Use of Antithrombin and Thrombomodulin in the Management of Disseminated Intravascular Coagulation in Patients with Acute Cholangitis

Abstract

Background/AimsTo evaluate the usefulness and safety of treating disseminated intravascular coagulation (DIC) complicating cholangitis primarily with antithrombin (AT) and thrombomodulin (rTM).MethodsA DIC treatment algorithm was determined on the basis of plasma AT III levels at the time of DIC diagnosis and DIC score changes on treatment day 3. Laboratory data and DIC scores were assessed prospectively at 2-day intervals.ResultsDIC reversal rates >75% were attained on day 7. In the DIC reversal group, statistically significant differences from baseline were observed in interleukin-6 and C-reactive protein levels within 5 days. Patients with no DIC score improvements after treatment with AT alone experienced slow improvement on a subsequent combination therapy with rTM. Although a subgroup with biliary drainage showed greater improvement in DIC scores than did the nondrainage subgroup, the mean DIC score showed improvement even in the nondrainage subgroup alone. Gastric cancer bleeding that was treated conservatively occurred in one patient. As for day 28 outcomes, three patients died from concurrent malignancies.ConclusionsAlthough this algorithm was found to be useful and safe for DIC patients with cholangitis, it may be better to administer rTM and AT simultaneously from day 1 if the plasma AT III level is less than 70%.

Tokyo Guidelines 2018: initial management of acute biliary infection and flowchart for acute cholangitis

“…Although these anticoagulants have been well studied, including in RCTs, the numbers of cholangitis patients in these studies are either unknown or very small, and the value of anticoagulants in severe cholangitis is unclear. Two studies have reported the value of recombinant human soluble thrombomodulin (rTM) for DIC in patients with acute cholangitis (CS) . Suetani et al divided 66 patients diagnosed with acute cholangitis‐induced DIC on the basis of the TG13 diagnostic criteria into 33 who were treated with rTM and 36 who were not, and found that the DIC resolution rate was significantly better in patients given rTM (83.3% vs. 52.8%, P < 0.01), but that there was no significant difference in mortality (13.3% vs. 27.8%, P = 0.26) (CS) .…”

“…Suetani et al divided 66 patients diagnosed with acute cholangitis‐induced DIC on the basis of the TG13 diagnostic criteria into 33 who were treated with rTM and 36 who were not, and found that the DIC resolution rate was significantly better in patients given rTM (83.3% vs. 52.8%, P < 0.01), but that there was no significant difference in mortality (13.3% vs. 27.8%, P = 0.26) (CS) . In a study by Nakahara et al of 13 patients with acute cholangitis‐induced DIC, seven patients who were treated with rTM had significantly lower DIC scores compared with six who were only treated with antithrombin III (CS) . Both those studies were case series with insufficient numbers of patients to provide more than a low level of evidence, but as there were no serious side‐effects, the use of rTM in patients with severe cholangitis complicated by DIC may be considered.…”

Efficacy of antithrombin in preclinical and clinical applications for sepsis-associated disseminated intravascular coagulation

“…However, the Japanese health-care system allows the use of 3,000 IU/day of AT only in limited, severe cases. Thus, combination therapy with AT and recombinant thrombomodulin is now attracting attention [ 43 ].…”

IL‐7 and procalcitonin are useful biomarkers in the comprehensive evaluation of the severity of acute cholangitis

“…Acute cholangitis is established by cholangiovenous reflux, in which the bacteria and/or endotoxins subsequently flow into the blood due to increased pressure in the biliary duct . As this process becomes severe, BTI is often accompanied by DIC, septic shock, and organ failure . In the present study, 39.3% of the patients were diagnosed as having DIC and the 28‐day mortality rate was 20.8% in patients with DIC.…”

“…IL‐6, IL‐10, and MCP‐1 showed correlation coefficients of >0.7 (Table ). We therefore selected IL‐6 as the variable to be used in the subsequent multivariate analysis because it was the most important and useful clinical factor among these cytokines and chemokines in acute cholangitis and DIC . IL‐7 was the predictor of acute cholangitis with DIC in the multivariate analysis (Table ).…”