POSTINFECTIOUS PURPURA FULMINANS CAUSED BY AN AUTOANTIBODY DIRECTED AGAINST PROTEIN

Objective. To determine the mechanism responsible for idiopathic purpu ra fulminans, we investigated the procoagulant and anticoagulant pathw ays in five consecutive patients, four after varicella, and the fifth after a nonspecific infection. Methods. Procoagulant and anticoagulant factors, including protein C, protein S, and antithrombin III, were m easured by quantitative or functional assays. Anti-protein S autoantib odies were identified by dot blotting and Western blotting, and quanti fied serially by enzyme-linked immunosorbent assay, Clinical and labor atory data were collated retrospectively. Results, In each case the di sease began 7 to 10 days after the onset of the precipitating infectio n, with rapidly progressive purpura leading to extensive areas of skin necrosis. The illness was complicated by impaired perfusion of limbs or digits (two patients), peripheral gangrene resulting in an above-kn ee amputation (one patient), and major organ dysfunction caused by thr omboembolic phenomena involving the lungs (two patients), the heart (o ne patient), or the kidneys (one patient), Protein S levels were virtu ally undetectable at the time of admission and failed to respond to in fusions of fresh frozen plasma, despite correction of other procoagula nt and anticoagulant factors. All five children had anti-protein S IgM and IgG autoantibodies, which persisted for less than 3 months after admission, Decline in the anti-protein S IgG antibody concentration wa s associated with normalization of the plasma protein S levels. Conclu sions, Autoimmune protein S deficiency may be a common mechanism causi ng postinfectious idiopathic purpura fulminans, Recognition of the pat hophysiologic mechanism may provide a rational basis for treatment. Im mediate heparinization, infusions of fresh frozen plasma, and, in case s complicated by major vessel thrombosis, the use of tissue-type plasm inogen activator may limit thromboembolic complications.