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Medical Meeting Reports

American College of Surgery Clinical Congress

October 10-15, 1999


CLINICAL USES OF BLOOD SUBSTITUTES IN SURGERY
font=>By Kevin Boyd

David Hoyt, MD, of the University of California, San Diego reviewed the blood substitutes currently in development, and concluded that polymerized hemoglobin products have the greatest likelihood of success.

Need for Blood Substitutes

The need for blood substitutes that can efficiently deliver oxygen continues to be strong, Hoyt said. While the risk of viral infection from a blood transfusion has dropped significantly in recent years (for example, HIV infection incidence has declined from 1 in 225,000 to 1 in 439,000), the risk still exists. Blood substitutes may also help to avoid problems precipitated by stored red cells, such as inflammatory responses and tissue damage mediated via neutrophils (PMNs). Blood substitutes may be particularly useful in some trauma room procedures where the need for especially large amounts of blood outstrips stored blood capacity.

Advantage of Polymerized Hemoglobin Blood Substitutes

Dr Hoyt noted that polymerized hemoglobin blood substitutes have the advantage of maintaining the hemoglobin molecule's function while preventing the smaller hemoglobin dimers from scavenging NO, a mechanism that leads to vasoconstriction and hypertension. Dr. Hoyt mentioned 3 polymerized products: Northfield's Polyheme, a polymerized human hemoglobin that has entered into phase 3 trials in which patients safely have been given up to 10 units in 20 minutes during trauma situations; Biopure's Hemopure, a bovine hemoglobin product that has entered phase 2 trials with no apparent toxicity or immunity problems; and Hemosol's Hemolink, a hemoglobin that is crosslinked both intra- and inter-molecularly and has entered phase three trials in Canada.

Other products that have shown promise during development an early clinical trials include hemoglobin conjugated to polyethylene-based polymer (variants are made by Enzon and Apex), and recombinant hemoglobin (produced by Somatogen).

No Activation of Vascular Endothelial Cells

Junichi Aiboshi, MD of Denver Health Medical Center, presented a paper in the surgical forum that demonstrated one advantage of blood substitutes - that they do not lead to activation of vascular endothelial cells.

Previous studies have shown that packed red blood cells contain cytokines and lipids that can prime PMNs. Beta-2-integrins on the surface of PMNs can interact with ICAM-1 on the surface of vascular endothelial cells. This interaction has been implicated in PMN-mediated tissue injury, which may lead to multiple organ failure.

Aiboshi and his colleagues mixed human microvascular endothelial cells together with varying concentrations of either plasma from packed red blood cells or the polymerized hemoglobin Polyheme, and after 6 hours measured ICAM-1 expression by flow cytometry.

Plasma from red blood cells significantly increased surface ICAM-1 expression at each concentration compared with untreated control cells (mean fluorescence intensity 8.01 to 8.69 compared with 4.5). Polyheme did not induce significant increases in ICAM-1 expression. This suggested that Polyheme can be used for acute resuscitation without destructive activation of vascular endothelial cells and PMN priming. Such treatment might prevent postinjury multiple organ failure.

For professional correspondence, please contact Dr. Hoyt at dhoyt@ucsd.edu

Ortho Biotech

Funded through an unrestricted educational grant by Ortho Biotech.



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