Are inactivation procedures for blood products good or bad?

Editor—In their report on recent developments in transfusion medicine, Regan and Taylor mention that, in future, infectious diseases transmitted by cellular blood products might be prevented by inactivation procedures.¹ All pathogen inactivation procedures for cellular blood products involve one step, and failure cannot be compensated by a second step.

Owing to technical constraints, validation of procedures is limited to five to seven logs. Without screening (or a virus carrier escaping the screening process), however, a platelet concentrate from a hepatitis B virus carrier might contain up to 5×10¹⁰ virus particles per ml. Parvovirus B19 load might exceed 10¹³ viruses per platelet concentrate. Moreover, validation of inactivation procedures relies mainly on the comparability of the model viruses to the relevant human viruses (for example, hepatitis B, hepatitis C), which is a matter of constant debate. Thus, implementation of inactivation does not allow nucleic acid amplification tests to be given up but might even pave the way for additional such tests to limit the pathogen load.

All inactivation procedures affect not only the pathogen but also to some degree the active ingredient. It could be argued that subtle differences not detected by clinical trials do not matter, but recent experience with solvent/detergent treated plasma has shown the contrary.²,³

If pathogen inactivation works by modifying pathogens' nucleic acids, residual amounts of the inactivating substance in the product might also affect the nucleic acids of the transfusion recipient, resulting in possible mutagenicity and carcinogenicity—there is said to be no threshold for mutagenicity and carcinogenicity. Manufacturers try to rule out these side effects by extensive pharmacological and toxicological studies precisely defined by the regulatory authorities. But can these studies also exclude very low incremental risks of carcinogenicity in humans?

The risk of dying from infectious diseases through cellular blood products is vanishingly small: about two in 1 million transfusions (one in 5 million for HIV and one in 600 000 for bacteria,⁴ while no cases of hepatitis C virus have occurred in Germany since the polymerase chain reaction was introduced). I think that pathogen inactivation is only justified if it has a net benefit—if death by malignancies and other side effects through the inactivated product does not exceed the number of patients saved from death by infection. Pathogen inactivation might seem attractive for the public and politics. Establishing its benefit will be a challenge for manufacturers and regulatory authorities.