A review of blood substitutes: Examining the history, clinical trial results, and ethics of hemoglobin-based oxygen carriers

Clinics

Volumn 64, Issue 8, 2009, Pages 803-813

  Chen, Jiin Yu ^a   Scerbo, Michelle ^a   Kramer, George ^a  

^a University of Texas Medical Branch School of Medicine   (United States)

Author keywords

Blood substitute; HBOC; HemAssist; Hemopure; PolyHeme

Indexed keywords

BLOOD SUBSTITUTE; HEMOGLOBIN; POLYMERIZED HEMOGLOBIN;

CLASSIFICATION; CLINICAL TRIAL; ETHICS; HUMAN; REVIEW;

BLOOD SUBSTITUTES; CLINICAL TRIALS AS TOPIC; HEMOGLOBINS; HUMANS;

EID: 70349623928     PISSN: 18075932     EISSN: None     Source Type: Journal    
DOI: 10.1590/S1807-59322009000800016     Document Type: Review

References (51)

1. McCullough J. Progress toward a pathogen-free blood supply. Clin Infect Dis. 2003;37:88-95.
2. Ross S, Jeter E. Emergency surgery, trauma, and massive transfusion. In: Petz LD, Kleinmann S, Swisher SN, Spence RK, Strauss RG, eds. Clinical Practice of Transfusion Medicine. 3rd ed. New York: Churchill Livingstone; 1996. p.563-79.
3. Dunne JR, Malone DL, Tracy JK, Napolitano LM. Allogeneic blood transfusion in the first 24 hours after trauma is associated with increased systemic inflammatory response system (SIRS) and death. Surgical Infections. 2004;5:395-404.
4. Moore FA, Moore EE, Sauaia A. Blood transfusion: An independent risk factor for post injury multiple organ failure. Arch Surg. 1997;132:620-25.
5. Thomas TG. The intravenous injection of milk as a substitute for the transfusion of blood. NY State J Med. 1878;47:449-65.
6. Amberson WR, Mulder AG, Steggerda FR, Flexner J, Pankratz DS. Mammalian life without red blood corpuscles. Science. 1933;78:106-7.
7. Amberson WR, Jennings JJ, Rhode CM. Clinical experience with hemoglobin-saline solutions. J Appl Physiol. 1949;1:469-89.
8. Winslow RM. The results of 62 large-volume hemoglobin infusions in man. Hemoglobin-Based Red Cell Substitutes. Baltimore and London: Johns Hopkins University Press 1992:177-8.
9. Bunn H, Jandl J. The renal handling of hemoglobin. Transactions of the Association of American Physicians. 1968;81:147-52.
10. Winslow RM. αα-Crosslinked hemoglobin. In: Winslow RM, editor. Blood Substitutes. London: Academic Press 2006. p.386-98.
11. Winslow RM. Hemoglobin modification. In: Winslow RM, editor. Blood Substitutes. London: Academic Press 2006. p.341-53.
12. Bonsen P, Laver M, Morris K, inventors; Alza Corporation, assignee. Novel polymerized, cross-linked, stroma-free hemoglobin. United States. 1975.
13. Tam S, Blumenstein J, Wong J. Soluble dextran-hemoglobin complex as a potential blood substitute (plasma expander/oxygen binding/covalent coupling). Proc Natl Acad Sci USA. 1976;73:2128-31.
14. Humphries RG, Killingback PG, Mann J, Sempik J, Wilson J. Exchange transfusion with dextran-hemoglobin, hemoglobin and dextran solutions in anaesthetized cats. Br J Pharmacol. 1980.74:266.
15. Lamy ML, Daily EK, Brichant JF, Larbuisson RP, Demeyere RJ, Vandermeersch EA, et al. Randomized trial of Diaspirin Cross-Linked hemoglobin solution as an alternative to blood transfusion after cardiac surgery. Anesthesiology. 2000;92:646-56.
16. Nolte D, Steinhauser P, Pickelmann S, Berger S, Härtl R, Messmer K. Effects of Diaspirin-Cross-Linked hemoglobin (DCLHb) on local tissue oxygen tension in striated skin muscle: An efficacy study in the hamster. J Lab Clin Med. 1997;138:328-38.
17. Northfield. Potential battle field use [Online]. 2006. [cited 2007 April 26] Available from: http://www.northfieldlabs.com/us_army.html
18. Handrigan MT, Bentley TB, Oliver JD, Tabaku L, Buge J, Atkins J. Choice of fluid influences outcome in prolonged hypotensive resuscitation after hemorrhage in awake rats. Shock. 2005;23:337-43.
19. Dubick MA, Sondeen JL, Prince MD, James AG, Nelson JJ, Hernandez EL. Hypotensive resuscitation with Hextend, Hespan or PolyHeme in a swine hemorrhage model. Shock. 2004;21 (Suppl 2):42. (abstract)
20. Johnson JL, Moore EE, Offner PJ, Haenel JB, Hides GA, Tamura DY. Resuscitation of the injured patient with polymerized stroma-free hemoglobin does not produce systemic or pulmonary hypertension. Am J Surg. 1998;176:612-7.
21. Gould SA, Sehgal LR, Sehgal HL, Moss GS. The development of hemoglobin solutions as red cell substitutes: Hemoglobin solutions. Transfusion Science. 1995;16:5-17.
22. Thompson A, McGarry AE, Valeri R, Liberthal W. Stroma-free hemoglobin increases blood pressure and GFR in the hypotensive rate: role of nitric oxide. J Appl Physiol. 1994;77:2348-54.
23. Gould SA, Moore EE, Hoyt DB, Burch JM, Haenel J, Garcia J, et al. The first randomized trial of human polymerized hemoglobin as a blood substitute in acute trauma and emergent surgery. Journal of the American College of Surgeons. 1998;187:113-20.
24. Northfield. Northfield Laboratories reports preliminary top-line data in pivotal Phase III trauma study [press release]. [Online] Evanston, IL: Business Wire; [updated 2006 December 16; cited 2007 April 26]. Available from: http://phx.corporate-ir.net/phoenix.zhtml?c=91374&p=irolnewsArticle&ID=943580&highlight=
25. Northfield. Northfield Laboratories reports results of pivotal Phase III trauma study [press release]. [Online] Evanston, IL: Business Wire; [updated 2007 May 23; cited 2007 June 14]. Available from: http://phx.corporate-ir.net/phoenix.zhtml?c=91374&p=irol-newsArticle&ID=1005951&highlight=
26. Rentko VT, Pearce LB, Moon-Massat PF, Gawryl MS. Hemopure (HBOC-201, Hemoglobin Glutamer-250 (Bovine)): preclinical studies. In: Winslow RM, editor. Blood Substitutes. London: Academic Press 2006. p.424-36.
27. Pearce BL, Gawryl MS, Rentko VT. HBOC-201(Hemoglobin Glutamer-250 (Bovine),Hemopure): Clinical Studies. In: Winslow, RM, editor. Blood Substitutes. London: Academic Press; 2006. p.437-50.
28. Biopure Corporation. Biopure announces 2007 third quarter financial results [press release]. [Online]. Cambridge, MA: PRNewswire-FirstCall; [updated 2007 August 23; cited 2008 May 7]. Available from: http://www.bio-medicine.org/medicine-technology-1/biopure-announces-2007-third-quarter-financial-results-129-1/
29. Saxena R, Wijnhoud A, Carton H, Hacke W, Kaste M, Przybelski R, et al. Controlled safety study of a hemoglobin-based oxygen carrier, DCLHb, in acute ischemic stroke. Stroke. 1999;30:993-96. Stroke. 1999;30:993-96.
30. Schubert A, Przybelski RJ, Eidt JF, Lasky LC, Marks KE, Karafa M, et al. Diaspirin-Crosslinked hemoglobin reduces blood transfusion in noncardiac surgery: A multicenter, randomized controlled, double-blinded trial. Anesth Analg. 2003;7:323-32.
31. University of Illinois at Chicago. U.S. trauma study design [Online]. 1998 [cited 2007 April 27]; Available from: http://web.archive.org/web/19990302030029/dclhb.er.uic.edu/ustrauma.htm
32. Sloan EP, Koenigsberg M, Gens D, Cipolie M, Runge J, Mallory MN, et al. Diaspirin cross-linked hemoglobin (DCLHb) in the treatment of severe traumatic hemorrhage shock: A randomized controlled efficacy trial. JAMA. 1999;282(19):1857-64.
33. Baxter Healthcare Corporation. Baxter ends U.S. trauma study of HemAssist (DCLHb); European trauma and U.S. surgery trials continue on track [press release]. [Online]. Deerfield, IL: PRNewswire; [updated, 1988 March 31; cited 2007 April 27]. Available from: http://web.archive.org/web/19981205122026/dclhb.er.uic.edu/press_release.htm
34. Kerner T, Ahlers O, Veit S, Riou B, Saunders M, Pison U. DCLHb for trauma patients with severe hemorrhagic shock: The European "onscene" multicenter study. Intensive Care Med. 2003;29:347-49.
35. Gould SA, Moore EE, Hoyt DB, Ness PM, Norris EJ, Carson JL, et al. The life-sustaining capacity of human polymerized hemoglobin when red cells might be unavailable. Journal of the American College of Surgeons. 2002;195:445-52.
36. Kasper SM, Walter M, Grüne F, Bischoff A, Erasmi H, Buzello W. Effects of hemoglobin-based oxygen carrier (HBOC-201) on hemodynamics and oxygen transport in patients undergoing preoperative hemodilution for elective abdominal aortic surgery. Anesth Analg. 1996;83:912-27.
37. Bloomfield EL, Rady MY, Esfandiari S. A prospective trial of diaspirin-cross linked hemoglobin solution in patients after elective repair of abdominal aortic aneurysm. Mil Med. 2004;169:546-50.
38. LaMuraglia G, O'Hara PJ, Baker WH, Naslund TC, Norris EJ, Li J, et al. The reduction of the allogenic transfusion requirement in aortic surgery with a hemoglobin-based solution. J Vasc Surg. 2000;31:299-308.
39. Levy JH, Goodnough LT, Greilich PE, Parr GS, Stewart RW, Gratz I, et al. Polymerized bovine hemoglobin solution as a replacement for allogeneic red blood cell transfusion after cardiac surgery: Results of a randomized, double-blind trial. J Thorac Cardiovas Surg. 2002;124:35-42.
40. Sprung J, Kindscher JD, Waher JA, Levy JH, Monk TG, Moritz MW, et al. The use of bovine hemoglobin glutamer-250 (Hemopure) in surgical patients: Results of a multicenter, randomized, single-blinded trial. Anesth Analg. 2002;94:799-808.
41. Biopure Corporation. FDA panel recommends Navy's proposed 'RESUS' Phase IIb/III trauma trial not proceed as designed; suggests phase II study [press release]. [Online]. Cambridge, MA: PRNewswire-FirstCall;[updated 2006 December 15; cited 2007 April 26]. Available from: http://www.corporateir.net/ireye/ir_site.zhtml?ticker=bpur&script=419&layout=0&item_id=942537
42. Jahr JS, Mackenzie C, Pearce LB, Pitman A, Greenburg AG. HBOC-201 as an Alternative to Blood Transfusion: Efficacy and Safety Evaluation in a Multicenter Phase III Trial in Elective Orthopedic Surgery. J Trauma. 2008;64:1484-97.
43. Orfinger B. South Africa approves first blood substitute. [Online] 2001. [cited 2007 April 25]. Available from: http://www.redcross.org/news/bm/intl/010419sub.html
44. [Food and Drug Administration. Part 50- Protection of human subjects Subpart B- informed consent of human subjects Sec 50.24 Exception from informed consent requirements for emergency research [Online]. 1996 [cited 2007 April 26] Available from: http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=50.2
45. Guterman L. Guinea pigs in the ER: Researchers debate the ethics and logistics of performing emergency research without patients' consent. The Chronicle of Higher Education. 2006;52:A14-8.
46. Kipnis K, King NP, Nelson RM. An open letter to IRBs considering Northfield Laboratories' PolyHeme trial. The American Journal of Bioethics. 2006;6:18-21.
47. Natanson C, Kern SJ, Lurie P, Banks SM, Wolfe SM. Cell-Free Hemoglobin-Based Blood Substitutes and Risk of Myocardial Infarction and Death: A Meta-analysis. JAMA. 2008;299:2304-12.
48. Biopure. Scientific Commentary on the Natanson et al. Meta-analysis. [Online] 2008 [cited 2008 October 16]; Available from: http://www.biopure.com/jamacomments.php
49. HemoBioTech. Our product-clinical testing. [Online] 2006 [cited 2008 May 6]; Available from: http://hemobiotech.com/product/clinicalresearch.php
50. Sangart. Hemospan: Product information. [Online] 2007. [cited 2008 May 6]. Available from: http://www.sangart.com/hemospan/product-info.php
51. Oxygenix. Oxy-0301- oxygen carrier. [Online] 2006. [cited 2008 May 6]. Available from: http://www.oxy-genix.com/english/kenkyu/jinko.html