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

Jiin Yu Chen, Michelle Scerbo, George Kramer

Research output: Contribution to journalArticle

99 Citations (Scopus)

Abstract

The complications associated with acquiring and storing whole blood for transfusions have launched substantial efforts to develop a blood substitute. The history of these efforts involves a complicated mixture of science, ethics, and business. This review focuses on clinical trials of the three hemoglobin-based oxygen carriers (HBOC) that have progressed to Phase II or III clinical trials: HemAssist (Baxter; Deerfield, IL, US), PolyHeme (Northfield; Evanston, IL, US), and Hemopure (Biopure; Cambridge, MA, US). Published animal studies and clinical trials carried out in a perioperative setting have demonstrated that these products successfully transport and deliver oxygen, but all may induce hypertension and lead to unexpectedly low cardiac outputs. Overall, these studies suggest that HBOCs resulted in only modest blood saving during and after surgery, no improvement in mortality and an increased incidence of adverse reactions. To date, the results from these perioperative studies have not led to regulatory approval. All three companies instead chose to focus their efforts on large trials of trauma patients in the pre-hospital setting. Baxter abandoned the development of HemAssist after a trial in the U.S. was prematurely halted when the first 100 patients showed significantly increased mortality rates as compared to patients treated with blood products. Northfield's PolyHeme trial demonstrated a non-significant trend towards increased mortality and a very modest reduction in the subsequent need for blood. The testing of Biopure's Hemopure for trauma patients has been halted for several years because of FDA concerns over trial design and study justification. Ethical concerns have also been raised regarding the design and implementation of all HBOC clinical trials. Thus, the available evidence suggests that HemAssist, Polyheme, and Hemopure are associated with a significant level of cardiovascular dysfunction. The next generation of HBOCs remains under development.

Original languageEnglish (US)
Pages (from-to)803-813
Number of pages11
JournalClinics
Volume64
Issue number8
DOIs
StatePublished - 2009

Fingerprint

Clinical Ethics
Blood Substitutes
Hemoglobins
History
Clinical Trials
Oxygen
Mortality
Business Ethics
Low Cardiac Output
Phase III Clinical Trials
Phase II Clinical Trials
Wounds and Injuries
Blood Transfusion
Hypertension
Incidence
HBOC 201
PolyHeme

Keywords

  • Blood substitute
  • HBOC
  • HemAssist
  • Hemopure
  • PolyHeme

ASJC Scopus subject areas

  • Medicine(all)

Cite this

A review of blood substitutes : Examining the history, clinical trial results, and ethics of hemoglobin-based oxygen carriers. / Chen, Jiin Yu; Scerbo, Michelle; Kramer, George.

In: Clinics, Vol. 64, No. 8, 2009, p. 803-813.

Research output: Contribution to journalArticle

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