VIRAL INACTIVATION IN PLATELET CONCENTRATES

Although the current risk of posttransfusion infection is very low in North America and Western Europe, there continues to be considerable interest in measures to inactivate residual viruses in blood components. The human immunodeficiency virus is of greatest concern, but hepatitis C virus is also considered to be a significant problem. HTLV-I and -II and HBV may also be transmitted by transfusion, although infrequently. It is likely that effective inactivation methods will have to reduce viral titers by about 6 orders of magnitude, including both viruses found free in plasma and those in intracellular compartments. Although it would be most desirable to have a single procedure to inactivate viruses in all blood components, it appears that different methods may be required for plasma, red cells and platelets. To date, the most promising approach for platelets appears to be photochemical inactivation. In general, photoactive compounds fall into two major groups: photodynamic dyes which are activated by visible Light and act by oxygen dependent generation of reactive molecular species; and ultraviolet-activated intercalating compounds which form covalent adducts with nucleic acids. We have found that photodynamic inactivators are unable to inactivate viruses in platelet concentrates without damaging the platelets. On the other hand, we have shown that aminomethyl trimethyl psoralen (AMT), when activated by long-wavelength ultraviolet Light (UVA) can inactivate more than 5 logs of model viruses and HIV while platelet in vitro properties are maintained. Further, unlike photodynamic inactivators, AMT is able to inactivate cell-associated and intracellular viruses and also prevents the replication of integrated HIV genome sequences, as demonstrated by PCR. Platelets which have been exposed to antiviral treatment with AMT and UVA also retain their hemostatic effectiveness in an animal model system. One problem with AMT is that it is mutagenic and thus may be inappropriate for infusion into patients. Thus, implementation of a psoralen/UVA inactivation protocol may require the removal of residual drug from the platelet concentrate. An alternate strategy might be to seek psoralens which are non-mutagenic. Finally, in the past year or so, much progress has been made in the use of methylene blue for viral inactivation of plasma. Methylene blue is capable of inactivating free virus in conditions which retain the integrity of platelets. However, it appears to be unable to achieve inactivation of intracellular viruses. Consequently, it is unclear when an inactivation method for platelet concentrates could be available for routine use.