Circulating DNA and myeloperoxidase indicate disease activity in patients with thrombotic microangiopathies

Fuchs, Tobias A; Kremer Hovinga, Johanna A; Schatzberg, Daphne; Wagner, Denisa D; Lämmle, Bernhard (2012). Circulating DNA and myeloperoxidase indicate disease activity in patients with thrombotic microangiopathies. Blood, 120(6), pp. 1157-64. Washington, D.C.: American Society of Hematology 10.1182/blood-2012-02-412197

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Thrombotic microangiopathies (TMAs) are a group of life-threatening disorders characterized by thrombocytopenia, fragmentation of erythrocytes, and ischemic organ damage. Genetic disorders, autoimmune disease, and cancer are risk factors for TMAs, but an additional, unknown trigger is needed to bring about acute disease. Recent studies suggest that DNA and histones are released during inflammation or infection and stimulate coagulation, thrombosis, thrombocytopenia, and organ damage in mice. We show that extracellular DNA and histones as well as markers of neutrophils are present in acute TMAs. Analysis of plasma from TMA patients of different clinical categories revealed elevated levels of DNA-histone complexes and myeloperoxidase (MPO) from neutrophil granules as well as S100A8/A9, a heterocomplex abundant in neutrophil cytosol. During therapy of thrombotic thrombocytopenic purpura, a subtype of TMAs often associated with severe ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin type 1 motifs, member 13) deficiency, plasma DNA and MPO were inversely correlated with platelet counts, and their levels indicated amelioration or exacerbation of the disease. ADAMTS13 deficiency together with increased levels of plasma DNA and MPO were characteristic for acute thrombotic thrombocytopenic purpura. A minor infection often precedes acute TMA and extracellular DNA and histones released during the inflammatory response could provide the second hit, which precipitates acute TMA in patients with pre-existing risk factors.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Haematology and Central Haematological Laboratory

UniBE Contributor:

Kremer Hovinga, Johanna Anna and Lämmle, Bernhard

ISSN:

0006-4971

Publisher:

American Society of Hematology

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:28

Last Modified:

06 Dec 2013 13:32

Publisher DOI:

10.1182/blood-2012-02-412197

PubMed ID:

22611154

Web of Science ID:

000307449300005

URI:

https://boris.unibe.ch/id/eprint/10374 (FactScience: 216246)

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