The pathogenesis and prognosis of immune thrombotic thrombocytopenic purpura (iTTP) may be effectively predicted by markers including plasma levels of S100A8/A9, histone/DNA complexes, and cell-free DNA, according to research published in the Journal of Thrombosis and Haemostasis.

A rare and potentially life-threatening thrombotic disorder, iTTP is characterized by severe deficiency in ADAMTS13 activity, the cause of which may be autoantibodies directed against ADAMTS13. Although previous research suggested that iTTP may be caused by acute inflammation and neutrophil activation, leading to the release of neutrophil azurophilic granular contents including S100A8/A9, neutrophil extracellular traps, and cell-free DNA, whether these markers are related to disease outcomes is unclear.

For this study, researchers attempted to determine “the association of plasma S100A8/A9, [cell-free] DNA, and histone/DNA complexes with the severity and outcome of patients with acute iTTP after standard of care consisting of therapeutic plasma exchange, corticosteroids, and rituximab.”

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Overall, 108 acute iTTP episodes in 94 unique patients were evaluated and compared with data from a control group of individuals without iTTP. Over the 108 episodes, 11 deaths were recorded. Among those patients who survived or died during an iTTP episode, the median ages were 45 and 54 years, 47 (56%) and 6 (60%) were women, and 68 (81%) and 7 (70%) were Black, respectively.

Of evaluated demographic and comorbidity data, hypertension and diabetes status were not significantly different between the 2 groups, although Glasgow Coma Scale score did differ (median score, 15 in the survivor group vs 10 among those who died; P <.001).

Patients with acute iTTP had higher plasma levels of S100A8/A9 (median, 84.8 μg/mL), histone/DNA complexes (median, 55.7 U/mL), and cell-free DNA (median, 937.7 ng/mL) than the control group. Citrullinated histone H3 levels (median, 3.8 ng/mL) were also higher in the group with acute iTTP.

Higher levels of S100A8/A9 (hazard ratio [HR], 11.5; P =.021), histone/DNA complex (HR, 10.3; P =.001), and cell-free DNA (HR, 12.8; P =.014) were each linked with a greater likelihood of organ damage and death.

Disclosures: Some authors have declared affiliations with or received funding from the pharmaceutical industry. Please refer to the original study for a full list of disclosures.


Sui J, Lu R, Halkidis K, et al. Plasma levels of S100A8/A9, histone/DNA complexes, and cell-free DNA predict adverse outcomes of immune thrombotic thrombocytopenic purpura. J Thromb Haemost. Published online November 14, 2020. doi:10.1111/jth.15176