Postinfectious purpura fulminans caused by an autoantibody directed against protein S Michael Levin, FRCP, PhD, Brian S. Eley, FCP(SA), BSc(Hons), Jacques Louis, MD, Hannah Cohen, MRC Path, MD, Usa Young, MSc, and Robert S. Heyderman, MRCP, PhD From the Paediatric Infectious DiseasesUnit, Department of Paediatrics, and the Depart- ment of Haematology, St. Mary's Hospital Medical School, London, and the Haemostasis Research Unit, University College, London, United Kingdom Objecfive. To determine the mechanism responsible for idiopathic purpura fulmi- nans, we investigated the procoagulant and anticoagulant pathways in five con- secutive 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 measured by quantitative or functional assays. Anti-protein S autoantibodies were identified by dot blotting and Western blotting, and quantified serially by enzyme-linked immunosorbent assay. Clinical and laboratory data were collated retrospectively. Results. In each case the disease began 7 to 10 days after the onset of the pre- cipitating infection, 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-knee amputation (one patient), and major organ dysfunction caused by thromboembolic phenomena involving the lungs (two patients), the heart (one patient), or the kidneys (one pa- tient). Protein S levels were virtually undetectable at the time of admission and failed to respond to infusions of fresh frozen plasma, despite correction of other procoagulant 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 was associated with normalization of the plasma protein S levels. Conclusions. Autoimmune protein S deficiency may be a common mechanism causing postinfectious idiopathic purpura fulminans. Recognition of the patho- physiologic mechanism may provide a rational basis for treatment. Immediate heparinization, infusions of fresh frozen plasma, and, in cases complicated by major vessel thrombosis, the use of tissue-type plasminogen activator may limit thromboembolic complications. (J PEDIATR 1995;127:355-63) Supported by the Ma:< Friedman Trust (Dr. Eley) and the Wellcome Trust (Dr. Heyderman). Submitted for publication March 15, 1995; accepted June 1, 1995. Reprint requests: Michael Levin, FRCP, PhD, Paediatric Infectious Disease Unit, Queen Elizabeth the Queen Mother Wing, St. Mary's Hospital Medical School, South Wharf Road, London W2 1NY, United Kingdom. Copyright © 1995 by Mosby-Year Book, Inc. 0022-3476/95/$5.00 + 0 9/20/66744 Purpurafulminans is a descriptive term depicting a hetero- geneous group of disorders characterized by rapidly pro- gressive purpuric lesions, which may develop into extensive areas of skin necrosis and peripheral gangrene, a,2 The disorder is associated with laboratory evidence of con- sumptive coagulopathy. The histopathologic features are widespread thrombosis of the dermal capillaries and venules with hemorrhagic infaretion of the surrounding tissues. 2, 3 The condition is often fatal, and survivors may have consid- 355