A method of reducing pathogens in blood by exposure to a nitric oxide containing gas in an extracorporeal circuitry is provided. The method includes: obtaining blood from a mammal or a blood source, separating the blood into plasma and blood cells, exposing the plasma to nitric oxide containing gas, combining the exposed plasma with the blood cells, reducing nitric oxide content in the recombined blood, and returning the blood to the mammal or blood source.