Plasmapheresis in Thrombotic Microangiopathy‐Associated Syndromes: Review of Outcome Data Derived from Clinical Trials and Open Studies

Abstract

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%.

Tandem Plasmapheresis and Hemodialysis: Efficacy and Safety

“…PE has reduced TMA mortality in patients from 94.5% to 13%. 9 Many cases of TMA do not develop renal failure that required renal replacement therapy. Three of our patients with TMA needed dialysis, one of whom was dependent on HD at the end of treatment.…”

“…1,2 There are several diseases, such as Goodpasture's syndrome, 1,3,4 rapidly progressive glomerulonephritis (RPGN), 1,2,5-8 thrombotic microangiopathy (TMA) 9 (including hemolytic uremic syndrome 10 and thrombotic thrombocytopenic purpura), and acute humoral rejection (AHR), [11][12][13] for which PE is indicated.…”

Dose kidney transplant nephrectomy stop disease progression in plasma exchange resistant post transplant hemolytic uremic syndrome? A case report

“…While, prior to the use of plasma exchange, the outcome of thrombotic microangiopathy (TMA)-associated syndromes was poor in the last decades, standard plasma exchange has significantly reduced the mortality rate of TTP/ HUS from 94.5% to 13%. Therefore, It is recommended that even if there is some uncertainty about the diagnosis of TTP-HUS, plasma exchange should be initiatedand if an alternative diagnosis is subsequently discovered it should then be stopped (7,8).…”

The role of hematologists in a changing United States health care system

“…18 Treatment involves substantial plasma replacement. In some instances, 25% to 50% of a health system's yearly plasma volume may be used for a few patients with TTP (N.T.C.…”