CPB is not benign and there are a number of associated problems. As a consequence, CPB is only used during the several hours a cardiac surgery may take. CPB is known to activate the coagulation cascade and stimulate inflammatory mediators, leading to hemolysis and coagulopathies. This problem worsens as complement proteins build on the membrane oxygenators. For this reason, most oxygenators come with a manufacturer's recommendation that they are only used for a maximum of six hours, although they are sometimes used for up to ten hours, with care being taken to ensure they do not clot off and stop working. For longer periods than this, an ECMO (extracorporeal membrane oxygenation) is used, which can be in operation for up to 31 days – such as in a Taiwanese case, for 16 days, after which the patient received a heart transplant.