The prognostic value of ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 repeats, member 13) deficiency in septic shock patients involves interleukin-6 and is not dependent on disseminated intravascular coagulation

Abstract

IntroductionADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 repeats, member 13) deficiency has been reported in patients with sepsis but its clinical relevance and pathophysiology remain unclear. Our objectives were to assess the clinical significance, prognostic value and pathophysiology of ADAMTS13 deficiency in patients with septic shock with and without disseminated intravascular coagulation (DIC).MethodsThis was a prospective monocenter cohort study of patients with septic shock. Von Willebrand Factor, ADAMTS13-related parameters and plasma IL-6 concentration were measured at inclusion to the study. Patients were categorized into three groups according to the presence of ADAMT13 deficiency (<30%) or DIC.ResultsThis study included 72 patients with a median age of 59 years (interquartile range (IQR) 50 to 71). Each of the included patients received vasopressors; 55 (76%) were under mechanical ventilation and 22 (33%) underwent renal replacement therapy. Overall, 19 patients (26%) had DIC, and 36 patients had ADMTS13 deficiency (50%). Patients with DIC, ADAMTS13 deficiency or both were more severe at ICU admission. Mortality was higher in septic shock patients from group one. By multivariate analysis, Simplified Acute Physiology Score 2 (SAPS2) score (odds ratio (OR) 1.11/point; 95% CI 1.01 to 1.24) and ADAMTS13 activity <30% (OR 11.86; 95% CI 1.36 to 103.52) were independently associated with hospital mortality. There was no correlation between ADAMTS13 activity and the International Society for Thrombosis and Haemostasis (ISTH) score (rs = -0.97, P = 0.41) suggesting that ADAMTS13 functional deficiency and DIC were independent parameters. IL-6 level was higher in patients with ADAMTS13 activity <30% [895 (IQR 330 to 1843) pg/mL versus 83 (IQR 43 to 118), P = 0.0003).ConclusionsSeptic shock was associated with a functional deficiency of ADAMTS13, independently of DIC. ADAMTS13 functional deficiency is then a prognostic factor for mortality in septic shock patients, independently of DIC.

Complement activation, inflammation and relative ADAMTS13 deficiency in secondary thrombotic microangiopathies

“…The standard therapy of secondary TMA is treatment of the coexisting disease, completed by plasma therapy (infusions of fresh frozen plasma, or plasma exchange). Since relative ADAMTS13 deficiency was demonstrated to predict poor prognosis in sepsis and in the systemic inflammatory response syndrome (Hyseni et al, 2014;Martin et al, 2007;Peigne et al, 2013), as well as this was also observed in our study, plasma supplementation appears to be a rational approach. As reported by Schwameis et al (2015) in a recent review, the potential mechanisms behind the insufficient cleavage capacity of ADAMTS13 during inflammation may include exhaustion, inhibition, proteolytic degradation of the enzyme, and competition.…”

Prognostic value of ADAMTS13 in patients with severe sepsis and septic shock

“…Clemens et al [26] also demonstrated that low ADAMTS13 levels were associated with a significantly higher DIC-score, but Peigne [21] observed no correlation between ADAMTS13 deficiency and DIC.…”

“…Peigne et al [21] emphasized the role of ADAMTS13 as a prognosis factor in septic shock and Ono et al [22] described decreased ADAMTS13 levels in 109 patients with sepsis-induced disseminated intravascular coagulation (DIC). Recently, a meta-analysis [23] revealed three studies that showed ADAMTS13 was significantly lower in sepsis than other critically ill non-septic patients [14,19,24].…”

What's new in the diagnosis and pathophysiology of thrombotic thrombocytopenic purpura

“…However, the incidence of severe ADAMTS13 deficiency in these conditions is uncertain. Some studies, covering hundreds of patients in total, report severe ADAMTS13 deficiency in ~9% of them, 36–38 whereas others report no instances of severe ADAMTS13 deficiency. 39,40 Differences in the study populations, possibly the prevalence of liver failure, may account for the different results.…”