Sepsis-related coagulopathy treatment based on the disseminated intravascular coagulation diagnostic criteria: a post-hoc analysis of a prospective multicenter observational study
Authors: Wada Takeshi , Yamakawa Kazuma , Kabata Daijiro , Abe Toshikazu , Fujishima Seitaro , Kushimoto Shigeki , Mayumi Toshihiko , Ogura Hiroshi , Saitoh Daizoh , Shiraishi Atsushi , Otomo Yasuhiro , Gando Satoshi ,   the JAAM FORECAST Group, Sasaki Junichi , Kotani Joji , Takeyama Naoshi , Tsuruta Ryosuke , Takuma Kiyotsugu , Yamashita Norio , Shiraishi Shin-ichiro , Ikeda Hiroto , Shiino Yasukazu , Tarui Takehiko , Nakada Takaaki , Hifumi Toru , Okamoto Kohji , Sakamoto Yuichiro , Hagiwara Akiyoshi , Masuno Tomohiko , Ueyama Masashi , Fujimi Satoshi , Umemura Yutaka , Mizobata Yasumitsu , Yamada Yasuo , Sugiyama Satoru , Ishida Hiroshi , Narimatsu Eichi , Miyasho Koji , Kanai Toshio , Miyatake Satoru , Iiduka Ryouji , Imamura Hiroshi , Mizushima Yasuaki , Sato Yoshitake , Nemoto Manabu , Hanada Hiroyuki , Shichinohe Yasuo , Hirahara Kenji , Kon Akihide , Sugita Manabu , Naoe Yasutaka , Kirita Manabu , Sadamitsu Daikai , Yoshida Masahiro 
Published: March 2023

Background

The development of disseminated intravascular coagulation (DIC) in patients with sepsis has been repeatedly confirmed as a factor associated with poor prognosis. Anticoagulant therapy has been expected to improve sepsis patient outcomes, whereas no randomized controlled trials have demonstrated the survival benefit of anticoagulant therapies in non-specific overall sepsis. Patient selection based on the component of “high disease severity” in addition to “sepsis with DIC” has recently proved important in identifying appropriate targets for anticoagulant therapy. The aims of this study were to characterize “severe” sepsis DIC patients and to identify the patient population benefiting from anticoagulant therapy.

Methods

This retrospective sub-analysis of a prospective multicenter study included 1,178 adult patients with severe sepsis from 59 intensive care units in Japan from January 2016 to March 2017. We examined the association of patient outcomes, including organ dysfunction and in-hospital mortality, with the DIC score and prothrombin time-international normalized ratio (PT-INR), one of the components of the DIC score, using multivariable regression models including the cross-product term between these indicators. Multivariate Cox proportional hazard regression analysis with non-linear restricted cubic spline including a three-way interaction term (anticoagulant therapy × the DIC score × PT-INR) was also performed. Anticoagulant therapy was defined as the administration of antithrombin, recombinant human thrombomodulin, or their combination.

Results

In total, we analyzed 1013 patients. The regression model showed that organ dysfunction and in-hospital mortality deteriorated with higher PT-INR values in the range of < 1.5 and that this trend was more pronounced with higher DIC scores. Three-way interaction analysis demonstrated that anticoagulant therapy was associated with better survival outcome in patients with a high DIC score and high PT-INR. Furthermore, we identified a DIC score ≥ 5 and PT-INR ≥ 1.5 as the clinical threshold for identification of optimal targets for anticoagulant therapy.

Conclusions

The combined use of the DIC score and PT-INR helps in selecting the optimal patient population for anticoagulant therapy in sepsis-induced DIC. The results obtained from this study will provide valuable information regarding the study design of randomized controlled trials examining the effects of anticoagulant therapy for sepsis.

Trial registration: UMIN-CTR, UMIN000019742. Registered on November 16, 2015.