Anaphylactic reaction induced by a polysulfone/polyvinylpyrrolidone membrane in the 10th session of hemodialysis with the same dialyzer : Anaphylaxis induced by polysulfone dialyzer

During hemodialysis, cardiopulmonary decompensation may appear in uremic patients, possibly caused by plugging of pulmonary vessels by leukocytes. In 34 patients we noted leukopenia (20% of initial levels) during hemodialysis that in 15 was associated with impaired pulmonary function. When we infused autologous plasma, incubated with dialyzer cellophane, into rabbits and sheep, sudden leukopenia and hypoxia occurred, with doubling of pulmonary-artery pressures and quintupling of pulmonary-lymph effluent. Histologic examination showed severe pulmonary-vessel-leukostasis and interstitial edema. The syndrome was prevented by preinactivation of complement but was reproduced by infusions of plasma in which complement was activated by zymosan. Thus, acute pulmonary dysfunction from complement-mediated leukostasis may play a major part in the acute cardiopulmonary complications of cellophane-membrane hemodialysis.

Acute leukopenia occurs in all patients during the first hour of hemodialysis with cellophanemembrane equipment. This transient cytopenia specifically involves granulocytes and monocytes, cells which share plasma membrane reactivity towards activated complement components. The present studies document that complement is activated during exposure of plasma to dialyzer cellophane, and that upon reinfusion of this plasma into the venous circulation, granulocyte and monocyte entrapment in the pulmonary vasculature is induced. During early dialysis, conversion of both C3 and factor B can be demonstrated in plasma as it leaves the dialyzer. Moreover, simple incubation of human plasma with dialyzer cellophane causes conversion of C3 and factor B, accompanied by depletion of total hemolytic complement and C3 but sparing of hemolytic C1. Reinfusion of autologous, cellophane-incubated plasma into rabbits produces selective granulocytopenia and monocytopenia identical to that seen in dialyzed patients. Lungs from such animals reveal striking pulmonary vessel engorgement with granulocytes. The activated complement component(s) responsible for leukostasis has an approximate molecular weight of 7,000-20,000 daltons. Since it is generated in C2-deficient plasma and is associated with factor B conversion, it is suggested that activation of complement by dialysis is predominantly through the altermative pathway.

Hydrophilic polysulfone membranes (PVP-PSf) were prepared from polysulfone membranes covalently conjugated with polyvinylpyrrolidone (PVP) on the surface. The immobilized amount of vinylpyrrolidone on PVP-PSf membranes was controlled by the amount of vinylpyrrolidone monomer in the reaction solution and the reaction time. The PVP-PSf membranes were found to be the most hydrophilic membranes among the polysulfone and surface-modified polysulfone membranes prepared in this study. This is explained by the long hydrophilic side chain of polyvinylpyrrolidone on the PVP-PSf membranes which contributes to the hydrophilic wiper on the hydrophobic PSf membranes. It was found that PVP-PSf membranes gave lower protein adsorption from a plasma solution than polysulfone and other surface-modified membranes (p < 0.01). This is attributed to the hydrophilic surface of the PVP-PSf membranes, because the hydrophilic surface is known to reduce the protein adsorption on the membranes. The PVP-PSf membranes showed a much suppressed number of adhering platelets on the surface than polysulfone and other surface-modified membranes (p < 0.01). It is suggested that the hydrophilic surface of the PVP-PSf membranes without ionic groups causes the suppression of platelet adhesion on the PVP-PSf membranes and that the long hydrophilic side chain of polyvinylpyrrolidone on PVP-PSf membranes contributes to the hydrophilic and hemocompatible wipers on the surface of the hydrophobic PSf membranes.