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K. Abeyama, D. M. Stern, Y. Ito, K. Kawahara, Y. Yoshimoto, M. Tanaka, T. Uchimura, N. Ida, Y. Yamazaki, S. Yamada, Y. Yamamoto, H. Yamamoto, S. Iino, N. Taniguchi and I. Maruyama, “The N-Terminal Domain of Thrombomodulin Sequesters High-Mobility Group-B1 Protein, a Novel Antiinflammatory Mechanism,” Journal of Clinical Investigation, Vol. 115, No. 5, 2005, pp. 1267-1274.

has been cited by the following article:

• TITLE: The Concept Study of Recombinant Human Soluble Thrombomodulin in Patients with Acute Respiratory Distress Syndrome

  AUTHORS: Kenji Tsushima, Toshiki Yokoyama, Tomonobu Koizumi, Keishi Kubo, Koichiro Tatsumi

  KEYWORDS: Acute Respiratory Distress Syndrome; Recombinant Human Soluble Thrombomodulin; Thrombin-Antithrombin Complex; SpO2/FIO2; High-Mobility Group-1

  JOURNAL NAME: International Journal of Clinical Medicine, Vol.4 No.11, November 15, 2013

  ABSTRACT: Background: Recombinant human soluble thrombomodulin (rhTM) was approved for the treatment of disseminated intravascular coagulation in Japan, and rhTM has anti-inflammatory effects. Disordered coagulation is a part of the acute respiratory distress syndrome (ARDS) pathophysiology and thus we hypothesize that anticoagulant therapy may help. This preliminary study was to observe the safety of rhTM administration and the improvement on biomarker levels after the therapy for ARDS-patients. Objectives: Case series of ARDS-patients. Methods: Seventeen ARDS-patients that required ventilatory management were treated with rhTM and clinical and laboratory data were collected including platelets, thrombin-antithrombin complex (TAT), fibrinogen degradation products, oxygen saturation/the fraction of inspired oxygen (SpO2/FIO2), and high-mobility group-1 (HMG-1). The administration of rhTM was started during 6 days at a bolus dose of 0.06 mg/kg/day immediately after the diagnosis of ARDS. Results: Eleven of the 17 ARDS-patients were alive at 28 days after the beginning of the administration of rhTM. The serial pattern of the SpO2/FIO2 showed remarkable differences between the survivors and nonsurvivors from day 5 to day 7. The TAT in the survivors significantly decreased after treatment, and there were significantly lower levels in the TAT on day 7 in comparison to that of the nonsurvivors. The serial changes of HMG-1 showed increased levels in the nonsurvivors until day 5 after the administration of rhTM. Conclusions: Additional rhTM administration can safely improve the parameters in survival ARDS-patients, as demonstrated by significant improvements in the SpO2/FIO2, HMG-1 and TAT.