2012.01.018. Epub 2012 Jan 28.
Sodium nitroprusside ameliorates systemic but not pulmonary HBOC-201-induced vasoconstriction: an exploratory study in a swine controlled haemorrhage model.
Haque A, Arnaud F, Teranishi K, Okada T, Kim B, Moon-Massat PF, Auker C, McCarron R, Freilich D, Scultetus AH. Artif Cells Blood Substit Immobil Biotechnol. 2012 Feb;40(1-2):44-55. doi: 10.3109/10731199.2011.585615. Epub 2011 Aug 2.
Pre-hospital resuscitation with HBOC-201 and rFVIIa compared to HBOC-201 alone in uncontrolled hemorrhagic shock in swine.
Jahr JS, Akha AS, Holtby RJ. Curr Drug Discov Technol. 2012 Sep;9(3):158-65. Review.
Crosslinked, polymerized, and PEG-conjugated hemoglobin-based oxygen carriers: clinical safety and efficacy of recent and current products.
Moon-Massat P, Scultetus A, Arnaud F, Brown A, Haque A, Saha B, Kim B, Sagini E, McGwin G Jr, Auker C, McCarron R, Freilich D. Injury. 2012 May;43(5):638-47. doi: 10.1016/j.injury.2010.10.013. Epub 2010 Nov 20.
The effect HBOC-201 and sodium nitrite resuscitation after uncontrolled haemorrhagic shock in swine.
Wehausen CE, Kirby R, Rudloff E. J Am Vet Med Assoc. 2011 Apr 1;238(7):909-14. doi: 10.2460/javma.238.7.909.
Evaluation of the effects of bovine hemoglobin glutamer-200 on systolic arterial blood pressure in hypotensive cats: 44 cases (1997-2008).
Vázquez BY, Hightower CM, Martini J, Messmer C, Frienesenecker B, Corbels P, Tsai AG, Intaglietta M. Crit Care Med. 2011 Jun;39(6):1461-6. doi: 10.1097/CCM.0b013e3182120cdb.
Vasoactive hemoglobin solution improves survival in hemodilution followed by hemorrhagic shock.
Donati F, Mazzarino M, de la Torre X, Botrè F, Islam N, Cowan D. Electrophoresis. 2011 Oct;32(20):2915-8. doi: 10.1002/elps.201100178. Epub 2011 Sep 16.
A simple and rapid pre-confirmation method to distinguish endogenous human haemoglobin from synthetic haemoglobin-based oxygen carriers in doping control.
Auker CR, McCarron RM. J Trauma. 2011 May;70(5 Suppl):S40-1. doi: 10.1097/TA.0b013e31821a5a1e. Review.
US Navy experience with research on, and development of, hemoglobin-based oxygen carriers.
Minei JP. J Trauma. 2011 May;70(5 Suppl):S38-9. doi: 10.1097/TA.0b013e31821a5a09. Review.
Is there a role for hemopure in the prehospital setting?
Wondratschek C, Weingart C, Kohn B. J Am Anim Hosp Assoc. 2010 Jan-Feb;46(1):12-9.
Primary immune-mediated thrombocytopenia in cats.
Greenburg AG, Light WR, Dubé GP. Transfusion. 2010 Dec;50(12):2764-7; author reply 2767. doi: 10.1111/j.1537-2995.2010.02814.x.
Reconstructing hemoglobin-based oxygen carriers.
Donahue LL, Shapira I, Shander A, Kolitz J, Allen S, Greenburg G. Transfusion. 2010 Jul;50(7):1561-7. doi: 10.1111/j.1537-2995.2010.02603.x. Epub 2010 Apr 23. Review.
Management of acute anemia in a Jehovah's Witness patient with acute lymphoblastic leukemia with polymerized bovine hemoglobin-based oxygen carrier: a case report and review of literature.
Weiskopf RB. Anesth Analg. 2010 Mar 1;110(3):659-62. doi: 10.1213/ANE.0b013e3181c85255.
Hemoglobin-based oxygen carriers: compassionate use and compassionate clinical trials.
Katz LM, Manning JE, McCurdy S, Sproule C, McGwin G Jr, Moon-Massat P, Cairns CB, Freilich D. Resuscitation. 2010 Apr;81(4):481-7. doi: 10.1016/j.resuscitation.2009.12.015. Epub 2010 Jan 18.
Nitroglycerin attenuates vasoconstriction of HBOC-201 during hemorrhagic shock resuscitation.
Singleton CL, Oosterhuis JE, Seibold K, Lamberski N. J Zoo Wildl Med. 2009 Jun;40(2):378-81.
Successful treatment of a southern Pacific rattlesnake (Crotalus viridis helleri) bite in a caracal (Caracal caracal).
Moallempour M, Jahr JS, Lim JC, Weeks D, Butch A, Driessen B. J Cardiothorac Vasc Anesth. 2009 Feb;23(1):41-7. doi: 10.1053/j.jvca.2008.06.006. Epub 2008 Aug 29.
Methemoglobin effects on coagulation: a dose-response study with HBOC-200 (Oxyglobin) in a thrombelastogram model.
Kubulus D, Mathes A, Reus E, Pradarutti S, Pavlidis D, Thierbach JT, Heiser J, Wolf B, Bauer I, Rensing H. Shock. 2009 Aug;32(2):179-89. doi: 10.1097/SHK.0b013e318199352b.
Endothelin-1 contributes to hemoglobin glutamer-200-mediated hepatocellular dysfunction after hemorrhagic shock.
Lichtenberger M, Orcutt C, Cray C, Thamm DH, DeBehnke D, Page C, Mull L, Kirby R. J Vet Emerg Crit Care (San Antonio). 2009 Oct;19(5):467-72. doi: 10.1111/j.1476-4431.2009.00465.x.
Comparison of fluid types for resuscitation after acute blood loss in mallard ducks (Anas platyrhynchos).
Lee J, Kim JG, Mahon S, Tromberg BJ, Mukai D, Kreuter K, Saltzman D, Patino R, Goldberg R, Brenner M. J Biomed Opt. 2009 Jul-Aug;14(4):044027. doi: 10.1117/1.3200932.
Broadband diffuse optical spectroscopy assessment of hemorrhage- and hemoglobin-based blood substitute resuscitation.
Weingart C, Kohn B. J Feline Med Surg. 2008 Oct;10(5):431-8. doi: 10.1016/j.jfms.2007.10.012. Epub 2008 May 2.
Clinical use of a haemoglobin-based oxygen carrying solution (Oxyglobin) in 48 cats (2002-2006).
Topp SA, Krieg A, Koch A, Tidden CM, Ramp U, Hohlfeld T, Macher A, Schulte am Esch J 2nd, Eisenberger CF, Stoecklein NH, Knoefel WT. J Surg Res. 2008 Dec;150(2):243-54. doi: 10.1016/j.jss.2008.02.033. Epub 2008 Mar 18.
Hemoglobin-glutamer 200 reduces reperfusion injury of the cold preserved rat liver by induction of heme oxygenase-1.
Jahr JS, Lurie F, Bezdikian V, Driessen B, Gunther RA. Am J Ther. 2008 Mar-Apr;15(2):98-101. doi: 10.1097/MJT.0b013e31804c6f98.
Measuring circulating blood volume using infused hemoglobin-based oxygen carrier (oxyglobin) as an indicator: verification in a canine hypovolemia model.
Rempf C, Ritter A, Schrepfer S, Freitag M, Standl T, Gottschalk A. Artif Cells Blood Substit Immobil Biotechnol. 2008;36(1):34-44. doi: 10.1080/10731190701857769.
Failed induction of heme oxygenase 1 in endothelial cells exposed to the hemoglobin based oxygen carrier Oxyglobin.
Jahr JS, Weeks DL, Desai P, Lim JC, Butch AW, Gunther R, Driessen B. J Cardiothorac Vasc Anesth. 2008 Feb;22(1):34-9. doi: 10.1053/j.jvca.2007.02.016. Epub 2007 May 24.
Does OxyVita, a new-generation hemoglobin-based oxygen carrier, or oxyglobin acutely interfere with coagulation compared with normal saline or 6% hetastarch? An ex vivo thromboelastography study.
Driessen B, Zarucco L, Gunther RA, Burns PM, Lamb SV, Vincent SE, Boston RA, Jahr JS, Cheung AT. Crit Care Med. 2007 Sep;35(9):2101-9.
Effects of low-volume hemoglobin glutamer-200 versus normal saline and arginine vasopressin resuscitation on systemic and skeletal muscle blood flow and oxygenation in a canine hemorrhagic shock model.
Rivera-Chavez FA, Huerta S, Brown R, York GB, Minei JP. J Trauma. 2007 Nov;63(5):1113-9.
Resuscitation from hemorrhagic shock comparing standard hemoglobin-based oxygen carrier (HBOC)-201 versus 7.5% hypertonic HBOC-201.
Arnaud F, Fasipe D, Philbin N, Rice J, Flournoy WS, Ahlers S, McCarron R, Freilich D. Transfusion. 2007 Nov;47(11):2098-109.
Hematology patterns after hemoglobin-based oxygen carrier resuscitation from severe controlled hemorrhage with prolonged delayed definitive care.
VanderMolen C, Malkevich N, Philbin N, Rice J, Collier S, Hall C, Ahlers S, McCarron R, Freilich D, McGwin G, Pearce LB. Artif Cells Blood Substit Immobil Biotechnol. 2007;35(5):507-17.
Immune effects of decreasing low-molecular weight hemoglobin components of hemoglobin-based oxygen carriers (HBOC) in a swine model of severe controlled hemorrhagic shock.
Wang TY, Rao SV. Am J Cardiovasc Drugs. 2007;7(4):225-33. Review.
Anemia in patients undergoing percutaneous coronary intervention: current issues and future directions.
Cheung AT, Duong PL, Driessen B, Chen PC, Jahr JS, Gunther RA. Clin Hemorheol Microcirc. 2006;34(1-2):325-34.
Systemic function, oxygenation and microvascular correlation during treatment of hemorrhagic shock with blood substitutes.
Freitag M, Standl TG, Kleinhans H, Gottschalk A, Mann O, Rempf C, Bachmann K, Gocht A, Petri S, Izbicki JR, Strate T. Pancreatology. 2006;6(3):232-9. Epub 2006 Mar 9.
Improvement of impaired microcirculation and tissue oxygenation by hemodilution with hydroxyethyl starch plus cell-free hemoglobin in acute porcine pancreatitis.
Driessen B, Jahr JS, Lurie F, Gunther RA. Vet Anaesth Analg. 2006 Nov;33(6):368-80.
Effects of isovolemic resuscitation with hemoglobin-based oxygen carrier Hemoglobin glutamer-200 (bovine) on systemic and mesenteric perfusion and oxygenation in a canine model of hemorrhagic shock: a comparison with 6% hetastarch solution and shed blood.
Bonegio RG, Fuhro R, Ragno G, Robert Valeri C, Lieberthal W. Artif Cells Blood Substit Immobil Biotechnol. 2006;34(2):145-57.
A comparison of the acute hemodynamic and delayed effects of 50% exchange transfusion with two different cross-linked hemoglobin based oxygen carrying solutions and Pentastarch.
Ortegon DP, Davis MR, Sampson JB, Dick EJ, Kashyap V, Kerby JD. Microsurgery. 2006;26(3):203-6.
Bovine hemoglobin-based oxygen-carrying solution (HBOC-201) improves flap survival in a rat model of epigastric flap failure.
Buehler PW, Boykins RA, Jia Y, Norris S, Freedberg DI, Alayash AI. Anal Chem. 2005 Jun 1;77(11):3466-78.
Structural and functional characterization of glutaraldehyde-polymerized bovine hemoglobin and its isolated fractions.
Burmeister MA, Rempf C, Standl TG, Rehberg S, Bartsch-Zwemke S, Krause T, Tuszynski S, Gottschalk A, Schulte am Esch J. Br J Anaesth. 2005 Dec;95(6):737-45. Epub 2005 Oct 14.
Effects of prophylactic or therapeutic application of bovine haemoglobin HBOC-200 on ischaemia-reperfusion injury following acute coronary ligature in rats.
King DR, Cohn SM, Proctor KG. J Trauma. 2005 Sep;59(3):553-60; discussion 560-2.
Resuscitation with a hemoglobin-based oxygen carrier after traumatic brain injury.
Soma LR, Uboh CE, Guan F, Luo Y, Moate PJ, Boston RC, Driessen B. Anesth Analg. 2005 Jun;100(6):1570-5.
The pharmacokinetics of hemoglobin-based oxygen carrier hemoglobin glutamer-200 bovine in the horse.
Gasthuys M, Alves S, Tabet JC. Anal Chem. 2005 May 15;77(10):3372-8.
N-terminal adducts of bovine hemoglobin with glutaraldehyde in a hemoglobin-based oxygen carrier.
Gasthuys M, Alves S, Fenaille F, Tabet JC. Anal Chem. 2004 Nov 15;76(22):6628-34.
Simple identification of a cross-linked hemoglobin by tandem mass spectrometry in human serum.
Cheung AT, Driessen B, Jahr JS, Duong PL, Ramanujam S, Chen PC, Gunther RA. Artif Cells Blood Substit Immobil Biotechnol. 2004 May;32(2):189-207.
Blood substitute resuscitation as a treatment modality for moderate hypovolemia.
James MF, Potgieter HE, Ellis P. Anesth Analg. 2004 Dec;99(6):1593-7, table of contents.
The effect of hemopure on coagulation in clinically relevant concentrations.
Gurney J, Philbin N, Rice J, Arnaud F, Dong F, Wulster-Radcliffe M, Pearce LB, Kaplan L, McCarron R, Freilich D. J Trauma. 2004 Oct;57(4):726-38.
A hemoglobin based oxygen carrier, bovine polymerized hemoglobin (HBOC-201) versus Hetastarch (HEX) in an uncontrolled liver injury hemorrhagic shock swine model with delayed evacuation.
Fitzpatrick CM, Savage SA, Kerby JD, Clouse WD, Kashyap VS. J Am Coll Surg. 2004 Nov;199(5):693-701.
Resuscitation with a blood substitute causes vasoconstriction without nitric oxide scavenging in a model of arterial hemorrhage.
Callan MB, Rentko VT. Vet Clin North Am Small Anim Pract. 2003 Nov;33(6):1277-93, vi. Review.
Clinical application of a hemoglobin-based oxygen-carrying solution.
Strate T, Mann O, Kleinhans H, Schneider C, Knoefel WT, Yekebas E, Standl T, Bloechle C, Izbicki JR. Ann Surg. 2003 Nov;238(5):765-71.
Systemic intravenous infusion of bovine hemoglobin significantly reduces microcirculatory dysfunction in experimentally induced pancreatitis in the rat.
Posner LP, Moon PF, Bliss SP, Gleed RD, Erb HN. Vet Anaesth Analg. 2003 Jan;30(1):30-6.
Colloid osmotic pressure after hemorrhage and replenishment with Oxyglobin Solution, hetastarch, or whole blood in pregnant sheep.
Driessen B, Jahr JS, Lurie F, Golkaryeh MS, Gunther RA. Crit Care Med. 2003 Jun;31(6):1771-9.
Arterial oxygenation and oxygen delivery after hemoglobin-based oxygen carrier infusion in canine hypovolemic shock: a dose-response study.
Lurie F, Driessen B, Jahr JS, Reynoso R, Gunther RA. Anesth Analg. 2003 Jan;96(1):46-50, table of contents.
Validity of arterial and mixed venous oxygen saturation measurements in a canine hemorrhage model after resuscitation with varying concentrations of hemoglobin-based oxygen carrier.
Lurie F, Jahr JS, Driessen B. Am J Ther. 2002 Sep-Oct;9(5):425-30.
Changes in circulating blood and plasma volume after hemoglobin-based oxygen carrier infusion and additional infusion of colloid solutions.
Hohenhaus AE. J Vet Intern Med. 2002 Jul-Aug;16(4):394-5.
Oxyglobin: a transfusion solution?
Dorman SC, Kenny CF, Miller L, Hirsch RE, Harrington JP. Artif Cells Blood Substit Immobil Biotechnol. 2002 Jan;30(1):39-51.
Role of redox potential of hemoglobin-based oxygen carriers on methemoglobin reduction by plasma components.
Schutte AE. Ethics Med. 2002 Summer;18(2):55-62.
Ethical considerations concerning South Africa's approval of a blood substitute.
Ortegon DP, Davis MR, Dixon PS, Smith DL, Josephs JD, Mueller DL, Jenkins DH, Kerby JD. J Trauma. 2002 Dec;53(6):1068-72.
The polymerized bovine hemoglobin-based oxygen-carrying solution (HBOC-201) is not toxic to neural cells in culture.
Cheung AT, Jahr JS, Driessen B, Duong PL, Chan MS, Lurie F, Golkaryeh MS, Kullar RK, Gunther RA. Anesth Analg. 2001 Oct;93(4):832-8.
The effects of hemoglobin glutamer-200 (bovine) on the microcirculation in a canine hypovolemia model: a noninvasive computer-assisted intravital microscopy study.
Driessen B, Jahr JS, Lurie F, Gunther RA. J Vet Pharmacol Ther. 2001 Feb;24(1):61-71.
Inadequacy of low-volume resuscitation with hemoglobin-based oxygen carrier hemoglobin glutamer-200 (bovine) in canine hypovolemia.
Moon PF, Bliss SP, Posner LP, Erb HN, Nathanielsz PW. Vet Anaesth Analg. 2001 Apr;28(2):104-105. doi: 10.1046/j.1467-2987.2001.temp.doc.x-i10. Epub 2016 Nov 15.
Fetal oxygen content is restored with Oxyglobin resuscitation after maternal hemorrhage.
Posner LP, Moon PF, Bliss SP, Gleed RD, Erb HN. Vet Anaesth Analg. 2001 Apr;28(2):104. doi: 10.1046/j.1467-2987.2001.temp.doc.x-i9. Epub 2016 Nov 15.
Plasma colloid osmotic pressure after blood volume repletion with Oxyglobin, hetastarch, or whole blood in pregnant sheep.
Jahr JS, Lurie F, Xi S, Golkaryeh M, Kuznetsova O, Kullar R, Driessen B. Anesth Analg. 2001 Mar;92(3):609-14.
A novel approach to measuring circulating blood volume: the use of a hemoglobin-based oxygen carrier in a rabbit model.
Jahr JS, Lurie F, Driessen B, Tang Z, Louie RF, Kullar R, Kost G. Clin Lab Sci. 2000 Summer;13(2):173-9.
Validation of oxygen saturation measurements in a canine model of hemoglobin based oxygen carrier (HBOC) infusion.
Jahr JS, Lurie F, Gosselin R, Lin JS, Wong L, Larkin E. Clin Lab Sci. 2000 Fall;13(4):210-4.
Effects of a hemoglobin-based oxygen carrier (HBOC-201) on coagulation testing.
Roth RI, Levin J. N Engl J Med. 2000 Oct 26;343(17):1273.
Transfusion of soluble hemoglobin.
Standl T. Infusionsther Transfusionsmed. 2000 May;27(3):128-137.
Arificial Oxygen Carriers as Red Blood Cell Substitutes - Perfluorocarbons and Cell-Free Hemoglobin.
Mullon J, Giacoppe G, Clagett C, McCune D, Dillard T. N Engl J Med. 2000 Jun 1;342(22):1638-43.
Transfusions of polymerized bovine hemoglobin in a patient with severe autoimmune hemolytic anemia.
Braden TD, Tvedten HW, DeCamp CE, Turner TM, Hughes GS, Rentko VT. Am J Vet Res. 1999 Nov;60(11):1337-40.
Radiographic, biomechanical, and pathologic effects of hemoglobin glutamer-200 in dogs undergoing cemented total hip arthroplasty.
Hayward R, Lefer AM. Methods Find Exp Clin Pharmacol. 1999 Jul-Aug;21(6):427-33.
Administration of polymerized bovine hemoglobin improves survival in a rat model of traumatic shock.
Wolthuis A, Peek D, Scholten R, Moreira P, Gawryl M, Clark T, Westerhuis L. Clin Chem Lab Med. 1999 Jan;37(1):71-6.
Effect of the hemoglobin-based oxygen carrier HBOC-201 on laboratory instrumentation: cobas integra, chiron blood gas analyzer 840, Sysmex SE-9000 and BCT.
Kasper SM, Grüne F, Walter M, Amr N, Erasmi H, Buzello W. Anesth Analg. 1998 Aug;87(2):284-91.
The effects of increased doses of bovine hemoglobin on hemodynamics and oxygen transport in patients undergoing preoperative hemodilution for elective abdominal aortic surgery.
Brauer P, Standl T, Wilhelm S, Burmeister MA, Schulte am Esch J. J Neurosurg Anesthesiol. 1998 Jul;10(3):146-52.
Transcranial Doppler sonography mean flow velocity during infusion of ultrapurified bovine hemoglobin.
Caron A, Menu P, Labrude P, Vigneron C. Artif Cells Blood Substit Immobil Biotechnol. 1998 May;26(3):293-308.
Proposition of a technique to assess the vasoactive effects of hemoglobin-based oxygen carrying solutions in vivo: preliminary results in the rabbit aorta.
Standl T, Burmeister MA, Horn EP, Wilhelm S, Knoefel WT, Schulte am Esch J. Br J Anaesth. 1998 Feb;80(2):189-94.
Bovine haemoglobin-based oxygen carrier for patients undergoing haemodilution before liver resection.
Horn EP, Standl T, Wilhelm S, Jacobs EE, Freitag U, Freitag M, Schulte am Esch J. Anaesthesist. 1998 Feb;47(2):116-23. German.
[Bovine hemoglobin. HBOC-201 causes a reduction of the oxygen partial pressure in poststenotic skeletal muscle].
Standl T, Wilhelm S, Horn EP, Burmeister M, Gundlach M, Schulte am Esch J. Anaesthesist. 1997 Sep;46(9):763-70. German.
[Preoperative hemodilution with bovine hemoglobin. Acute hemodynamic effects in liver surgery patients ].
Sarkozi L, Jacobs E, Clark T, Gawryl MS, Simson E. Clin Chem. 1997 Sep;43(9):1792-4.
Effect of hemoglobin-based oxygen carrier-201 on common chemistry laboratory procedures.
Moreira PL, Lansden CC, Clark TL, Gawryl MS. Clin Chem. 1997 Sep;43(9):1792.
Effect of Hemopure on prothrombin time and activated partial thromboplastin time on seven coagulation analyzers.
Moreira PL, Lansden CC, Clark TL, Gawryl MS. Clin Chem. 1997 Sep;43(9):1790-1.
Effect of Hemopure on the performance of Ektachem and Hitachi clinical analyzers.
Callas DD, Clark TL, Moreira PL, Lansden C, Gawryl MS, Kahn S, Bermes EW Jr. Clin Chem. 1997 Sep;43(9):1744-8.
In vitro effects of a novel hemoglobin-based oxygen carrier on routine chemistry, therapeutic drug, coagulation, hematology, and blood bank assays.
Kasper SM, Walter M, Grüne F, Bischoff A, Erasmi H, Buzello W. Anesth Analg. 1996 Nov;83(5):921-7.
Effects of a hemoglobin-based oxygen carrier (HBOC-201) on hemodynamics and oxygen transport in patients undergoing preoperative hemodilution for elective abdominal aortic surgery.
Hughes GS, Francom SF, Antal EJ, Adams WJ, Locker PK, Yancey EP, Jacobs EE. Ann Emerg Med. 1996 Feb;27(2):164-9.
Effects of a novel hemoglobin-based oxygen carrier on percent oxygen saturation as determined with arterial blood gas analysis and pulse oximetry.
Hughes GS Jr, Francome SF, Antal EJ, Adams WJ, Locker PK, Yancey EP, Jacobs EE Jr. J Lab Clin Med. 1995 Nov;126(5):444-51.
Hematologic effects of a novel hemoglobin-based oxygen carrier in normal male and female subjects.
Hughes GS Jr, Yancey EP, Albrecht R, Locker PK, Francom SF, Orringer EP, Antal EJ, Jacobs EE Jr. Clin Pharmacol Ther. 1995 Oct;58(4):434-43.
Hemoglobin-based oxygen carrier preserves submaximal exercise capacity in humans.

News

April 18, 2019
Hemopure Plays A Pivotal Role in A Pioneering Study Published in Nature

Researchers from Yale School of Medicine Demonstrated Restored Cellular Functions In Pig Brains After Death Using Hemopure. Hemopure May Become a Novel, Broadly Applicable and Easy-to-Handle Perfusion Solution For Multiple Organs. SOUDERTON, Pa., April 18, 2019 /PRNewswire/ — Hemoglobin Oxygen Therapeutics LLC (HbO2 Therapeutics), a world leader in oxygen-carrying solutions, today announces pioneering research conducted…

April 9, 2019
Hemoglobin Oxygen Therapeutics LLC Announces Preclinical Results on Hemopure in Kidneys Discarded for Human Transplantation

Massachusetts General Hospital Study Suggest that Hemopure is an Acceptable Alternative for Human Blood Products in Kidneys Undergoing Machine Perfusion Technology. Study Published in The American Journal of Transplantation. SOUDERTON, PA, April 9, 2019 /PRNewswire/ — Hemoglobin Oxygen Therapeutics LLC ( HbO2Therapeutics), a biopharmaceutical company specializing in oxygen therapeutics, today announces the publication of preclinical data demonstrating that Hemopure…

February 13, 2019
Hemoglobin Oxygen Therapeutics LLC Announce Updated Results From The Netherlands Leading Liver Transplant Hospital

Pilot study shows ten donor livers previously rejected for transplant, salvaged with new machine perfusion technology using Company’s lead product, Hemopure®. To date, results show 100 percent transplant and survival rates for all patients. SOUDERTON, PA and GRONINGEN, The Netherlands. February 13 2019 —  Hemoglobin Oxygen Therapeutics LLC (HbO2 Therapeutics), a biopharmaceutical company specializing in oxygen…

January 21, 2019
Record number of liver transplants at UMCG due to new perfusion technique

​​In 2018, the UMCG carried out 73 liver transplants. On average around 60 liver transplants were done in the past few years, and in 2017 there were 56. This increase of around 20 percent is almost completely due to the use of normothermic machine preservation of donor livers that were rejected for transplantation in the…

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