Deficiency of ADAMTS-13 in pediatric patients with severe sepsis and impact on in-hospital mortality

Abstract

BackgroundThe enzyme involved in regulating the size of vWF (von Willebrand factor) in plasma is ADAMTS-13 (A disintegrin and metalloprotease with thrombospondin type-1 motives). Deficient proteolysis of ULvWF (ultra large von Willebrand factor) due to reduced ADAMTS-13 activity results in disseminated platelet-rich thrombi in the microcirculation characteristic of thrombotic thrombocytopenic purpura. Reduced ADAMTS-13 has also been observed in severe sepsis and is associated with poor survival. We conducted this study to detect ADAMTS-13 deficiency and its impact on in-hospital mortality in pediatric patients with severe sepsis.MethodsPediatric patients diagnosed with severe sepsis were recruited for the study. Baseline clinical characteristics were noted. ADAMTS-13 antigen levels were assayed by ELISA. According to ADAMTS-13 levels, patients were grouped as deficient and non-deficient. Comparison was done with regard to some clinical and biological characteristics and in-hospital mortality between the two groups.ResultsA total of 80 patients were enrolled in the study. The median age of the patients was 3.1 years (Range: 0.1-15 years). ADAMTS-13 deficiency with levels less than 350 ng/dl was found in 65% patients. In patients with ADAMTS-13 deficiency, 75.6% had low platelets of less than 150 × 109/L. In-hospital mortality was 42.3% and 35.7% in ADAMTS-13 deficient and non-deficient group, respectively.ConclusionMajority of the pediatric patients admitted to hospital with severe sepsis exhibit ADAMTS-13 deficiency. ADAMTS-13 deficiency might play a role in sepsis-induced thrombocytopenia. More studies are needed to evaluate the role of ADAMTS-13 deficiency on in-hospital mortality.

The role of ADAMTS‐13 in the coagulopathy of sepsis

“…As ADAMTS‐13 levels in this study were measured with a urea‐based assay, these much reduced levels may have been spuriously low . Studies in septic children have also reported decreased ADAMTS‐13 levels in the majority of cases, with the deficiency strongly correlating with more severe coagulopathy . Low levels of ADAMTS‐13 in sepsis are associated with reduced levels of cleaved VWF .…”

“…Significantly lower ADAMTS‐13 levels are seen at the time of intensive care admission in eventual non‐survivors . Patients with ADAMTS‐13 plasma levels of ≤50% had an approximately 10% higher risk of death than patients who presented with no or only mild reductions in ADAMTS‐13 levels . One recent study demonstrated an approximately 50% lower survival rate in patients (mortality of 59%) with septic shock and ADAMTS‐13 levels of < 30% than in patients with higher levels of ADAMTS‐13 (mortality of 28%) .…”

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

“…Previous studies have shown a significant association between thrombocytopenia and low ADAMTS13 with mortality [19,33].…”

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

“…Similarly, reduced or severely deficient ADAMTS13 activity was found in adult (Merayo-Chalico et al, 2014;Jiang et al, 2014;Mannucci et al, 2003b) and in pediatric (Muscal et al, 2011) patients with systemic lupus erythematosus and systemic sclerosis. In addition, a decrease in ADAMTS13 activity was described in secondary TMA in response to inflammatory (Claus et al, 2009;Bockmeyer et al, 2008), infective (Karim et al, 2013), or extracorporeal stimuli including solid organ transplantation (Verbiest et al, 2014;Mannucci et al, 2005). Decreased ADAMTS13 activity relative to increased von Willebrand factor (VWF) levels, appears to be a universal, clinically useful biomarker of such processes (Schwameis et al, 2015).…”