Affiliations: Section of Critical Care, Department of Pediatrics,
Baylor College of Medicine, Houston, TX, USA | Division of Critical Care, Department of Pediatrics
and Communicable Diseases, University of Michigan Medical School, Ann Arbor,
MI, USA | Critical Care Division, Children's Healthcare of
Atlanta at Egleston, Department of Pediatrics, Emory University School of
Medicine, Atlanta, GA, USA | Departments of Critical Care Medicine and Pediatrics,
University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
Note: [] Correspondence: Trung C. Nguyen, M.D., Section of Critical Care,
Texas Children's Hospital, 6621 Fannin St Wt 6-006, Houston, TX 77030-2399,
USA. Tel.: +1 832 826 6230; Fax: +1 832 825 6229; E-mail:
[email protected]
Abstract: Sepsis is a systemic inflammatory syndrome in response to an
infection. With the current resuscitation practice, up to 16% of children with
severe sepsis and septic shock still progress to develop multiple organ failure
(MOF), a condition that is associated with poor outcome. In this review, we
focus on the thrombotic microangiopathic paradigm for the development of
sepsis-induced MOF. We describe the clinical observations, emerging
experimental and laboratory evidence supporting the concept that sepsis-induced
MOF may be a secondary thrombotic microangiopathy, manifest as
thrombocytopenia-associated MOF. Drawing the pathologic similarities such as a
disintegrin and metalloprotease with thrombospondin motifs-13 deficiency,
impaired ultra-large von Willebrand factor multimers proteolysis, and von
Willebrand factor-rich microthrombi and therapeutic success with plasma
exchange in treating thrombotic thrombocytopenic purpura, a primary thrombotic
microangiopathy, we propose a rationale for the role of plasma exchange therapy
for sepsis and thrombocytopenia-associated multiple organ failure.
Keywords: Sepsis, ADAMTS-13, von Willebrand factor, thrombocytopenia, multiple organ failure, plasma exchange, thrombotic microangiopathy, TAMOF
