Pulmonary capillary leukostasis: a complement (C') mediated complication of hemodialysis

Uremic patients (pts) may develop unexplained and occasionally fatal cardiorespiratory embarrassment during the first 30' of hemodialysis. Since severe transient neutropenia consistently occurs during this same period, the authors sought a relationship between the two. Indeed, in 10 of 12 pts, PMNs and P(a)O₂ fell simultaneously (95%; 15 to 25 mm) while alveolo arterial O₂ gradients rose 50 to 70%. P(a)O₂ and PMNs normalized after 1 hr. C' activation by dialysis coil cellophane underlay these phenomena. Thus, total C' fell 30 to 40% with hemodialysis or simple 15' incubation of plasma with coil cellophane. Coil activated plasma quintupled PMN adherence to plastic unless preheated (56°C) to destroy C'. Autologous cell exposed plasma reinfused in rabbits causes simultaneous neutropenia and P(a)O₂ drops unless pretreated by 56° or EDTA; EGTA/Mg is ineffective, implicating alternate pathway C' activation in these phenomena. After 20' infusion, lungs show intense capillary leukostasis with PMN margination and plugging, and quintupled tissue lysozyme; no hypoxia occurs in agranulocytic rabbits. In sheep with cannulated pulmonary blood and lymph vessels, infusion of coil plasma causes: severe neutropenia; 95 to 99% pulmonary A V PMN differences; 20 to 30 mm P(a)O₂ drops; 25 to 30 mm rises in pulmonary A pressure; and quadrupled lymph flow and lysozyme content, but not in agranulocytic animals. Zymosan (a known C' activator) added to normal plasma, reproduces all the abnormalities. The authors conclude that alternate pathway C' activation by dialysis coils renders PMN 'sticky' in vitro and occlusive to lung capillaries in vivo. Resulting hypoxia, pulmonary hypertension, and fluid transudation may be fatal in compromised uremics. The pathogenesis of anaphylactoid pulmonary edema and hypoxia following diverse antigen infusions is probably similar.