Successful treatment of pneumonia-induced severe ARDS complicated with DIC in two infants using recombinant human thrombomodulin

Severe acute respiratory distress syndrome (ARDS) complicated with disseminated intravascular coagulopathy (DIC) is a life-threatening disease in childhood for which there is few confirmed therapeutic strategies. Recombinant human soluble thrombomodulin (rhTM) has been widely used for the treatment of DIC as an anticoagulant agent. In addition to anti-DIC effects, recent evidences demonstrated that rhTM could improve ARDS in adult patients via anti-inflammatory effects. On the other hand, the safety and efficacy of rhTM on pediatric ARDS with or without DIC are unclear. In this preliminary study, we administered rhTM for 6 days to two infants with pneumonia-induced severe ARDS (PaO2/FiO2 ratio ≤ 100 mmHg) with DIC, and investigated clinical course and changes in biochemical markers. After administration of rhTM, clinical symptoms and laboratory data improved in both infants and there was no adverse effect of rhTM. The infants were successfully treated and discharged without any complications.

[1]  B. Suberviola,et al.  Microbiological Diagnosis of Sepsis: Polymerase Chain Reaction System Versus Blood Cultures. , 2016, American journal of critical care : an official publication, American Association of Critical-Care Nurses.

[2]  Christopher L. Carroll,et al.  Pediatric acute respiratory distress syndrome: consensus recommendations from the Pediatric Acute Lung Injury Consensus Conference. , 2015, Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.

[3]  H. Yuhara,et al.  Recombinant human soluble thrombomodulin in severe sepsis: a systematic review and meta‐analysis , 2015, Journal of thrombosis and haemostasis : JTH.

[4]  J. Mimuro,et al.  Postmarketing Surveillance of Recombinant Human Soluble Thrombomodulin (Thrombomodulin α) in Pediatric Patients With Disseminated Intravascular Coagulation , 2014, Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis.

[5]  J. Mimuro,et al.  Recombinant soluble human thrombomodulin (thrombomodulin alfa) in the treatment of neonatal disseminated intravascular coagulation , 2014, European Journal of Pediatrics.

[6]  K. Kubo,et al.  The Concept Study of Recombinant Human Soluble Thrombomodulin in Patients with Acute Respiratory Distress Syndrome , 2013 .

[7]  T. Shimazu,et al.  Recombinant human soluble thrombomodulin in sepsis-induced disseminated intravascular coagulation: a multicenter propensity score analysis , 2013, Intensive Care Medicine.

[8]  S. Madhi,et al.  The Burden of Childhood Pneumonia in the Developed World: A Review of the Literature , 2012, The Pediatric infectious disease journal.

[9]  Arthur S Slutsky,et al.  Acute Respiratory Distress Syndrome The Berlin Definition , 2012 .

[10]  T. Shimazu,et al.  Recombinant human soluble thrombomodulin improves mortality and respiratory dysfunction in patients with severe sepsis , 2012, The journal of trauma and acute care surgery.

[11]  M. Shimaoka,et al.  Thrombomodulin: A Bifunctional Modulator of Inflammation and Coagulation in Sepsis , 2012, Critical care research and practice.

[12]  Tsukasa Nakamura,et al.  Increased levels of soluble receptor for advanced glycation end products (sRAGE) and high mobility group box 1 (HMGB1) are associated with death in patients with acute respiratory distress syndrome. , 2011, Clinical biochemistry.

[13]  C. Chung,et al.  Pathogenesis of indirect (secondary) acute lung injury , 2011, Expert review of respiratory medicine.

[14]  A. Mantovani,et al.  Elevated plasma and alveolar levels of soluble receptor for advanced glycation endproducts are associated with severity of lung dysfunction in ARDS patients. , 2010, The Tohoku journal of experimental medicine.

[15]  A. Randolph.  Management of acute lung injury and acute respiratory distress syndrome in children. , 2009, Critical care medicine.

[16]  S. Yamada,et al.  Proteolytic Cleavage of High Mobility Group Box 1 Protein by Thrombin–Thrombomodulin Complexes , 2008, Arteriosclerosis, thrombosis, and vascular biology.

[17]  Academisch Proefschrift,et al.  Pediatric acute lung injury. , 2007, Paediatric respiratory reviews.

[18]  D. Foell,et al.  Mechanisms of Disease: a 'DAMP' view of inflammatory arthritis , 2007, Nature Clinical Practice Rheumatology.

[19]  N. Aoki,et al.  Efficacy and safety of recombinant human soluble thrombomodulin (ART‐123) in disseminated intravascular coagulation: results of a phase III, randomized, double‐blind clinical trial , 2007, Journal of thrombosis and haemostasis : JTH.

[20]  Diane P. Martin,et al.  Incidence and outcomes of acute lung injury. , 2005, The New England journal of medicine.

[21]  F B Taylor,et al.  Towards Definition, Clinical and Laboratory Criteria, and a Scoring System for Disseminated Intravascular Coagulation , 2001, Thrombosis and Haemostasis.

[22]  K. Tracey,et al.  Cutting Edge: HMG-1 as a Mediator of Acute Lung Inflammation1 , 2000, The Journal of Immunology.

[23]  K. Tracey,et al.  HMG-1 as a late mediator of endotoxin lethality in mice. , 1999, Science.

[24]  U E Ruttimann,et al.  The Pediatric Risk of Mortality III--Acute Physiology Score (PRISM III-APS): a method of assessing physiologic instability for pediatric intensive care unit patients. , 1997, The Journal of pediatrics.

[25]  R. A. Castillo-Lara,et al.  Definitions for sepsis and organ failure. , 1993, JAMA.