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Plasma levels of S100A8/A9, histone/DNA complexes, and cell‐free DNA predict adverse outcomes of immune thrombotic thrombocytopenic purpura
Author(s) -
Sui Jingrui,
Lu Ruinan,
Halkidis Konstantine,
Kocher Nicole K.,
Cao Wenjing,
Marques Marisa B.,
Zheng X. Long
Publication year - 2021
Publication title -
journal of thrombosis and haemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.947
H-Index - 178
eISSN - 1538-7836
pISSN - 1538-7933
DOI - 10.1111/jth.15176
Subject(s) - medicine , hazard ratio , thrombotic thrombocytopenic purpura , gastroenterology , interquartile range , immunology , histone , adamts13 , confidence interval , platelet , dna , biology , genetics
Background Immune thrombotic thrombocytopenic purpura (iTTP) is a life‐threatening blood disorder, primarily resulting from autoantibodies against ADAMTS13. Infection or inflammation often precedes acute iTTP. However, the association of inflammation and inflammatory mediators with disease severity and outcome of acute iTTP is not fully assessed. Objectives Here, we determined plasma levels of S100A8/A9, histone/DNA complexes, citrullinated histone H3 (CitH3), and cell‐free DNA (cfDNA) in a cohort of 108 acute episodes from 94 unique iTTP patients and healthy controls, and assessed the association of each of these biomarkers with the disease severity and mortality. Results All acute iTTP patients had significantly increased plasma levels of S100A8/A9 (median 84.8, interquartile range [IQR] 31.2‐157.4 µg/mL), histone/DNA complexes (median 55.7, IQR 35.8‐130.8 U/mL), CitH3 (median 3.8, IQR 2.2‐6.4 ng/mL), and cfDNA (median 937.7, IQR 781.3‐1420.0 ng/mL) on the admission blood samples when compared with healthy controls. An increased plasma level of S100A8/A9, histone/DNA complex and cfDNA was associated with organ damage, coagulopathy, and mortality in iTTP. After being adjusted for age and history of hypertension, Cox proportional hazard regression analysis demonstrated that a hazard ratio (95% confidence interval) for an elevated plasma level of S100A8/A9, histone/DNA complexes, and cfDNA was 11.5 (1.4‐90.9) ( P = .021), 10.3 (2.7‐38.5) ( P = .001), and 12.8 (3.9‐42.0) ( P = .014), respectively. Conclusion These results indicate that inflammation or plasma inflammatory mediators such as S100A8/A9 or NETosis markers such as histone/DNA complexes and cfDNA may play a role in pathogenesis of iTTP, which may help stratify patients with a high risk of death during acute iTTP episodes.