BLOOD SUBSTITUTES

Why an alternative to blood transfusion?Crit Care Clin. 2009 Apr;25(2):261-77.

Human polymerized hemoglobin for the treatment of hemorrhagic shock when blood is unavailable: the USA multicenter trial. J Am Coll Surg. 2009 Jan;208(1):1-13. Epub 2008 Nov 7. Patients resuscitated with PolyHeme, without stored blood for up to 6 U in 12 hours postinjury, had outcomes comparable with those for the standard of care. Although there were more adverse events in the PolyHeme group, the benefit-to-risk ratio of PolyHeme is favorable when blood is needed but not available.

PolyHeme: are we ready for a blood substitute? Mo Med. 2009 Jan-Feb;106(1):74-7.One potential blood substitute, PolyHeme has recently completed a Phase III clinical trial. The scientific foundations for the use of the product are described in this review as are some of the preliminary results and controversies. Ultimately, the role of PolyHeme will depend in a great deal on review of the results of the current study.

Artificial Oxygen Carriers, Hemoglobin Vesicles and Albumin-Hemes, Based on Bioconjugate Chemistry. Bioconjug Chem. 2009 Feb 10. [Epub ahead of print]. Hemoglobin (Hb, Mw: 64 500) and albumin (Mw: 66 500) are major protein components in our circulatory system. On the basis of bioconjugate chemistry of these proteins, we have synthesized artificial O(2) carriers of two types, which will be useful as transfusion alternatives in clinical situations. Along with sufficient O(2) transporting capability, they show no pathogen, no blood type antigen, biocompatibility, stability, capability for long-term storage, and prompt degradation in vivo.

HBOC-201 Vasoactivity in a Phase III Clinical Trial in Orthopedic Surgery Subjects-Extrapolation of Potential Risk for Acute Trauma Trials. J Trauma. 2009 Feb;66(2):365-376.Our limited HEM-0115 safety analysis shows that key potentially vasoactivity-related adverse safety signals were more frequent with HBOC-201 than RBC in older patients undergoing orthopedic surgery with rapid access to safe blood transfusions. That incidences of these safety signals were generally lower and group differences narrowed in subpopulations with stable trauma, hypotension, and younger age, suggests an acceptable safety profile in younger acute trauma populations, especially in settings where rapid access to safe blood transfusions is unavailable; confirmation in controlled clinical trials is urgently warranted.

Prevention of the Pulmonary Vasoconstrictor Effects of HBOC-201 in Awake Lambs by Continuously Breathing Nitric Oxide. Anesthesiology. 2009 Jan;110(1):113-122. Pretreatment with inhaled nitric oxide followed by breathing a lower concentration of the gas during and after administration of HBOC-201 may enable administration of an acellular hemoglobin substitute without vasoconstriction while preserving its oxygen-carrying capacity.

Ex vivo generation of human red blood cells: a new advance in stem cell engineering. Methods Mol Biol. 2009;482:127-40. The RBC generated in vitro have all the characteristics of functional native adult RBC.

Effects of different resuscitation fluids on the rheologic behavior of red blood cells, blood viscosity and plasma viscosity in experimental hemorrhagic shock. Resuscitation. 2008 Dec 5. [Epub ahead of print]. These results suggested that at the early stage of hemorrhagic shock resuscitation, hypertonic-hyperoncotic resuscitation could improve RBC deformability compared with isotonic crystalloid resuscitation. Dextran 70 could elevate plasma viscosity to nearly baseline level. These effects of hypertonic-hyperoncotic resuscitation could be beneficial to maintain microcirculation.

Blood transfusion research prompts search for artificial substitutes Telegraph.co.uk Last Updated: 8:01pm BST 13/10/2008

HBOC-201, hemoglobin glutamer-250 (bovine), Hemopure (Biopure Corporation).

Expert Opin Biol Ther. 2008 Sep;8(9):1425-33.While HBOC-201 may not replace allogenic blood transfusions, it may serve to allow critically ill patients to be resuscitated in the field or hospital setting until either regeneration of red cell occurs or a transfusion is available.

Liposome-encapsulated hemoglobin transfusion rescues rats undergoing progressive hemodilution from lethal organ hypoxia without scavenging nitric oxide.

Ann Surg. 2008 Aug;248(2):310-9. Liposome-encapsulated hemoglobin is effective in rescuing rats undergoing progressive hemodilution from lethal organ hypoxia without scavenging NO.

Balance between vasoconstriction and enhanced oxygen delivery.

Transfusion. 2008 Jun 27. [Epub ahead of print] Further studies to establish acellular Hb optimal dosage, efficacy, safety, and effects on outcome are indicated before these solutions are implemented in routine practice.

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 Jun;64(6):1484-97. HBOC-201 eliminated transfusion in the majority of subjects. The between arms (H vs. R) safety analysis was unfavorable and likely related to patient age, volume overload, and undertreatment and was isolated to patients that could not be managed by HBOC-201 alone. However, patients <80 years old with moderate clinical need may safely avoid transfusion when treated with up to 10 units of HBOC-201.

Haemoglobin, oxygen carriers and perioperative organ perfusion.Best Pract Res Clin Anaesthesiol. 2008 Mar;22(1):63-80. Review

Inhaled nitric oxide enables artificial blood transfusion without hypertension.

Circulation. 2008 Apr 15;117(15):1982-90. Epub 2008 Apr 7. HBOC can cause systemic vasoconstriction by scavenging NO produced by NOS3. Moreover, in 2 species, inhaled NO administered before the intravenous infusion of HBOC can prevent systemic vasoconstriction without causing methemoglobinemia.

Inhaled Nitric Oxide Enables Artificial Blood Transfusion Without Hypertension.

Circulation. 2008 Apr 7; [Epub ahead of print] HBOC can cause systemic vasoconstriction by scavenging NO produced by NOS3. Moreover, in 2 species, inhaled NO administered before the intravenous infusion of HBOC can prevent systemic vasoconstriction without causing methemoglobinemia.

Basic science focus on blood substitutes: a summary of the NHLBI Division of Blood Diseases and Resources Working Group Workshop, March 1, 2006.

Transfusion. 2008 Jan 7; [Epub ahead of print] This communication summarizes the opinion of workshop participants on these issues and concludes with a list of specific recommended areas of research that could positively impact the development of blood substitutes.

Haemoglobin-vesicles as artificial oxygen carriers: present situation and future visions.

J Intern Med. 2007 Nov 27; [Epub ahead of print] Review

Resuscitation From Hemorrhagic Shock Comparing Standard Hemoglobin-Based Oxygen Carrier (HBOC)-201 Versus 7.5% Hypertonic HBOC-201.

Trans-sodium crocetinate and hemorrhagic shock.
Shock. 2007 May 31; [Epub ahead of print]. Trans-sodium crocetinate clearly holds promise as a useful treatment of hemorrhagic shock.

The Novel Hemoglobin-based Oxygen Carrier HRC 101 Improves Survival in Murine Sickle Cell Disease.
Anesthesiology. 2007 Aug;107(2):281-287. Experrimental study.

Ex vivo Production of Human Red Blood Cells From Hematopoietic Stem Cells: What Is the Future in Transfusion?
Transfus Med Rev. 2007 Apr;21(2):91-100. The Authors describe in this article a methodology permitting the massive ex vivo production of mature human RBCs having all the characteristics of native adult RBCs from hematopoietic stem cells of diverse origins: blood, bone marrow, or cord blood. This protocol allows both the massive expansion of hematopoietic stem cells/progenitors and their complete differentiation to the stage of perfectly functional mature RBCs. The levels of amplification obtained (10(5) to 2 x 10(6)) are compatible with an eventual transfusion application.

Resuscitation following severe, controlled hemorrhage associated with a 24h delay to surgical intervention in swine using a hemoglobin based oxygen carrier as an oxygen bridge to definitive care.
Resuscitation. 2007 Mar 22; [Epub ahead of print] HBOC-201 restored hemodynamics, maintained tissue oxygenation, and decreased blood transfusions in comparison to HEX in severe controlled HS with 24h delay to simulated hospital care. These results support the potential use of HBOC-201 as a bridging resuscitation fluid for HS.