Pediatric Patients With Disseminated Intravascular Coagulation ) in α Postmarketing Surveillance of Recombinant Human Soluble Thrombomodulin ( Thrombomodulin

Recombinant human soluble thrombomodulin (thrombomodulin a [TM-a]) has been marketed as a novel anticoagulant for disseminated intravascular coagulation (DIC) in Japan since 2008. Postmarketing surveillance (PMS) has been conducted since its approval. As effectiveness and safety were not previously determined in pediatric patients, this study evaluated PMS data and examined the usefulness of TM-a in treating pediatric DIC. After excluding newborn infants, data for 210 pediatric patients were analyzed and compared to 3786 adult patients. The day after the last TM-a administration, DIC had resolved in 58.5% of the patients. At 28 days after the last TM-a administration, the survival rate was 71.6%. Nineteen episodes of adverse drug reactions were observed in 11 patients but no significant differences were noted for effectiveness and safety. Although this study was limited by its retrospective design, including selection biases and no limitation on concomitant use of other anticoagulants, TM-a appears to be useful for the treatment of DIC in both pediatric and adult patients.

[1]  J. Mimuro,et al.  Impact of recombinant soluble thrombomodulin (thrombomodulin alfa) on disseminated intravascular coagulation. , 2013, Thrombosis research.

[2]  H. Mugishima,et al.  Treatment responses for disseminated intravascular coagulation in 25 children treated with recombinant thrombomodulin: a single institution experience. , 2012, Thrombosis research.

[3]  Y. Tanigawara,et al.  Model‐Based Analysis of Covariate Effects on Population Pharmacokinetics of Thrombomodulin Alfa in Patients With Disseminated Intravascular Coagulation and Normal Subjects , 2011, Journal of clinical pharmacology.

[4]  J. Bae,et al.  Thrombin inhibits nuclear factor κB and RhoA pathways in cytokine-stimulated vascular endothelial cells when EPCR is occupied by protein C , 2009, Thrombosis and Haemostasis.

[5]  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.

[6]  M. Mohri.  ART-123. Recombinant human soluble thrombomodulin , 2006 .

[7]  H. Ören,et al.  DISSEMINATED INTRAVASCULAR COAGULATION IN PEDIATRIC PATIENTS: Clinical and Laboratory Features and Prognostic Factors Influencing the Survival , 2005, Pediatric hematology and oncology.

[8]  A. El-Nawawy,et al.  Evaluation of early detection and management of disseminated intravascular coagulation among Alexandria University pediatric intensive care patients. , 2004, Journal of tropical pediatrics.

[9]  T. Iba,et al.  [Disseminated intravascular coagulation]. , 2003, Nihon rinsho. Japanese journal of clinical medicine.

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

[11]  E. Sugimoto,et al.  The Inhibitory Effect of Recombinant Human Soluble Thrombomodulin on Initiation and Extension of Coagulation , 1999, Thrombosis and Haemostasis.

[12]  I. Maruyama.  Recombinant Thrombomodulin and Activated Protein C in the Treatment of Disseminated Intravascular Coagulation , 1999, Thrombosis and Haemostasis.

[13]  C. Enger,et al.  Acute bleeding after allogeneic bone marrow transplantation: association with graft versus host disease and effect on survival. , 1999, Transplantation.

[14]  T Maekawa,et al.  Criteria for diagnosis of DIC based on the analysis of clinical and laboratory findings in 345 DIC patients collected by the Research Committee on DIC in Japan. , 1983, Bibliotheca haematologica.

[15]  S. Lewis.  British Committee for Standards in Haematology , 1969 .