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Therapeutic cryogel removal in autoimmune disease: what is cryogel. 1982.

Guest Editor's Introduction: This paper was presented as a keynote address of the 2nd congress of the Japanese Society for Therapeutic Plasmapheresis on June 5, 1982. It was printed in Therapeutic Plasmapheresis II (ed) T. Oda, and published by F.K. Schattauer Verlag, Stuggart, Germany in 1982 on pages 15–25. In this paper, attempts were made to clarify the formation of the cryogel, composition of cryogel, and cryogel and its temperature dependence by cryofiltration procedures. Clinical effects of cryogel removal or cryofiltration procedures were described from macromolecular changes, pre and post procedures, and the clinical effects of rheumatoid arthritis patients were assessed from these macromolecular kinetics. Basically, cryogel is a fibrinogen-heparin-fibronection complex and contains various types of pathological macromolecules. 
 
 
 
Abstract: Cryofiltration is the on-line technique of plasma treatment consisting of plasma cooling and its membrane filtration. In cryofiltration, cryogel is formed and removed by the cryofilter. The formation of cryogel on-line at temperatures near 4°C and the removal of cryogel by the membrane filter has been shown to produce positive clinical results in the treatment of rheumatoid arthritis and other autoimmune diseases. Cryogel as generated in cryofiltration is distinct from cryoprecipitate (cryoprotein, cryoglobulin) as isolated by classical laboratory tests or those substances removed by off-line techniques as cryopheresis and cryoglobulinpheresis. Cryogel is formed under conditions of relatively fast cooling (10–20 minutes) and is removed during membrane filtration of the plasma. Cryogel concentrates the pathological molecules, and therefore, is selective for their removal. Clinical and in vitro studies of cryofiltration indicate the primary importance that temperature has on the bulk properties of the solution and the filtration process. While clinical studies to date have been carried out at 4°C, cryogel can form at temperatures below 37°C.  In general we can remove more cryogel from pathological plasma than from normal plasma.  Mechanisms involved in the formation of cryogel are complex and involve multiple plasma solutes. Cold-induced precipitation of macromolecules from plasma is most likely due to the interaction of heparin, fibronectin (cold insoluble globulin), and fibrin/fibrinogen under cooling conditions. Plasma subjected to the cooling procedures contains sufficient amounts of heparin to produce heparin-fibrinogen complex. This complex acts as a nucleus for cryogel formation and the binding of macromolecular weight plasma solutes which are then trapped on the cryofilter.