Bleeding events associated with recombinant human soluble thrombomodulin, classified according to renal function, in sepsis-induced disseminated intravascular coagulation

• Published in: International journal of clinical pharmacology and therapeutics Vol. 61; no. 7; pp. 297 - 305
• Main Authors: Onoda, Toshihisa, Aoyama, Koichi, Suzuki, Mikana, Matsumoto, Takahiro, Tanaka, Hiroyuki, Ishii, Toshihiro
• Format: Journal Article
• Language: English
• Published: Germany Dustri - Verlag Dr. Karl Feistle GmbH & Co. KG 01.07.2023
• Subjects: Disseminated Intravascular Coagulation - diagnosis; Disseminated Intravascular Coagulation - drug therapy; Disseminated Intravascular Coagulation - etiology; Hemorrhage; Humans; Kidney - physiology; Recombinant Proteins - adverse effects; Sepsis; Sepsis - complications; Sepsis - drug therapy; Thrombomodulin - therapeutic use; Treatment Outcome
• ISSN: 0946-1965
• DOI: 10.5414/CP204362

Recombinant human soluble thrombomodulin (rhsTM) is a therapeutic agent for sepsis-induced disseminated intravascular coagulation (DIC) and is associated with bleeding events. rhsTM is a renal excretion drug; however, information on the role of rhsTM in renal function is limited. In this retrospective observational study, we assessed rhsTM-associated bleeding events according to the renal function of patients with sepsis-induced DIC. We analyzed the data of 79 patients administered a standard-dose of rhsTM for sepsis-induced DIC, at a single center. Patients were classified based on estimated glomerular filtration rate (eGFR). We measured fresh bleeding events following rhsTM administration, DIC score efficacy, and 28-day mortality. Fresh bleeding events were observed in 15 patients, with a significant difference in the eGFR, platelet count, and DIC scores. Furthermore, fresh bleeding events tended to increase with the deterioration of renal function (p = 0.039). The DIC scores in all renal function groups decreased after -rhsTM administration. Additionally, the 28-day mortality was less than 30% in all groups. Our results indicate that the effectiveness of the standard-dose of rhsTM is not related to renal function. However, standard-dose rhsTM therapy could potentially increase the risk of adverse bleeding events with severe renal function equivalent to G5.