Efficacy of Combined Thrombomodulin and Antithrombin in Anticoagulant Therapy for Acute Cholangitis-induced Disseminated Intravascular Coagulation

Abstract

Objective The efficacy and safety of concomitant use of antithrombin (AT) with recombinant human soluble thrombomodulin (rTM) for acute cholangitis-induced disseminated intravascular coagulation (AC-induced DIC) remains unclear. This study was conducted to investigate the efficacy of AT combined with rTM as anticoagulant therapy for AC-induced DIC. Methods One hundred patients with AC-induced DIC received anticoagulant therapy using rTM from April 2010 to December 2017. Of the 83 patients treated with rTM immediately after the diagnosis of DIC, excluding those who had not undergone biliary drainage or who had malignancies or a serum AT III level >70%, 56 patients were studied. Outcomes and adverse events (AEs) were retrospectively compared between the 16 patients treated with rTM alone (rTM group) and the 40 patients treated with rTM and AT (rTM+AT group). Results Patients' background characteristics did not differ markedly, except for a significantly higher serum D-dimer level in the rTM group than in the rTM+AT group (p=0.038). The DIC resolution rates on day 9 were 100% and 95.1% in the rTM and rTM+AT groups, respectively (p=0.909). The mean DIC scores were significantly lower in the rTM group than in the rTM+AT group on days 3 (p=0.012), 5 (p<0.001), 7 (p=0.033), and 9 (p=0.007). The incidence of AEs was 6.3% and 10.0% (p=0.941), and the in-hospital mortality rates was 0% and 5.0% (p=0.909) in the rTM and rTM+AT groups, respectively. Conclusion The concomitant use of AT with anticoagulant therapy using rTM for AC-induced DIC may not help improve the treatment outcome.

Keywords: acute cholangitis; antithrombin; biliary drainage; disseminated intravascular coagulation; thrombomodulin.

Figure 1.

Flowchart of the selection of patient groups. DIC: disseminated intravascular coagulation, AC: acute cholangitis, rTM: recombinant human soluble thrombomodulin, AT: antithrombin

Figure 2.

A comparison of the mean values of the DIC score between the rTM and rTM+AT groups. ^ap<0.05 vs. rTM+AT group; ^cp<0.05 vs. baseline. DIC: disseminated intravascular coagulation, rTM: recombinant human soluble thrombomodulin, AT: antithrombin, SD: standard deviation

Figure 3.

A comparison of the mean values of the SIRS score between the rTM and rTM+AT groups. ^cp<0.05 vs. baseline. SIRS: systemic inflammatory response syndrome, rTM: recombinant human soluble thrombomodulin, AT: antithrombin, SD: standard deviation

Figure 4.

A comparison of mean values of serum parameters between the rTM and rTM+AT groups. ^ap<0.05 vs. rTM+AT group; ^cp<0.05 vs. baseline. Plt: platelet count, PT-INR: prothrombin time-international normalized ratio, ATIII: antithrombin III, T-bil: total bilirubin, CRP: C-reactive protein, rTM: recombinant human soluble thrombomodulin, AT: antithrombin, SD: standard deviation