abstract: The aim of the study was the comparison of the influence of fresh frozen plasma (FFP) (Freiburg, Germany) and Biseko, Biotest Pharma GmbH (Dreieich, Germany), as a plasma substitute (a standardized, virus inactivated human serum protein solution) on the coagulation factors, inhibitors, proteins, and complement factors in the plasma of autoimmune disease patients following membrane plasma separation. Patients (n = 24) with autoimmune disease were randomized to receive either FFP or Biseko for membrane plasma separation therapy. During each plasma exchange, 100% of the plasma volume was replaced by the respective substitute. Plasma exchange volume was performed once daily for 3 days. Target test parameters of the coagulation system were fibrinogen, fibrinopeptide A, factor VIII (FVIIIC), von Willebrand factor antigen (vWFAg), partial thromboplastin time (PTT), thromboplastin time (Quick value), and antithrombin (AT III). The immunoglobulins were IgG, IgA, and IgM and C-reactive protein (CRP). The thrombocytes were platelet factor 4 (PF4), and complement factors were C3 and C4. Biseko was well tolerated with 1 mild adverse drug reaction (ADR) (n = 1) while FFP gave rise to ADR on 7 occasions (n = 4). Statistically significant differences in the 2 groups were observed for fibrinogen, PTT, Quick value, and AT III. From the clinical point of view, all fluctuations and differences in parameter levels remained clinically silent. The differences had no clinical consequences. Reflecting on a potential decrease in the risk of infections in comparison to FFP therapy and the lower rate of adverse drug reactions, it is possible to postulate an advantage of Biseko for plasma exchange therapy.