Hemoglobin substitutes

  • Kevin K. Anbari
  • Jonathan P. Garino
  • Colin F. Mackenzie


Orthopaedic patients frequently require blood transfusions to treat peri-operative anemia. Research in the area of hemoglobin substitutes has been of great interest since it holds the promise of reducing the reliance on allogeneic blood transfusions. The three categories of hemoglobin substitutes are (1) cell-free, extracellular hemoglobin preparations made from human or bovine hemoglobin (hemoglobin-based oxygen carriers or HBOCs); (2) fluorinesubstituted linear or cyclic carbon chains with a high oxygen-carrying capacity (perfluorocarbons); and (3) liposome-encapsulated hemoglobin. Of the three, HBOCs have been the most extensively studied and tested in preclinical and clinical trials that have shown success in diminishing the number of blood transfusions as well as an overall favorable side-effect profile. This has been demonstrated in vascular, cardiothoracic, and orthopaedic patients. HBOC- 201, which is a preparation of cellfree bovine hemoglobin, has been approved for clinical use in South Africa. These products may well become an important tool for physicians treating peri-operative anemia in orthopaedic patients.


Hemoglobin substitute HBOC HBOC-201 Perfluorocarbons 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Aguzzi A, Glatzel M (2004) vCJD tissue distribution and transmission by transfusion — a worst-case scenario coming true? Lancet 363:411–412CrossRefPubMedGoogle Scholar
  2. 2.
    Ania BJ, Suman VJ, Fairbanks VF, Rademacher DM, Melton LJ 3rd (1997) Incidence of anemia in older people: an epidemiologic study in a well defined population. J Am Geriatr Soc 45:825–831PubMedGoogle Scholar
  3. 3.
    Bierbaum BE, Callaghan JJ, Galante JO, Rubash HE, Tooms RE, Welch RB (1999) An analysis of blood management in patients having a total hip or knee arthroplasty. J Bone Joint Surg Am 81:2–10PubMedGoogle Scholar
  4. 4.
    Chatterjee R, Welty EV, Walder RY, Pruitt SL, Rogers PH, Arnone A, Walder JA (1986) Isolation and characterization of a new hemoglobin derivative crosslinked between the alpha chains (lysine 99 alpha 1-lysine 99 alpha 2). J Biol Chem 261:9929–9937PubMedGoogle Scholar
  5. 5.
    Conover CD, Malatesta P, Lejeune L, Chang CL, Shorr RG (1996) The effects of hemodilution with polyethylene glycol bovine hemoglobin (PEG-Hb) in a conscious porcine model. J Investig Med 44:238–246PubMedGoogle Scholar
  6. 6.
    Goodnough LT, Brecher ME, Kanter MH, AuBuchon JP (1999) Transfusion medicine: first of two parts. N Engl J Med 340:438–447CrossRefPubMedGoogle Scholar
  7. 7.
    Greer JP, Foerster J, Lukens JN (eds) (2003) Transfusion medicine. In: Wintrobe’s clinical hematology. Lippincott, PhiladelphiaGoogle Scholar
  8. 8.
    Guyton AC (2000) Red blood cells, anemia, and polycythemia. In: Textbook of medical physiology, 10th edn. WB Saunders, PhiladelphiaGoogle Scholar
  9. 9.
    Hughes GS Jr, Antal EF, Locker PK, Francom SF, Adams WJ, Jacobs EE Jr (1996) Physiology and pharmacokinetics of a novel hemoglobin-based oxygen carrier in humans. Crit Care Med 24:756–764CrossRefPubMedGoogle Scholar
  10. 10.
    Jahr JS, Stewart LM, MacKenzie C, Bourke DL, Williams JP (2002) Pivotal phase III study: safety of polymerized bovine hemoglobin (HBOC-201, Hemopure) as compared to RBC in patients undergoing orthopaedic surgery. Anesthesiology Supplement] 97:A243Google Scholar
  11. 11.
    Janatpour K, Holland PV (2002) Noninfectious serious hazards of transfusion. Curr Hematol Rep 1:149–155PubMedGoogle Scholar
  12. 12.
    Keating EM (1999) Current options and approaches for blood management in orthopaedic surgery. Instr Course Lect 48:655–665PubMedGoogle Scholar
  13. 13.
    Keating EM, Meding JB (2002) Perioperative blood management practices in elective orthopaedic surgery. J Am Acad Orthop Surg 10:393–400PubMedGoogle Scholar
  14. 14.
    Kopko PM, Marshall CS, MacKenzie MR, Holland PV, Popovsky MA (2002) Transfusion-related acute lung injury: report of a clinical look-back investigation. JAMA 287:1968–1971CrossRefPubMedGoogle Scholar
  15. 15.
    LaMuraglia GM, O’Hara PJ, Baker WH, Naslund TC, Norris EJ, Li J, Vandermeersch E (2000) The reduction of the allogenic transfusion requirement in aortic surgery with a hemoglobin-based solution J Vasc Surg 31: 299–308CrossRefPubMedGoogle Scholar
  16. 16.
    Levy JH, Goodnough LT, Greilich PE, Parr GVS, Stewart RW, Gratz I, Wahr J, Williams J, Comunale ME, Doblar D, Silvay G, Cohen M, Jahr JS, Vlahakes GJ (2002) 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 Cardiovasc Surg 124:35–42CrossRefPubMedGoogle Scholar
  17. 17.
    Llewelyn CA, Hewitt PE, Knight RSG, Amar K, Cousens S, Mackenzie J, Will RG (2004) Possible transmission of variant Creutzfeldt-Jakob disease by blood transfusion. Lancet 363:417–421PubMedGoogle Scholar
  18. 18.
    Menitove JE (2000) Transfusion-transmitted diseases. In: Hoffman R (ed) ematology: basic principles and practice, 3rd edn. Churchill Livingstone, New YorkGoogle Scholar
  19. 19.
    Moore EE (2003) Blood substitutes: The future is now. J Am Coll Surg 196:1–17CrossRefPubMedGoogle Scholar
  20. 20.
    Sampson JB, Davis MR, Mueller DL, Kashyap VS, Jenkins DH, Kerby JD (2003) A comparison of the hemoglobin-based oxygen carrier HBOC-201 to other low-volume resuscitation fluids in a model of controlled hemorrhagic shock. J Trauma 55:747–754PubMedGoogle Scholar
  21. 21.
    Spahn DR, Waschke KF, Standl T, Motsch J, Van Huynegem L, Welte M, Gombotz H, Coriat P, Verkh L, Faithfull S, Keipert P (2002) Use of Perflubron emulsion to decrease allogeneic blood transfusion in high-bloodloss non-cardiac surgery: results of a European phase 3 study. Anesthesiology 97:1338–1349PubMedGoogle Scholar
  22. 22.
    Standl T, Freitag M, Burmeister MA, Horn PE, Wilhelm S, Schulte am Esch J (2003) Hemoglobin-based oxygen carrier HBOC-201 provides higher and faster increase in oxygen tension in skeletal muscle of anemic dogs than do stored red blood cells. J Vasc Surg 37: 859–865CrossRefPubMedGoogle Scholar
  23. 23.
    Standl T, Horn P, Wilhelm S, Greim C, Freitag M, Freitag U, Sputtek A, Jacobs E, Schulte am Esch J (1996) Bovine hemoglobin is more potent than autologous red blood cells in restoring muscular tissue oxygenation after profound isovolaemic haemodilution in dogs. Can J Anaesth 43:714–723PubMedGoogle Scholar
  24. 24.
    Stowell CP, Levin J, Speiss BD, Winslow RM (2001) Progress in the development of RBC substitutes. Transfusion 41:287–299CrossRefPubMedGoogle Scholar
  25. 25.
    Swanson ME, Martin MJ, O’Donnell JK, Hoover K, Lago W, Huntress V, Parsons CT, Pinkert CA, Pilder S, Logan JS (1992) Production of functional human hemoglobin in transgenic swine. BioTechnology 10:557–559CrossRefPubMedGoogle Scholar
  26. 26.
    Tremper KK (2002) Perfluorochemical “red blood cell substitutes”: the continued search for an indication. Anesthesiology 97:1333–1334CrossRefPubMedGoogle Scholar
  27. 27.
    Winslow RM (2000) Red cell substitutes. In: Hoffman R (ed) Hematology: basic principles and practice, 3rd edn. Churchill Livingstone, New YorkGoogle Scholar
  28. 28.
    York GB, Eggers JS, Smith DL, Jenkins DH, McNeil JD, Mueller D, Josephs JD, Kerby JD (2003) Low-volume resuscitation with a polymerized bovine hemoglobin-based oxygen-carrying solution (HBOC-201) provides adequate tissue oxygenation for survival in a porcine model of controlled hemorrhage. J Trauma 55:873–885PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2005

Authors and Affiliations

  • Kevin K. Anbari
    • 1
  • Jonathan P. Garino
    • 1
    • 2
  • Colin F. Mackenzie
    • 3
  1. 1.Department of Orthopaedic SurgeryUniversity of Pennsylvania Health SystemPhiladelphiaUSA
  2. 2.Department of Orthopaedic Surgery, 1 Cupp PavilionPresbyterian HospitalPhiladelphiaUSA
  3. 3.Department of AnesthesiologyUniversity of Maryland School of MedicineBaltimoreUSA

Personalised recommendations