Assessment of ADAMTS-13 Level in Hospitalized Children with Serious Bacterial Infections as a Possible Prognostic Marker

Abstract

Background and objectives: In children, acute infection is the most common cause of visits in the primary care or emergency department. In 2002, criteria for diagnostics of pediatric sepsis were published, and then revised in 2016 as “life-threatening organ dysfunction due to a dysregulated host response to infection”. In the pathophysiology of sepsis endothelial dysfunction plays a very important role. Deficient proteolysis of von Willebrand factor, due to reduced ADAMTS-13 activity, results in disseminated platelet-rich thrombi in the microcirculation. ADAMTS-13 deficiency has been detected in systemic inflammation. The clinical relevance of ADAMTS-13 during sepsis is still unclear. We aimed to investigate the possible use of ADAMTS-13 as a prognostic marker in children with serious bacterial infection (SBI). Materials and Methods: Inclusion criteria were hospitalized children with SBI, aged from 1 month to 17 years. SBI was defined based on available clinical, imaging, and later also on microbiological data. Sepsis was diagnosed using criteria by The International Consensus Conference. In all the patients, the levels of ADAMTS-13 were measured at the time of inclusion. Results: Data from 71 patients were analyzed. A total of 47.9% (34) had sepsis, 21.1% (15) were admitted to the ICU, 8.5% (6) had mechanical ventilator support, and 4.2% (3) patients had a positive blood culture. The median level of ADAMTS-13 in this study population was 689.43 ng/mL. Patients with sepsis, patients admitted to the Intensive Care Unit, and patients in need of mechanical ventilator support had significantly lower levels of ADAMTS-13. None of the patients had ADAMTS-13 deficiency. In patients with SBI, the area under the curve (AUC) to predict sepsis was 0.67. A cut-off ADAMTS-13 level of ≤730.49 had 82% sensitivity and 60% specificity for sepsis in patients with SBI. Conclusions: ADATMS-13 levels were lower in patients with SBI and sepsis, but AUC and sensitivity were too low to accept it as a prognostic marker.

A Global Assessment of Coagulation Profile and a Novel Insight into Adamts-13 Implication in Neonatal Sepsis

“…Decreased ADAMTS-13 levels have been previously described in several studies regarding adult and pediatric patients with sepsis [37,[40][41][42][43][44][45][46][47][48][49][50][51]. ADAMTS-13 levels in sepsis have been measured at around 20-43% of normal levels and an imbalance in the VWF/ADAMTS-13 system is observed under inflammatory conditions [33,42].…”

Immunothrombosis: Molecular Aspects and New Therapeutic Perspectives

“…Additionally, pathogen and cytokines activate the endothelium, producing a prothombotic state promoting multimeric chains of UL-VWF release to endothelial cell surface where they will bind platelets [ 45 ]. Usually, UL-VWF is broken by ADAMTs13 into small multimers, however, in patients with sepsis, ADAMTs13 is reduced, being unable to break these long structures which originate in a string surrounded by platelets and neutrophils that are the bases for microthrombi formation [ 46 ]. Finally, during sepsis, several anticoagulant proteins are reduced, such as protein C, protein S, and antithrombin, favoring thrombin generation and fibrin formation [ 47 ].…”