title: Treatment responses for disseminated intravascular coagulation in 25 children treated with recombinant thrombomodulin: a single institution experience.
abstract: BACKGROUND
  Recombinant thrombomodulin (rTM), which degrades factors Va and VIIIa by activating protein C, has been developed as a new drug for treating disseminated intravascular coagulation (DIC).
  
  
  METHODS
  Since July 2009, we have treated 25 children with DIC using rTM (380 U/kg/day, or 130 U/kg/day for newborns) as a first-line therapy. Median duration of rTM administration was 5 consecutive days (range, 2-13 days). We employed DIC criteria of the Japan Welfare and Health Ministry. The first day on which rTM treatment was given was defined as day 1.
  
  
  RESULTS
  Median patients age was 3 years. Underlying diseases were hematological disorders (n=13) and severe infection (n=12). Overall, 20 of the 25 patients had recovered from DIC by day 7 and 22 of the 25 patients remained alive at day 28. Median Pediatric Logistic Organ Dysfunction score improved from 11 on day 1 to 2 on day 7 (p=0.009). Laboratory data (median) on day 7 (prothrombin time (PT) ratio, 1.15; fibrin and fibrinogen degradation products (FDP), 9.6 mg/l; D-dimer, 1.6 mg/l FEU; antithrombin, 112%; protein C, 105%) were significantly improved compared to results on day 1 (PT ratio, 1.39; FDP, 21.6 mg/l; D-dimer, 6.4 mg/l FEU; antithrombin, 86%; protein C, 54%). Whereas, 5 patients failed to respond and serious bleeding events were observed in 2 newborns.
  
  
  CONCLUSIONS
  The efficacy of rTM cannot be assessed from the present dataset, due to several limitations such as the small heterogenous patient cohort, and the lack of age- and disease-matched controls. Nevertheless, this case-series remains important in terms of enabling further prospective control studies to evaluate the efficacy of rTM in children.
authors.affiliation: Department of Pediatrics, School of Medicine, Nihon University, Tokyo, Japan. yagasaki@med.nihon-u.ac.jp
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yagasaki
authors.forename: Maiko
authors.initials: M
authors.lastname: Kato
authors.forename: Katsuyoshi
authors.initials: K
authors.lastname: Shimozawa
authors.forename: Maiko
authors.initials: M
authors.lastname: Hirai
authors.forename: Eri
authors.initials: E
authors.lastname: Nishikawa
authors.forename: Hirotsugu
authors.initials: H
authors.lastname: Okuma
authors.forename: Wakako
authors.initials: W
authors.lastname: Ishii
authors.forename: Yuki
authors.initials: Y
authors.lastname: Imai
authors.forename: Masaharu
authors.initials: M
authors.lastname: Matsumura
authors.forename: Ryuta
authors.initials: R
authors.lastname: Yonezawa
authors.forename: Kayo
authors.initials: K
authors.lastname: Yoshikawa
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Shichino
authors.forename: Motoaki
authors.initials: M
authors.lastname: Chin
authors.forename: Hideo
authors.initials: H
authors.lastname: Mugishima
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D004211:Disseminated Intravascular Coagulation / Q000097:blood / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D011994:Recombinant Proteins / Q000627:therapeutic use; D012189:Retrospective Studies; D018180:Thrombomodulin / Q000627:therapeutic use*
chemical_list: D011994:Recombinant Proteins; D018180:Thrombomodulin