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.

Clinical Outcomes of Early Endoscopic Transpapillary Biliary Drainage for Acute Cholangitis Associated with Disseminated Intravascular Coagulation

“…A selection may have caused bias in the endoscopic procedures, such as EST, stone removal, and the method of EBD, because the endoscopic procedures were left to the discretion of the attending endoscopist. Treatment outcomes may be affected by anticoagulant therapy and antibiotics [14,15,24,25]. Furthermore, this study used a retrospective design, and the number of patients was small because of the rare nature of the subject disease, thereby indicating that a large-scale, prospective study is necessary to confirm our findings.…”

“…In this study, treatment outcomes may be affected by anticoagulant therapy. However, only a few reports on anticoagulant therapy for AC-induced DIC exist [14,15,24,25], so very little evidence exists that can form a basis for the selection of anticoagulant agents for this condition.…”

The Necessity of Individualized Treatment for Sepsis-Associated Disseminated Intravascular Coagulation by Infected Organ

“…A study on the efficacy of AT supplementation in combination with rTM preparation in 2019 reported that the concomitant use of AT with rTM for acute cholangitis-induced DIC may not improve treatment outcomes. 22 A multicenter study evaluating the clinical effectiveness of rTM in 284 patients with acute cholangitis and sepsis-induced DIC who underwent biliary drainage 23 concluded that after propensity score matching, the 28-day survival rate was significantly higher in the rTM group when compared with the non-rTM group. Thus far, many reports have suggested the usefulness of rTM preparations in patients with septic DIC caused by biliary tract infection.…”

Clinical impact of recombinant thrombomodulin administration on disseminated intravascular coagulation due to severe acute cholangitis (Recover‐AC study)

“…To date, only a few reports have evaluated the treatment of DIC caused by acute cholangitis. 11,12,20 Suetani et al 12 evaluated the role of rhTM in the treatment of DIC caused by acute cholangitis. Among the 66 patients evaluated (rhTM group, n = 36, non-rhTM group, n = 30), the DIC resolution rate on day 9 was statistically significantly higher in the rhTM group compared with the control group (83.3% vs 52.8%, P < .01).…”

“…6 Recombinant thrombomodulin (rhTM) is available in Japan and is potentially effective in the treatment of DIC. 10 Several studies related to drugs for the treatment of acute cholangitis have shown negative results in improvement of overall survival (OS) with rhTM, 11,12 and the evidence in this field is still insufficient. However, as mentioned above, biliary drainage might be technically feasible in almost all patients.…”