DNA or RNA with cross‐links. Riboflavin damages DNA upon exposure to UV light. Both methods prevent nucleic acid replication. Thus, contaminating pathogens are inactivated, but platelets are not damaged. Extensive toxicity, mutagenicity, and pharmacologic studies have given satisfactory results. The psoralen product has satisfactory coagulation factor levels and provides posttransfusion increases in coagulation factors similar to ordinary FFP [131]. The riboflavin‐treated FFP also has satisfactory levels of coagulation factors [132]. Because these products are relatively new, there is little clinical experience reported, but the psoralen product is effective in patients with bleeding due to liver disease [134] and for replacement in patients with thrombotic thrombocytopenic purpura [135]. Plasma treated with the psoralen method is now FDA approved for use in the United States.
Table 5.11 Coagulation factor and inhibitor levels in 12 lots of Octaplas.
Source: Adapted from Solheim BG, Hellstern P. Composition, efficacy, and safety of S/D‐treated plasma. Transfusion 2003; 43:1176–1178.
| Measure | Reference range | Octaplas (n = 12)a |
| PT (s) | 12.5–16.1 | 13.3 (12.9–13.8) |
| aPTT (s) | 28–40 | 35 (34–37) |
| Fibrinogen (g/L) | 1.45–3.85 | 2.5 (2.4–2.6) |
| Prothrombin | 65–154 | 83 (79–86) |
| Factor V (U/100 mL) | 54–145 | 78 (75–84) |
| Factor VII (U/100 mL) | 62–165 | 108 (90–117) |
| Factor X (U/100 mL) | 68–148 | 78 (75–80) |
| Factor VIIa (mU/mL) | 25–170 | 166 (134–209) |
| Protein C activity (U/100 mL) | 58–164 | 85 (81–87) |
| Protein S activity (U/100 mL) | 56–168 | 64 (55–71) |
| PI (U/100 mL) | 72–132 | 23 (20–27) |
| Plasminogen (U/100 mL) | 68–144 | 96 (92–101) |
| Citrate (mM) | 17.5 (14.2–20.9) |
aPTT, activated partial thromboplastin time; PT, prothrombin time.
a Data are reported as mean (range).
Platelets
Three methods used for pathogen inactivation of FFP are also being used to treat platelets [118–121, 136–138]. Initial studies in healthy research subjects and studies in patients with thrombocytopenia indicate satisfactory platelet function for both the psoralen and riboflavin methods [138–140]. Successful clinical trials in Europe using psoralen‐treated platelets prepared by the buffy coat method [141] and in the United States using apheresis platelets [142, 143] have been reported, and those platelets are widely used in Europe [144]. Riboflavin‐treated platelets also appear to be clinically effective [145]. Follow‐up of large numbers of patients do not indicate any unexpected adverse consequences from use of the psoralen‐treated platelets [146].
Red cells
Two different approaches are under development for inactivation of transfusion‐transmissible pathogens in RBC components. These involve riboflavin [147] and an alkylating agent [148]. The methods involve selective damage to nucleic acid strands, thus inactivating contaminating pathogens while sparing red cells [122]. The methods are effective against most common bacteria, viruses, and protozoa that would be of concern in blood transfusion [122].
Red cells treated with S303 for pathogen inactivation had in vitro properties similar to paired untreated controls for hemolysis, glucose consumption and potassium release, lower lactate levels and pH, and higher ATP, with significant loss of 2,3‐DPG. Thus, in vitro studies of S303 red cells are essentially not significantly different from untreated red cells [148–151].
A clinical trial in cardiovascular surgery was successful, except that two patients developed clinically nonsignificant antibodies to the treated red cells [152]. That method has been revised, and the clinical trial of the revised method in chronically transfused patients with thalassemia reported no difference in efficacy and safety between the control and study groups [153, 154]. The riboflavin method also results in satisfactory red cells [155], and a clinical trial of that WB product prevented transfusion‐transmitted malaria [156].
Inactivation of viruses and bacteria in cellular components, a strategy almost unthinkable a decade ago, is also showing exciting promise with a platelet and two plasma products now FDA approved in the United States. If a WB/red cell technology becomes available, there will certainly be a major impact on the blood supply system and the nature of blood centers producing these components. See Chapter 16 for more details on pathogen inactivation technology.
5.10 Universal red cells
Two approaches have been attempted to convert A or B red cells to type O. If such a process became practical and widely adopted, it could have a huge impact on blood banking by eliminating most inventory management issues and making more blood available by eliminating outdating of type A and B units. Development of these technologies has been difficult, and neither is near clinical use.
Enzymatic cleavage of ABO and Rh antigen
Enzymes can cleave the sugars that confer A and B specificities [157, 158]. The enzymes for this cleavage have been cloned and are available on a scale sufficient to allow for the production of clinical doses of red cells from which the A and B antigens have been removed. Most of the experience involves successful conversion of group B to group O [157]. Although A‐to‐O conversion is possible, some A determinants remained on the carbohydrate, and this work was halted. Clinical trials of enzymatically converted B type RBCs on healthy volunteers reported no signs of hemolysis [157].
Masking ABO antigens
A different approach to altering the RBC membrane to convert group A or B red cells into group O red cells is to mask the antigens to produce “stealth” red cells. Polyethylene glycol has been used to covalently bond to red cells to mask blood group antigens, such as ABO, Rh, Kell, and Kidd [159]. Small studies in animals suggest that there is little in vitro damage to the red cells and that they have a normal survival, although such studies have not yet been carried out in humans. It is not clear whether development of this process will continue.
5.11 Blood substitutes
The functions of blood can be grouped generally as maintenance of intravascular volume, delivery of oxygen to tissues,