Therapeutic apheresis has undergone a real technological revolution in recent years, with the adoption of procedures targeted at the most selective possible removal of pathological components present in the blood. These technological innovations and the ever more widespread adoption of evidence-based indications in the field of medicine have made it necessary for scientific societies to draw up guidelines on the clinical indications for the use of therapeutic apheresis1. Over the years, the Guidelines of the American Society for Apheresis (ASFA) have represented the main reference source for clinicians to evaluate the appropriateness of therapeutic apheresis. In 2010, only 3 years after the 2007 edition, the Fifth Edition of the Guidelines on the Use of Therapeutic Apheresis in Clinical Practice, drawn up by the Apheresis Application Committee of the ASFA, were published2. This new edition of the ASFA guidelines, like its preceding edition, used the methodological criteria of evidence-based medicine in evaluating the appropriateness of apheresis therapy, adopting the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system, which is used to evaluate scientific literature3. The GRADE system classifies the level of scientific evidence in relation to its scientific and methodological quality and translates it into recommendations of various strengths. This methodological updating of the guidelines enables the clinician to transfer the scientific evidence immediately into daily clinical practice. Applying this method of evaluating scientific literature to the clinical use of therapeutic apheresis has been the key to overcoming the limitation inherent in the preceding definition of ASFA Categories of indications for apheresis, which was based on expert consensus. Using the GRADE system to redefine the criteria for assigning pathologies to treat into ASFA Categories has been particularly useful for overcoming the previously present dichotomy separating Categories I and II, seen as the only “real” indications for apheresis therapy, from Category III. The redefinition draws attention back to the pathologies in Category III which, in particular clinical situations, can have a strong grade of recommendation for therapy, even in the presence of lower levels of scientific evidence, such as that provided by series of clinical cases. Furthermore, the consultation of the indications for treatment for individual diseases has been improved by the use of summary fact sheets in which the pathology, pharmacological treatment, and rationale and technical characteristics of the apheresis treatment are summarised and in which the ASFA Category with relative levels of evidence and recommendations are reported. An examination of the ASFA 2010 guidelines shows that the traditional technique of therapeutic plasma exchange (TPE) is still the most widely used apheresis procedure because of its simplicity and cheapness, particularly in clinical situations in which therapeutic apheresis must be carried out urgently. It should, however, be noted that the Apheresis Application Committee of the ASFA deliberately avoided, both in the introductory part and in the fact sheets dedicated to the individual diseases, dealing with the organisational aspects of managing critical situations by giving rules on the timing with which to carry out therapeutic apheresis (emergencies within a few hours, urgent cases within 24 hours, or planned treatment) since the presentation and progression of diseases requiring treatment differ in each patient. The Apheresis Application Committee of the ASFA simply states that the patient’s condition and clinical context must be considered individually when deciding the time to use apheresis treatment and that this decision must be taken on the basis of medical judgement after consultation between the clinician requesting the treatment and a doctor expert in apheresis. Since every patient is unique and there is a broad range of disease presentations and evolutions, it is not possible to categorise diseases and disorders to be treated with apheresis using the criterion of the timing of the treatment, even though there are pathologies in which therapeutic apheresis is among the acute treatments and should be carried out as soon as possible, such as thrombotic thrombocytopenic purpura, acute chest syndrome in sickle cell disease, thrombocytosis, hyperleucocytosis, hyperviscosity syndrome and malaria2. Returning to the statements of the ASFA, we can, therefore, define “urgent plasma exchange” as an apheresis treatment that is initiated as early as possible, and not beyond 24–36 hours after the clinical diagnosis, when the patient’s life is threatened and there are no valid therapeutic alternatives. We believe that is useful to examine carefully some technical and organisational aspects presented in the guidelines on how, why and when to conduct an urgent TPE procedure.