Variant CJD (vCJD) is an incurable, infectious human disease, likely arising from the consumption of BSE-contaminated meat products. Whilst the epidemic appears to be waning, there is much concern that vCJD infection may be perpetuated in humans by the transfusion of contaminated blood products. Since 2004, several cases of transfusion-associated vCJD transmission have been reported and linked to blood collected from pre-clinically affected donors. Using an animal model in which the disease manifested resembles that of humans affected with vCJD, we examined which blood components used in human medicine are likely to pose the greatest risk of transmitting vCJD via transfusion. We collected two full units of blood from BSE-infected donor animals during the pre-clinical phase of infection. Using methods employed by transfusion services we prepared red cell concentrates, plasma and platelets units (including leucoreduced equivalents). Following transfusion, we showed that all components contain sufficient levels of infectivity to cause disease following only a single transfusion and also that leucoreduction did not prevent disease transmission. These data suggest that all blood components are vectors for prion disease transmission, and highlight the importance of multiple control measures to minimise the risk of human to human transmission of vCJD by blood transfusion.

The majority of blood PrP(c) is found in the platelet and plasma compartments.

Reduced circulating levels of a -antitrypsin (ajAT) are associated with certain ajAT genotypes and increased susceptibility to emphysema. Unfortunately, the amounts of ajAT that would be required for replacement therapy are beyond the capacity of plasma fractionation and mammalian cell culture systems. Thus, we have examined the potential of transgenic animals as an alternative means of producing human ajAT. A hybrid gene constructed by using sequences from the ovine milk protein gene P-lactoglobulin fused to an ajAT "minigene" was used to generate transgenic mice. Of 13 independent transgenic mice and mouse lines, 5 expressed the hybrid gene in the mammary gland, 5 in the salivary glands, and 2 in both these tissues. Human ajAT was secreted into the milk of each of the 7 mice and mouse lines that expressed the hybrid gene in the mammary gland. Four of these mammary-expressing transgenic mice and mouse lines produced concentrations of at least 0.5 mg of ajAT per ml in their milk; one line (AATB 35) produced 7 mg of this protein per ml.ajAT from transgenic mouse milk was similar in size to human plasma-derived ajAT and showed a similar capacity to inhibit trypsin. Expression at equivalent levels in transgenic sheep or cattle would yield sufficient ajAT for therapeutic purposes.Genetic deficiencies of a1-antitrypsin (a1AT) in humans are common and result in an increased susceptibility to emphysema (1). Human a1AT is a 394-amino acid glycoprotein that acts as a suicide inhibitor of a wide range of serine proteases.In humans, the ajAT gene is expressed in a variety of tissues, including macrophages, kidney, small intestine, pancreas, and liver; the latter is the primary site of expression (1, 2). In normal humans, more than 2 g of a1AT is synthesized daily, resulting in a serum concentration of -2 mg/ml. (5) proposed that valuable proteins could be harvested from transgenic animals. We have argued that the mammary gland is the organ of choice for the expression of recombinant proteins (6,7) because large amounts of protein can be synthesized by the mammary gland, secreted into milk, and collected easily without detriment to the animal. We have decided to use sheep for this purpose and have recently demonstrated the production of human factor IX and a1AT in the milk of transgenic sheep (8, 9). In these sheep, and also in transgenic mice carrying the same hybrid genes, the levels of expression of the transgenes were low. The comparisons of the performance of these hybrid genes (FIXA and AATA) in transgenic sheep and mice are the subject of separate studies (M.M., A

The results suggest that SSP+ could be used for platelet storage for up to 9 days. However, the preparation of platelets in the additive requires some optimization. In vivo studies are required to confirm these in vitro results.

ESC and HSR test results are significantly affected by the test diluent. Platelets should be diluted in plasma (preferably autologous) for the in vitro testing of ESC and HSR, regardless of the media in which they are stored.