Plasma pool size and the safety of plasma derivatives

For several decades, various preparations of coagulation factors VIII and IX have played an invaluable role in the treatment of the hemophilias. As their availability increased, the effectiveness and convenience of freezedried concentrates of these factors made them the treatment of choice for many patients, notwithstanding the associated high risk of hepatitis. At the time of the recognition of the human immunodeficiency virus transmission risk associated with these products, measures for virus inactivation directed at hepatitis viruses were beginning to show promise. The detection and removal of virus-contaminated donor plasma and virus inactivation of the final products have vastly increased product safety in recent years.' The possibility that new agents contaminating these products will emerge and the resistance of certain known viruses to current inactivation methods justify not only intensive surveillance, but also continuing efforts to develop and apply new solutions to the problem of viral contamination of plasma pools. To this end, a variety of approaches have been tried or recommended over the years2 One suggested approach for reducing the risk of pathogen transmission by pooled plasma derivatives is the use of smaller pools to lower the likelihood that a contaminating unit will find its way into an individual pool. In this issue of TRANSFUSION, Lynch et aL3 report on reductions in the number of donor units entered into plasma pools and the effect of those reductions on the risk of exposure to contaminating microbes in the recipients of such units. Their study is exemplary of the kind of analysis needed in considering this and other measures for increasing the safety of blood and blood products. These authors show that, except in the case of extremely rare pathogens, a reduction in pool size is not a very promising approach to increasing the safety of pooled plasma products in persons who require frequent treatment over many years, such as persons with moderate or severe clotting factor deficiencies. Very similar conclusions were reached by an earlier group commenting on the small-pool strategy, but with less thorough mathematical m~del ing .~ Lynch et al. demonstrate that large pools are highly likely to be contaminated and that large reductions in pool size are necessary to lower this likelihood, unless the prevalence of the agent in the donor population is extremely low. Furthermore, when an individual's lifetime treatment requires as many as 100 lots of a pooled plasma derivative, the likelihood of exposure to a contaminating agent is 63 percent when only one of the pools is contami-