Abstract
BackgroundAlthough recombinant human soluble thrombomodulin (rTM) has been widely used to treat disseminated intravascular coagulation (DIC) in Japan, there is no consensus regarding rTM efficacy. Therefore, if the factors influencing rTM efficacy is revealed, it may be possible to demonstrate the effectiveness of rTM by limiting the patients who use rTM. This study investigated the factors of rTM treatment which influence DIC status.MethodsThis retrospective case-control study enrolled hospitalized adult patients treated with rTM from October 2010 to May 2020. Among these patients, 227 who were diagnosed with DIC according to the Japanese Association for Acute Medicine DIC scoring system were assessed. The primary endpoint was the 28-day mortality after rTM treatment. For Cox-proportional hazards model, explanatory factors determined using univariate analysis with p < 0.1 were used. In addition, some factors considered to affect DIC-related mortality such as age ≥ 75 years, rTM dose ≥380 U/kg, antithrombin III treatment, and diseases with a poor prognosis (sepsis, solid tumors, and trauma) were added as covariates.ResultsUnivariate analyses suggested that male sex (p = 0.029), treatment in intensive care unit (p = 0.061), and prothrombin time-international normalized ratio (PT-INR) (p < 0.001) were the factors influencing DIC-related 28-day mortality after rTM treatment. According to Cox-proportional hazard analysis, the adjusted odds ratio for DIC-related 28-day mortality in patients with PT-INR ≥ 1.67 was 2.23 (95% confidence interval: 1.451–3.433, p < 0.001), age ≥ 75 years was 1.57 (95% confidence interval: 1.009–2.439, p = 0.046), and male sex was 1.66 (95% confidence interval: 1.065–2.573, p = 0.025), respectively. As life-threatening bleeding events were not observed, prolonged PT-INR might directly or indirectly affect DIC-related mortality caused by rTM treatment.ConclusionrTM treatment for DIC was less effective in male patients with PT-INR ≥ 1.67 and age ≥ 75 years.
Highlights
Recombinant human soluble thrombomodulin has been widely used to treat disseminated intravascular coagulation (DIC) in Japan, there is no consensus regarding recombinant human soluble thrombomodulin (rTM) efficacy
Saito et al [5] revealed no significant differences in DIC resolution rates following rTM treatment and heparin treatment; they demonstrated that bleeding events following rTM treatment were lower than following heparin treatment
Univariate analysis revealed that male sex (p = 0.029), treatment in Intensive care unit (ICU) (p = 0.061), and prothrombin time-international normalized ratio (PT-INR) (p < 0.001) are possible factors influencing DIC-related 28-day mortality after rTM treatment (Table 2)
Summary
Recombinant human soluble thrombomodulin (rTM) has been widely used to treat disseminated intravascular coagulation (DIC) in Japan, there is no consensus regarding rTM efficacy. If the factors influencing rTM efficacy is revealed, it may be possible to demonstrate the effectiveness of rTM by limiting the patients who use rTM. Recombinant human soluble thrombomodulin (rTM), a novel anticoagulant, has been widely used to improve DIC status in Japan [5,6,7]. RTM treatment is highly effective and safe according to many studies [5,6,7], a randomized, double-blind, multinational, multicenter phase 3 study (SCARLET Randomized Clinical Trial) has reported no significant differences in 28-day mortality rate following rTM therapy and that following placebo therapy [8]. Revealing the factors influencing rTM efficacy may help in demonstrating the effectiveness of rTM by limiting the patients receiving rTM
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