Establishing prognostic markers associated with neutrophil extracellular traps and the activated contact system in thrombotic microangiopathy

Thrombotic microangiopathy (TMA) is a life-threatening thrombotic disorder. Neutrophil extracellular traps (NETs) and activation of the contact system are known to promote and propagate the formation of thrombus. Our study assessed the prognostic values of multiple NET markers and a contact system activation marker in patients with clinically suspected TMA. Patients (n = 138) with clinically suspected TMA were analyzed for the circulating levels of NET markers (neutrophil elastase, histone-DNA complexes, citrullinated histone H3 [Cit H3], and cell-free double-stranded DNA [dsDNA]); the contact system activation marker (activated factor XII [factor XIIa]); and other TMA-associated markers (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 [ADAMTS13] activity, von Willebrand factor antigen [vWF:Ag], von Willebrand factor ristocetin cofactor activity [vWF:Rco], and platelet counts). Low ADAMTS13 activity (hazard ratio [HR]: 4.85, P = 0.033), high vWF:Rco (HR: 9.46, P = 0.037), low platelet counts (HR: 7.45, P = 0.017), and high histone-DNA complexes (HR: 8.43, P = 0.015) were identified as independent markers of high mortality in multivariable Cox proportional hazards regression analysis. ADAMTS13, vWF:Rco, platelet counts, and histone-DNA complexes can be useful markers for identifying TMA patients at high risk of mortality.