A retrospective comparative study of recombinant human thrombomodulin and gabexate mesilate in sepsis-induced disseminated intravascular coagulation patients

Abstract

The novel biological agent recombinant human thrombomodulin (rhTM) has been used clinically in Japan to treat disseminated intravascular coagulation (DIC) since 2008.Previous studies have shown the efficacy of rhTM versus heparin therapy or non-rhTM therapy. We retrospectively evaluated and compared the efficacies of rhTM and gabexate mesilate (GM) in patients diagnosed with sepsis-induced DIC. From September 2010 to October 2012, patients with sepsis-induced DIC who were treated with rhTM (n = 13) or GM (n = 10) at Nagasaki Municipal Hospital were extracted.Patients receiving other anticoagulants in combination were excluded. Clinical information, laboratory data, Sequential Organ Failure Assessment (SOFA) scores, and DIC scores were obtained from the medical records. Mortality at days 7 and 30 after DIC diagnosis and changes in laboratory data and SOFA scores from days 1-7 were evaluated. The groups' clinical characteristics did not differ, except for the relatively higher C-reactive protein (CRP) levels in the rhTM group (P = 0.0508). The survival rates of the rhTM and GM groups on days 7 and 30 were 92.3%, 69.2% and 80%, 70%, respectively, both group indicated similar mortality. However, on day 7, the platelet counts, SOFA scores, and CRP levels significantly improved in the rhTM group; the platelet counts and SOFA scores did not improve significantly in the GM group. The 4 platelet counts of the rhTM group significantly improved compared to the GM group (P=0.004). Recombinant human thrombomodulin might be more effective for sepsis-induced DIC than GM.

Pharmacokinetics of recombinant human soluble thrombomodulin in disseminated intravascular coagulation patients with acute renal dysfunction

“…Recently, the clinical effects of ART-123 in patients with sepsisinduced DIC were reported (9)(10)(11)(12)(13)(14). In our multicentre, retrospective, large-scale study, 45 % of sepsis-induced DIC patients treated with ART-123 had undergone renal replacement therapy (12).…”

Successful treatment of disseminated intravascular coagulation by recombinant human soluble thrombomodulin in patients with acute myeloid leukemia

“…Previous studies have reported that these resolution rates were 55.1% (n = 216) and 57.8% (n = 135), respectively, [ 17 ] thus at our institution, the DIC resolution rates were markedly better than that previously reported. For infectious diseases, some reports indicated that rTM was more effective [ 20 , 23 ] and that it significantly reduced mortality and increased survival compared with GM. [ 22 , 30 , 31 ] In the setting of hematologic malignancies, Takezako et al revealed that OS was superior in AML patients treated with rTM when compared with heparin.…”

“…Gabexate mesilate (GM), a synthetic protease inhibitor (SPI), was previously used routinely for treating DIC before rTM was approved in Japan, although no clinical trials have been reported assessing its efficacy for treating DIC. [ 20 ] Recent studies have indicated that rTM is more effective than GM for treating DIC in patients with infectious diseases; [ 21 – 23 ] conversely, little research has been conducted among AML patients. Therefore, we retrospectively evaluated the efficacy of rTM compared to that of GM for treating AML patients complicated with DIC.…”

Efficacy of recombinant human soluble thrombomodulin in patients with sepsis and disseminated intravascular coagulation in the gastroenterology field

“…Takazono et al (12) evaluated and compared the clinical efficacies of rTM and GM for the treatment of sepsis-induced DIC. In that study, the platelet counts of the rTM group significantly improved compared to the GM group.…”