Clostridial gas gangrene. II. Phospholipase C-induced activation of platelet gpIIbIIIa mediates vascular occlusion and myonecrosis in Clostridium perfringens gas gangrene

Clostridium perfringens gas gangrene is a fulminant infection, and radical amputation re mains the single best treatment. It has been hypothesized tha t rapid tissue destruction is related to tissue hypoxia secondary to toxin- induced vascular obstruction, and previous studies demonstrated that phosph olipase C (PLC) caused a rapid and irreversible decrease in skeletal muscle blood flow that paralleled the formation of intravascular aggregates of ac tivated plate lets, fibrin, and leukocytes, In this study, flow cytometry d emonstrated that PLC stimulated platelet/neutrophil aggregation in a gpIIbI IIa-dependent fashion. Pretreatment of animals with heparin or depletion of leukocytes reduced blood-flow deficits, and aggregate formation caused by PLC. It is concluded that fulminant tissue destruction in gas gangrene resu lts from profound attenuation of blood dow caused by PLC-induced, gpIIbIIIa -mediated formation of heterotypic platelet/polymorphonuclear leukocyte agg regates. Therapeutic strategies that target gpIIbIIIa may prevent vascular occlusion, maintain tissue viability, and provide an alternative to radical amputation for patients with this infection.