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Mechanisms of blood coagulation by direct contact of nonthermal atmospheric pressure dielectric barrier discharge (DBD) plasma are investigated. This paper shows that no significant changes occur in the pH or Ca2+ concentration of blood during discharge treatment. Thermal effects and electric field effects are also shown to be negligible. Investigating the hypothesis that the discharge treatment acts directly on blood protein factors involved in coagulation, we demonstrate aggregation of fibrinogen, an important coagulation factor, with no effect on albumin. We conclude that direct DBD treatment triggers selective natural mechanisms of blood coagulation.