Efficacy and safety of anticoagulant therapy in three specific populations with sepsis: a meta‐analysis of randomized controlled trials: reply

Abstract

We thank Professor Wada and colleagues for their valuable and insightful comments regarding the significance of disseminated intravascular coagulation (DIC) diagnosis in sepsis as it applies to our systematic review article. The major findings of our article 1.Umemura Y. Yamakawa K. Ogura H. Yuhara H. Fujimi S. Efficacy and safety of anticoagulant therapy in three specific populations with sepsis: a meta‐analysis of randomized controlled trials.J Thromb Haemost. 2016; 14: 518-30Crossref PubMed Scopus (115) Google Scholar can be summarized as follows; (i) anticoagulant therapy for the overall population with sepsis has no survival benefit with an increased risk of bleeding complications, but (ii) anticoagulant therapy for the population with sepsis‐induced DIC is expected to improve mortality. Interestingly, we also found that the treatment effect for the sepsis population with a single coagulation‐related parameter disorder was not favorable. These findings suggest that for the purpose of accurately assessing the pathophysiological and coagulopathic conditions in sepsis patients, we need to evaluate the patients by some DIC diagnostic criteria that consist of several laboratory parameters and clinical signs, such as the International Society on Thrombosis and Haemostasis (ISTH) overt DIC criteria and the Japanese Association for Acute Medicine (JAAM) DIC criteria, not by a single coagulation parameter. Which DIC diagnostic criterion is the most useful for decision‐making regarding anticoagulant therapy in sepsis patients? As Wada et al. mentioned in their letter, each diagnostic criterion was established for different purposes and has different strengths and limitations for diagnosis of DIC 2.Wada H. Thachil J. Di Nisio M. Kurosawa S. Gando S. Toh C.H. Scientific and Standardization Committee on DIC of the International Society on Thrombosis and HaemostasisHarmonized guidance for disseminated intravascular coagulation from the International Society on Thrombosis and Haemostasis and the current status of anticoagulant therapy in Japan: a rebuttal.J Thromb Haemost. 2013; 11: 2078-9Crossref PubMed Scopus (17) Google Scholar, 3.Wada H. Asakura H. Okamoto K. Iba T. Uchiyama T. Kawasugi K. Koga S. Mayumi T. Koike K. Gando S. Kushimoto S. Seki Y. Madoiwa S. Maruyama I. Yoshioka A. Japanese Society of Thrombosis Hemostasis/DIC subcommitteeExpert consensus for the treatment of disseminated intravascular coagulation in Japan.Thromb Res. 2010; 125: 6-11Abstract Full Text Full Text PDF PubMed Scopus (169) Google Scholar. Although these diagnostic criteria aim to decide the indications and optimal timing for anticoagulant therapy in patients with sepsis, it is difficult to evaluate the superiority of one criterion over the others using predictive values for mortality. Recently, we performed a post hoc subgroup analysis of a multicenter nationwide retrospective cohort study, named the Japan Septic Disseminated Intravascular Coagulation (J‐Septic DIC) registry, in 42 intensive care units in Japan 4.Yamakawa K. Umemura Y. Hayakawa M. Kudo D. Sanui M. Takahashi H. Yoshikawa Y. Hamasaki T. Fujimi S. for the Japan Septic Disseminated Intravascular Coagulation (J‐Septic DIC) study groupBenefit profile of anticoagulant therapy in sepsis: a nationwide multicentre registry in Japan.Crit Care. 2016; 20: 229Crossref PubMed Scopus (67) Google Scholar. In this large database study, treatment effect of anticoagulant therapy in the ISTH overt DIC‐diagnosed patients (adjusted hazard ratio [95% confidence interval], 0.609 [0.456–0.814]) was similar to that in the JAAM DIC‐diagnosed patients (0.685 [0.559–0.839]). The results of this registry study were comparable to those of our systematic review, in which mortality reductions were not different between the DIC criteria. Taken together, these findings suggested that the efficacy of anticoagulant therapy for sepsis‐induced DIC was likely to be similar regardless of the DIC criteria and we might use any DIC criteria for determining the indication for anticoagulant therapy. However, we recognized that the design of our study was not sufficient to address the definitive evidence for the indications for anticoagulant therapy in sepsis. Further investigations are required. Finally, again, we thank Professor Wada and colleagues for their insightful comments and providing their valuable data. Although we have insufficient clinical data for the efficacy of anticoagulant therapy in sepsis‐induced DIC so far, we expect future randomized controlled trials of anticoagulant therapy targeting specific sepsis populations such as those with DIC, as well as the revival of discussion about anticoagulant interventions for sepsis. The authors state that they have no conflict of interest.