CaridianBCT Biotechnologies Research Articles

Pathogen reduction of fresh plasma using riboflavin and ultraviolet light: effects on plasma coagulation proteins

Treatment with riboflavin and ultraviolet (UV) light reduces the pathogens present in blood components. This study assessed changes to the coagulation proteins that had occurred during this treatment of fresh plasma units before freezing. Twenty fresh plasma units (230 +/- 30 mL) were treated by the Mirasol process (CaridianBCT Biotechnologies) and frozen within 8 hours of donation. Plasma units were combined with 35 mL of a 500 micromol/L riboflavin solution in an illumination bag to achieve a final concentration of approximately 60 micromol/L riboflavin. The bag was placed in the Mirasol illuminator and exposed to UV light (6.24 J/mL). Samples were frozen before and after treatment. Recoveries observed were 67.7 +/- 3.9% Factor (F)XI, 68.5 +/- 3.3% FVIII:C, 78.8 +/- 4.5% fibrinogen, 78.9 +/- 4.1% FV, 79.0 +/- 4.2% FVII, 79.0 +/- 8.6% F IX, 79.7 +/- 2.6% FX, and 85.0 +/- 3.7% FII. Von Willebrand factor (VWF) antigen, VWF:ristocetin cofactor, and ADAMTS13 recoveries were 87.0 +/- 7.1, 85.5 +/- 6.6, and 73.3 +/- 15.2%, respectively, while that of protein C was 83.6 +/- 2.6%. A loss of high-molecular-weight VWF multimers was observed in most units. Recoveries for protein S, antithrombin, and plasmin inhibitor were greater than 90%. The mean FVIII:C concentration, after treatment, was 0.76 +/- 0.17 IU/mL. As with other pathogen reduction technologies, the Mirasol process resulted in some loss of coagulation factor activity. For most Mirasol-treated units and for most of the tested factors this is unlikely to have clinical impact, but trials are required to demonstrate this.

Irradiation eradication and pathogen reduction. Ceasing cesium irradiation of blood products

The irradiation of cellular blood components to prevent transfusion-associated (TA)-GVHD is an established practice in the developed world. Susceptible patients include those who are immunosuppressed, fetuses, very premature neonates and patients who have an increased likelihood of possessing one HLA haplotype for which the blood component donor is homozygous. Problems and challenges associated with blood component irradiation include transfusion delay, cost, failure to irradiate when indicated, increased potassium accumulation in and decreased shelf life of RBC units, reduced RBC recovery and, in the United States, substantial and onerous security requirements for cesium-137 source irradiators and their operators. Microbial contamination of blood components can pose life-threatening risks for transfusion recipients. Donor history screening and infectious disease testing are a reactive response and expensive, as well as an imperfect and incomplete means for preventing these infectious risks. In response to these threats, pathogen reduction technologies have been developed. Two such innovations (INTERCEPT, Cerus Corporation, Concord, CA, USA; and Mirasol, CaridianBCT Biotechnologies, Lakewood, CO, USA) are approved for clinical use in many countries, though not in the United States. These processes have been shown to effectively prevent proliferation of nucleic acid-containing microbes, thereby providing broad protection against transfusion-transmitted infection. These technologies have also been shown to prevent the replication of WBC. In this report, we review the substantial in vitro, clinical trial and clinical practice observational evidence that non-irradiated INTERCEPT- and Mirasol-treated cellular blood components do not cause TA-GVHD. Implementation of these processes precludes the necessity for irradiating cellular blood components to prevent TA-GVHD.