Postinfectious purpura fulminans caused by an autoantibody directed against protein S☆,☆☆,★,★★
Section snippets
Patient 1
A previously healthy boy aged 6.4 years was transferred to us because of rapidly developing purpura. Five days before admission, fever, malaise, and a vesicular rash over his groin had begun. During the next 3 days he remained intermittently febrile, but his condition seemed to be improving symptomatically until the onset of a generalized macular eruption, which progressed to purpura. He had had chickenpox 1 year previously. There was no family history of thromboembolism. On examination he was
METHODS
Plasma coagulation tests (PT, activated partial thromboplastin time, fibrinogen, and D-dimer concentrations) were determined by standard methods. Total and free protein S concentrations were measured by ELISA as previously described.20 Protein S activity was measured by a clotting assay (Staclot Protein S, Diagnostica-Stago, Asnieres, France). Plasma concentration of complement C4b binding protein was measured by Laurell Rocket electrophoresis by means of a C4bBP-specific antiserum (Nordic
RESULTS
All five patients had virtually undetectable levels of free protein S at the time of admission, together with markedly reduced levels of total protein S (Fig. 1). In all cases, despite daily infusions of up to 60 ml FFP per kilogram of body weight, free protein S levels remained markedly reduced for 1 to 2 weeks after admission and thereafter rose slowly to within the normal range. Total protein S levels recovered more quickly than free protein S but remained below normal for several days after
DISCUSSION
Reviews by Hjort et al.3 and Francis4 delineated the characteristic features of idiopathic PF. Most cases occur in children. More than 90% are preceded by infection, commonly varicella or a streptococcal infection.4 The disease begins suddenly with the development of progressively enlarging, well-demarcated purplish black areas of haemorrhagic cutaneous necrosis with deranged coagulation factors. The overall mortality rate in cases reported before 1964 was more than 50%.3 In more recent reports
CONCLUSION
Postinfectious purpura fulminans after varicella, mediated by autoantibodies against protein S, appears to be a distinct clinical and pathophysiologic entity. Recognition of this disorder may facilitate appropriate treatment. Although it is possible that postinfectious purpura fulminans may be mediated by other mechanisms, recognition of autoimmune protein S deficiency in five consecutive patients with PF indicates that this mechanism may be common.
We are grateful for expert help and advice
References (42)
Haemophilus aegyptius bacteremia in Brazilian purpuric fever
Lancet
(1987)- et al.
An abnormal plasma distribution of protein S occurs in functional protein S deficiency
Blood
(1986) Quantitative estimation of proteins by electrophoresis in agarose gel containing antibodies
Anal Biochem
(1966)- et al.
An automated Western blot analysis using the Phastsystem
Anal Biochem
(1988) - et al.
The co-factor role of protein S in the accelaration of whole blood clot lysis by activated protein C in vitro
Blood
(1986) - et al.
Protein S and HIV infection. The role of anticardiolipin and anti–protein S antibodies
Thromb Res
(1994) - et al.
Antiphospholipid antibodies directed against a combination of phospholipids with prothrombin, protein C, or protein S: an explanation for their pathogenic mechanism?
Blood
(1993) Ueber Purpura fulminans
Berl Klin Wochenschr
(1887)- et al.
Dermatopathology of skin necrosis associated with purpura fulminans
Semin Thromb Hemost
(1990) - et al.
Purpura fulminans: report of a case successfully treated with heparin and hydrocortisone: review of 50 cases from the literature
Scand J Haematol
(1964)
Acquired purpura fulminans
Semin Thromb Hemost
Purpura necrotica as a complication of ventriculoatrial shunts in hydrocephalus
Arch Dis Child
Purpura fulminans following late-onset group B βhemolytic streptococcal sepsis
Am J Dis Child
The orthopaedic implications of purpura fulminans
J Bone Joint Surg
Symmetrical peripheral gangrene (purpura fulminans) complicating pneumococcal sepsis
Am J Surg
Purpura fulminans associated with H. influenzae type b infection
N C Med J
Meningococcal infections in children: a review of 100 cases
Pediatr Infect Dis J
Pathogenesis of cutaneous lesions in acute meningoccocaemia in humans: light, immunofluorescent, and electron microscopic studies of skin biopsy specimens
J Infect Dis
Neonatal purpura fulminans due to homozygous protein C or protein S deficiencies
Semin Thromb Hemost
Proposed classification and pathologic mechanisms of purpura fulminans and skin necrosis
Semin Thromb Hemost
Purpura fulminans in meningococcaemia: asssociation with acquired deficiencies of protein C and S
N Engl J Med
Cited by (0)
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From the Paediatric Infectious Diseases Unit, Department of Paediatrics, and the Department of Haematology, St. Mary's Hospital Medical School, London, and the Haemostasis Research Unit, University College, London, United Kingdom
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Supported by the Max Friedman Trust (Dr. Eley) and the Wellcome Trust (Dr. Heyderman).
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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.
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