Current reimbursement policy of health insurance for therapeutic plasmapheresis requires proof of efficacy using the concept of evidence‐based medicine. The aim of this paper is to review the outcome of plasmapheresis used to treat thrombotic microangiopathy (TMA)‐associated syndromes in the last decade to provide scientific evidence to back up reimbursement applications. The strength of evidence of each reviewed study was assessed using the five levels of evidence criteria as defined by the American Society of Hematology in 1996 for assessment of the treatment of immune thrombocytopenia. The level Experimental indication was added for situations where only case reports or small series supported by pathophysiological reasoning are available. The definitions of evidence used in this paper are as follows: Level I, randomized clinical trial with low rates of error (p < 0.01); Level II, randomized clinical trial with high rates of error (p < 0.05); Level III, nonrandomized studies with concurrent control group; Level IV, nonrandomized studies with historical control group; Level V, case series without a control group or expert opinion; and Experimental, case reports and pathophysiological reasoning. The results of this analysis based on the published data is summarized as follows: The indication of plasmapheresis is assigned to Level IV evidence for thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS); cancer/chemotherapy‐associated TTP/HUS is assigned to Level V evidence; and TTP/HUS refractory to standard plasma exchange and post‐bone marrow transplantation TTP/HUS are assigned to Experimental indication. For both subsets, protein A immunoadsorption is reportedly successful. The other TMA‐associated syndromes, hemolysis elevated liver enzymes low platelets and HUS in early childhood, are no indication of plasmapheresis. Two randomized clinical trials were performed in order to demonstrate the superiority of plasma exchange/fresh frozen plasma (PEX/FFP) over plasma transfusion in the management of TTP/HUS. The results prove the greater clinical success of the latter type of plasma administration. Standard PEX/FFP has reduced the mortality of TTP/HUS from 94.5% to 13%.

Background: The rapidly evolving field of transplantation research with a focus on ischemic and reperfusion injuries has gained importance since the methodology of organ preservation significantly limits graft survival. Numerous models of isolated perfused kidneys have been established in the past years but limitations such as organ size, perfusate and ethical standards have restricted a widespread research in this area. Methods: A model of hemoperfused isolated porcine slaughterhouse kidneys was established which encompasses the advantages of autologous blood as optimal perfusate and a reduction of animal experiments. Results: The size and geometry of the porcine kidney is more comparable to human conditions and various renal functions, blood parameters and morphology can easily be accessed in the present model. Stable organ function can be maintained over 2 h with an amount of 500–1,000 ml of autologous blood which is metabolically controlled via a dialysis system. Conclusion: In summary, the present model describes a new and economic approach for targeting renal function in transplantation models by combining autologous blood as optimal perfusate with a well-defined organ geometry and function and slaughterhouse animals as a source.

Glomerulotubular balance (GTB) is defined as the ability of each successive segment of the proximal tubule to reabsorb a constant fraction of glomerular filtrate and solutes delivered to it. For maintenance of GTB the coupling of peritubular blood flow and intratubular fluid flow to the process of glomerular filtration seems to be of functional importance since tubular fluid reabsorption is significantly altered when either or both parameters are experimentally changed. In the case of peritubular blood flow, variations of tubular fluid reabsorption have been ascribed to variations of the mean net colloid osmotic pressure in the peritubular blood and its effects on the paracellular backleak of tubular resorbate. This relationship has, however, been clearly demonstrated only in volume expansion, when GTB is impaired. Under nondiuretic conditions, in which GTB typically occurs, the importance of the peritubular colloid osmotic pressure in control of tubular fluid reabsorption is less clear since variations of peritubular colloid osmotic pressure within a physiologic range exert only a negligible influence on tubular fluid transport. Pharmacologically induced alterations of peritubular hemodynamics or mean net colloid osmotic pressure can affect tubular fluid reabsorption without consistently altering the net interstitial pressure. In the case of intratubular flow rate, variations of tubular fluid reabsorption are comparable to changes seen with GTB. Such an interrelation is found only in tubules perfused by natural tubular fluid. In individual nephrons flow-dependent reabsorption cannot always be observed even when it appears that GTB is preserved in that kidney. Flow dependency of tubular fluid reabsorption might be attributed to some properties or constituents in tubular fluid rather than to some intrinsic characteristics of the tubular epithelium. Because flow dependence and tubular fluid transport are homogeneous along the tubule, fluid reabsorption might be controlled by a mechanism akin to a flow reactor. As yet it is not possible to explain GTB exclusively by peritubular or luminal control alone.

The objective of this paper is to assess the role of plasmapheresis in immune hematology by reviewing published clinical outcome data and narrative review articles. This information will be used to define evidence levels for appraisal of the efficacy and rank of plasmapheresis among other management options. This evidence-based strategy conforms to the concepts of the American Society of Hematology (ASH). as put forward in 1996 in the context of immune thrombocytopenia (ITP) treatment. The term 'experimental' is used to describe indications where the only scientific evidence of the efficacy of plasmapheresis consists of pathophysiological reasoning and empiric clinical findings. We reviewed the available literature on the use of plasmapheresis in autoimmune hemolytic anemia (AIHA), hemolytic disease of the newborn (HDN), autoimmune thrombocytopenic purpura (AITP), heparin-induced thrombocytopenia type II (HIT II), post-transfusion purpura (PTP), refractoriness to platelet transfusion (RPT), coagulation factor inhibitor (CFI) and catastrophic antiphospholipid syndrome (CAS). Plasmapheresis completes the spectrum of management options as it eliminates physically circulating free antibodies involved in the pathogenesis of these immune hematological syndromes. Because of the paucity of data, evidence levels had to be defined based on the findings of uncontrolled case series and the opinions of independent experts. In many cases, randomized clinical trials were not feasible because the syndromes are so rare. When defined as an 'experimental indication', plasmapheresis has a firm scientific basis, but larger scale clinical experience with the method is still lacking. In these cases, the detection and monitoring of symptomatic disease-related circulating free antibodies or immune complexes is a mandatory prerequisite for the use of plasmapheresis. The therapeutic benefit of plasmapheresis is substantiated by the level V of evidence of its efficacy in treatment of HDN, HIV-associated AITP, induction of tolerance in CFI and in CAS. The goal of future studies should be to establish a firmer base of scientific evidence for indications classified as experimental by setting up case series large enough for proper assessment of plasmapheresis alone or combination with other treatment measures. This goal can only be achieved through multiinstitutional cooperation.

No abstract