Antithrombin and mortality in severe pneumonia patients with sepsis‐associated disseminated intravascular coagulation: an observational nationwide study: comment

Abstract

We read with interest the recent article by Tagami et al. 1.Tagami T. Matsui H. Horiguchi H. Fushimi K. Yasunaga H. Antithrombin and mortality in severe pneumonia patients with sepsis‐associated disseminated intravascular coagulation: an observational nationwide study.J Thromb Haemost. 2014; 12: 1470-9Abstract Full Text Full Text PDF PubMed Scopus (111) Google Scholar about a retrospective, large, nationwide database study of the effects of antithrombin (AT) on disseminated intravascular coagulation (DIC) in patients with severe pneumonia and sepsis‐associated DIC. This study retrospectively demonstrated that the 28‐day mortality was lower in the AT administration group than in the control group. The KyberSept trial 2.Warren B.L. Eid A. Singer P. Pillay S.S. Carl P. Novak I. Chalupa P. Atherstone A. Penzes I. Kübler A. Knaub S. Keinecke H.O. Heinrichs H. Schindel F. Juers M. Bone R.C. Opal S.M. the KyberSept Trial Study GroupHigh‐dose antithrombin in severe sepsis. A randomized controlled trial.JAMA. 2001; 286: 1869-78Crossref PubMed Scopus (1143) Google Scholar prospectively demonstrated that AT administration could not improve the mortality of patients with severe sepsis. In a subclass analysis of the KyberSept trial for DIC 3.Kienast J. Juers M. Wiedermann C.J. Hoffmann J.N. Ostermann H. Strauss R. Keinecke H.O. Warren B.L. Opal S.M. Treatment effects of high‐dose antithrombin without concomitant heparin in patients with severe sepsis with or without disseminated intravascular coagulation.J Thromb Haemost. 2006; 4: 90-7Crossref PubMed Scopus (310) Google Scholar, the mortality of the septic patients with DIC was lower in the AT group than in the control group. Gando et al. reported the validation of the scoring systems for DIC 4.Gando S. Saitoh D. Ogura H. Fujishima S. Mayumi T. Araki T. Ikeda H. Kotani J. Kushimoto S. Miki Y. Shiraishi S. Suzuki K. Suzuki Y. Takeyama N. Takuma K. Tsuruta R. Yamaguchi Y. Yamashita N. Aikawa N. for Japanese Association for Acute Medicine Sepsis Registry Study GroupA multicenter, prospective validation study of the Japanese Association for Acute Medicine disseminated intravascular coagulation scoring system in patients with severe sepsis.Crit Care. 2013; 17: R111Crossref PubMed Scopus (111) Google Scholar and then we suggested that antithrombotic therapy may worsen sepsis in the early stage of the disease while improving hemostatic abnormalities 5.Wada H. Matsumoto T. Yamashita Y. Hatada T. Is early treatment of DIC beneficial in septic patients?.Crit Care. 2014; 18: 447Crossref PubMed Scopus (4) Google Scholar. The death in DIC cases is divided into DIC‐associated and non–DIC‐associated deaths, and the former can be improved by treatment with antithrombotic therapy. The death in the patients with no recovery from DIC is termed DIC‐associated death in this letter. In a reanalysis of our previous study of sepsis 6.Takemitsu T. Wada H. Hatada T. Ohmori Y. Ishikura K. Takeda T. Sugiyama T. Yamada N. Maruyama K. Katayama N. Isaji S. Shimpo H. Kusunoki M. Nobori T. Prospective evaluation of three different diagnostic criteria for disseminated intravascular coagulation.Thromb Haemost. 2011; 105: 40-4Crossref PubMed Scopus (78) Google Scholar, a decreased AT concentration was frequently associated with a high rate of non‐recovery from DIC and a poor outcome, especially DIC‐associated death (Fig. 1), suggesting that severe AT deficiency may cause an increase in DIC‐associated death. Although antithrombotic therapy, including AT, might not improve the non–DIC‐associated deaths of DIC patients without AT deficiency, the possibility remains that AT administration to severely septic patients with DIC and AT deficiency may improve the survival outcomes. The International Society of Thrombosis and Haemostasis guidance for the diagnosis and treatment of DIC 7.Wada H. Thachil J. Di Nisio M. Mathew P. Kurosawa S. Gando S. Kim H.K. Nielsen J.D. Dempfle C.E. Levi M. Toh C.H. The Scientific Standardization Committee on DIC of the International Society on Thrombosis HaemostasisGuidance for diagnosis and treatment of DIC from harmonization of the recommendations from three guidelines.J Thromb Haemost. 2013; 11: 761-7Crossref Scopus (267) Google Scholar indicates that the administration of AT, recombinant thrombomodulin, or activated protein C may be considered in DIC patients but that further prospective evidence from randomized controlled trials confirming a benefit is required. Finally, the AT concentration is important for diagnosing DIC and for decreasing DIC‐associated deaths. T. Aota, T. Matsumoto, K. Suzuki, H. Imai, and N. Katayama analyzed references 1–5, respectively. All members discussed this letter to the editor. H. Wada wrote the letter to the editor based on the analysis. The authors state that they have no conflicts of interest. This work was supported in part by a grant‐in‐aid from the Ministry of Health, Labour and Welfare of Japan for Blood Coagulation Abnormalities and the Ministry of Education, Culture, Sports, Science and Technology of Japan.Ministry of Health, Labour and Welfare of Japan for Blood Coagulation AbnormalitiesMinistry of Education, Culture, Sports, Science and Technology of Japan