Recombinant human soluble thrombomodulin improves mortality in patients with sepsis especially for severe coagulopathy: a retrospective study

Kato, Takahiro; Matsuura, Keiichi

doi:10.1186/s12959-018-0172-6

Cited by 10 publications

(7 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Hayakawa et al demonstrated that AT treatment in sepsis-induced DIC may be associated with a reduced in-hospital all-cause mortality [140]. Similarly a study be Kato et al suggested possible mortality benefit in septic patients with coagulopathy treated with recombinant thrombomodulin [141]. Although none of the studies with anticoagulants provide data as robust as the PROWESS trial studying activated protein C (APC), the benefit of using APC is offset with the increased risk for bleeding [142].…”

Section: Natural Anticoagulant Pathwaysmentioning

confidence: 99%

The hypercoagulable state in COVID-19: Incidence, pathophysiology, and management

Abou‐Ismail

Diamond

Kapoor

et al. 2020

Thrombosis Research

582

566

View full text Add to dashboard Cite

The 2019 coronavirus disease presents with a large variety of clinical manifestations ranging from asymptomatic carrier state to severe respiratory distress, multiple organ dysfunction and death. While it was initially considered primarily a respiratory illness, rapidly accumulating data suggests that COVID-19 results in a unique, profoundly prothrombotic milieu leading to both arterial and venous thrombosis. Consistently, elevated D-dimer level has emerged as an independent risk factor for poor outcomes, including death. Several other laboratory markers and blood counts have also been associated with poor prognosis, possibly due to their connection to thrombosis. At present, the pathophysiology underlying the hypercoagulable state is poorly understood. However, a growing body of data suggests that the initial events occur in the lung. A severe inflammatory response, originating in the alveoli, triggers a dysfunctional cascade of inflammatory thrombosis in the pulmonary vasculature, leading to a state of local coagulopathy. This is followed, in patients with more severe disease, by a generalized hypercoagulable state that results in macro-and microvascular thrombosis. Of concern, is the observation that anticoagulation may be inadequate in many circumstances, highlighting the need for alternative or additional therapies. Numerous ongoing studies investigating the pathophysiology of the COVID-19 associated coagulopathy may provide mechanistic insights that can direct appropriate interventional strategies.

show abstract

Section: Natural Anticoagulant Pathwaysmentioning

confidence: 99%

The hypercoagulable state in COVID-19: Incidence, pathophysiology, and management

Abou‐Ismail

Diamond

Kapoor

et al. 2020

Thrombosis Research

582

566

View full text Add to dashboard Cite

show abstract

“…The study showed that the seven-day DIC score was improved in the treatment group, but the 28-day mortality was not significantly different. In this study, a sample size of 114 patients was supposed to provide 90% power at a 5% two-sided α level for the mortality, and 105 patients for the seven-day DIC resolution [13]. In our study, according to Cohen [35], a sample size of 79 patients or 84 patients provided 80% power at a 5% two-sided α level for the mortality or the DIC resolution.…”

Section: Discussionmentioning

confidence: 99%

“…The Sepsis Coagulopathy Asahi Recombinant LE Thrombomodulin (SCARLET) randomized clinical trial, an expanded phase III clinical trial of the phase IIb study, also failed to show the improvement of thrombomodulin in the 28-day all-cause mortality in the treatment of sepsis-associated DIC [12]. On the contrary, recent retrospective observational studies in Japan claimed that ART-123 might be beneficial to treat sepsis-induced DIC in patients with severe coagulopathy [13] or severe respiratory failure [14].…”

Section: Introductionmentioning

confidence: 99%

Human Soluble Recombinant Thrombomodulin, ART-123, Resolved Early Phase Coagulopathies, but Did Not Significantly Alter the 28 Day Outcome in the Treatment of DIC Associated with Infectious Systemic Inflammatory Response Syndromes

Mori

Sera

et al. 2019

JCM

View full text Add to dashboard Cite

Disseminated intravascular coagulation (DIC) is a catastrophic systemic disorder of coagulation, resulting in uncontrollable bleeding, multiple organ failure, and death. Sepsis is one of the common causes of DIC. Despite many attempts to correct these coagulation pathologies, no adjunctive treatments have been shown to improve the mortality of DIC associated with sepsis. Although some clinical studies showed a recently developed human recombinant thrombomodulin, ART-123, might be effective in the treatment of DIC, few randomized, placebo-controlled studies have been conducted. In this study, we treated 60 DIC patients associated with systemic inflammatory response syndrome (SIRS) using ART-123 (n = 29) or saline as a placebo (n = 31). The basal clinical characteristics were similar in both groups. We compared clinical severity scores and DIC score in acute phase, and 28 day mortality between the two groups. Our study demonstrated the DIC score improved a few days earlier in the ART-123 group than the placebo group, and there were no major life-threatening adverse events in both groups. The overall survival rate at day 28 was not significantly altered. In conclusion, ART-123 can be used safely in DIC associated with infectious SIRS patients; however, its true efficacy in the treatment of DIC needs to be further investigated.

show abstract

“…Yamakawa et al found that in a small group of patients with sepsis-induced DIC administration of rhTM resulted in significant improvement in organ dysfunction as marked by Sequential Organ Failure Assessment (SOFA) scores and a significant reduction in 28day mortality versus controls [37]. A subsequent study by Kato et al focused on septic patients with mild versus severe coagulopathy and, once again, found an improvement in SOFA scores, especially the respiratory component, and 90day mortality amongst those in the severe group [38]. However, the SCARLET trial, which was a randomized controlled trial involving over 800 patients with sepsis-associated coagulopathy, failed to show a benefit in terms of 28-day mortality (Table 1) [39].…”

Section: Article Highlightsmentioning

confidence: 99%

Emerging therapeutic targets for sepsis

Tindal

Armstead

Monaghan

et al. 2021

Expert Opinion on Therapeutic Targets

View full text Add to dashboard Cite

Introduction: Sepsis is characterized by a dysregulated host response to infection. Sepsis-associated morbidity/mortality demands concerted research efforts toward therapeutic interventions which are reliable, broadly effective, and etiologically based. More intensive and extensive investigations on alterations in cellular signaling pathways, gene targeting as a means of modifying the characteristic hyper and/or hypo-immune responses, prevention through optimization of the microbiome, and the molecular pathways underlying the septic immune response could improve outcomes. ] Areas covered: The authors discuss key experimental mammalian models and clinical trials. They provide an evaluation of evolving therapeutics in sepsis and how they have built upon past and current treatments. Relevant literature was derived from a PubMed search spanning 1987-2020. Expert opinion: Given the complex nature of sepsis and the elicited immune response, it is not surprising that a single cure-all therapeutic intervention, which is capable of effectively and reliably improving patient outcomes has failed to emerge. Innovative approaches seek to address not only the disease process but modify underlying patient factors. A true improvement in sepsis-associated morbidity/mortality will require a combination of unique therapeutic modalities.

show abstract

Recombinant human soluble thrombomodulin improves mortality in patients with sepsis especially for severe coagulopathy: a retrospective study

Cited by 10 publications

References 32 publications

The hypercoagulable state in COVID-19: Incidence, pathophysiology, and management

The hypercoagulable state in COVID-19: Incidence, pathophysiology, and management

Human Soluble Recombinant Thrombomodulin, ART-123, Resolved Early Phase Coagulopathies, but Did Not Significantly Alter the 28 Day Outcome in the Treatment of DIC Associated with Infectious Systemic Inflammatory Response Syndromes

Emerging therapeutic targets for sepsis

Contact Info

Product

Resources

About