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In intensive care medicine, convection-based apheresis is of growing interest. Applying extracorporeal systems in the critically ill patient can cause severe complications like nosocomial infections and bleeding, which can be worsened or even initialized by the anticoagulation protocol used. Furthermore, the filter modules (hemo- and plasmafilters) often tend to a fast blockage. A decrease in sieving performance due to membrane fouling may be tolerable for some time, but the complete blockage of high percentages of hollow fibers, which is named "clotting," often requires the immediate exchange of the filter. Extracorporeal detoxification and high clearance renal replacement regimes both require high blood flow and filtration rates. As a consequence, filter clotting and anticoagulation-associated bleeding are the most sensitive aspects in these applications. We were interested in the paradox phenomenon of the parallel occurrence of intra vitam bleeding and filter clotting in critically ill patients. Through stepwise investigations based on in vitro and animal experiments, we identified a stasis of blood flow followed by blood cell sedimentation and aggregation ("clogging") as the main factor of hollow fiber blockage in hemo- and plasma filters. As a result, various aspects which increase the risk of stasis inside the hollow fibers were investigated, for example, patient's hemorheology, configuration of an extracorporeal treatment system including interaction of catheter features with the filtration procedure, and basic therapeutic approaches such as colloidal volume substitutes and tolerated acidosis. Finally, an etiological triad for the blockage of hollow fibers due to filter clogging and consecutive filter failure was formed., (© 2013, Copyright the Authors. Artificial Organs © 2013, International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.)