Possible Role of Artificial Oxygen Carriers in Transfusion Medicine: A Retrospective Analysis on the Current Transfusion Practice

Abstract

Artificial oxygen carriers (AOC) are under development as a substitute for red blood cells (RBC) in homologous transfusion (Tx). The lack of surface antigen in AOC makes ABO-typing and antibody-screening (T/S) unnecessary. Pathogen elimination renders it much safer, and long-term stability allows ubiquitous storage for emergency use. To delineate the utility of AOC, we retrospectively examined current Tx practices in Tokai University and the Japanese Red Cross Society. The emergency department of Tokai University Hospital has been using O(+)Rh(+) RBC in patients with hemorrhagic shock before Tx becomes available. Those who received the RBCs within 60 min of injury had a significantly higher survival rate than those who received it later (> or =60 min). The Red Cross Blood Center provided 411 units of RBC for 138 urgent requests for rare blood types. Our analysis suggests that if an AOC were available for the initial six units, 96% of such requests could have been covered to avoid urgent donor allocation, preparation, and Tx. Among 2079 surgical cases who ordered T/S, only 29% actually required Tx, rendering >70% of the T/S unnecessary. Because only 7.4% required nine units or more, more than 92% of T/S and Tx could have been avoided in retrospect if an AOC were available for the initial eight units. The results suggest that an AOC might be useful in various situations to alleviate problems, concerns, and technical burden in the current Tx practices. Because the expected utility is based mainly on physical characteristics, AOC may remain advantageous even when biogenetically derived RBC becomes available.

Effect of Liposome‐Encapsulated Hemoglobin on Antigen‐Presenting Cells in Mice

“…Clinical needs for transfusion often derive from trauma and/or surgery, involving concurrent exposure to pathogens and/or tumor antigens. We have been using type O Rh (+)‐washed and ‐packed RBCs for emergency transfusion for patients with hemorrhagic shock before identical RBCs become available (12). Although a shortened ischemic period has been demonstrated to be advantageous in terms of survival over the risk of minor mismatch transfusion (12), the volume of transfusion derived from a 400‐mL package amounted to 3.05 ± 1.20 units of washed and packed RBCs.…”

“…Circulation half‐life (T 1/2 ) of LEH and HbV depends on species as well as doses; it is approximately 1 day in rodents (4–9) and 2–3 days in primates when 10–20 mL/kg is used (10,11). While LEH is removed from the circulation and disposed of by the reticuloendothelial system (RES) similarly to RBCs, the possible use of LEH for emergency transfusion before identical donor blood becomes available (12) may impose an acute metabolic load of hemoglobin and lipids on RES or antigen‐presenting cells (APCs), such as dendritic cells (DCs) or macrophages, which plays a pivotal role in the triggering of the host's immune defense against third‐party antigens. Thus, this raises a serious concern, as hemorrhagic shock patients are often exposed to pathogens at accidents or surgery causing acute blood loss necessitating emergency transfusion (12).…”

“…While LEH is removed from the circulation and disposed of by the reticuloendothelial system (RES) similarly to RBCs, the possible use of LEH for emergency transfusion before identical donor blood becomes available (12) may impose an acute metabolic load of hemoglobin and lipids on RES or antigen‐presenting cells (APCs), such as dendritic cells (DCs) or macrophages, which plays a pivotal role in the triggering of the host's immune defense against third‐party antigens. Thus, this raises a serious concern, as hemorrhagic shock patients are often exposed to pathogens at accidents or surgery causing acute blood loss necessitating emergency transfusion (12). In our previous study (4), a single injection of LEH at a moderate dose (10 mg/kg) did not largely affect the murine or human immune status nor did it interfere with the host's early response to bacterial enterotoxins (toxic shock syndrome toxin‐1 [TSST‐1]), so far as lymphocyte cellularity and interleukin (IL)‐2 producibility were concerned.…”

Liposome-Encapsulated Hemoglobin Ameliorates Ischemic Stroke in Nonhuman Primates: An Acute Study

“…Although liposomes are much smaller (230 nm), their O 2 -carrying capacity is equivalent to human RBCs under room air respiration (Kaneda et al, 2009). These physical characteristics prompted us to examine the therapeutic potential of LEH, not as an RBC substitute (Yoshiba et al, 2009), in a rodent model of photochemically induced thrombosis of the middle cerebral artery (MCA) (Kawaguchi et al, 2007) and showed that the cortex was significantly better protected than basal ganglia in 24 h. Here, the effects of LEH were quantitatively assessed by steady-state 15 O-gas inhalation…”

“…Although liposomes are much smaller (230 nm), their O 2 -carrying capacity is equivalent to human RBCs under room air respiration (Kaneda et al, 2009). These physical characteristics prompted us to examine the therapeutic potential of LEH, not as an RBC substitute (Yoshiba et al, 2009), in a rodent model of photochemically induced thrombosis of the middle cerebral artery (MCA) (Kawaguchi et al, 2007) and showed that the cortex was significantly better protected than basal ganglia in 24 h. Here, the effects of LEH were quantitatively assessed by steady-state 15 O-gas inhalationThis work was supported in part by a grant-in-aid for scientific research from The Ministry of Education, Culture, Science, and Technology, Tokyo, Japan [Grants 14370365, 16209037, 20249072]; New Energy Development Organization, Tokyo, Japan; Japan Science and Technology Agency, Tokyo, Japan; and CREST, Japan Science and Technology Agency, Saitama, Japan.Article, publication date, and citation information can be found at http://jpet.aspetjournals.org. doi:10.1124/jpet.109.160051.…”