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.