Linking Complement Activation, Coagulation, and Neutrophils in Transplant-Associated Thrombotic Microangiopathy

Eleni Gavriilaki; Akrivi Chrysanthopoulou; Ioanna Sakellari; Ioannis Batsis; Despina Mallouri; Tasoula Touloumenidou; Apostolia Papalexandri; Alexandros Mitsios; Athanasios Arampatzioglou; Konstantinos Ritis; Robert Alan Brodsky; Ioannis Mitroulis; Achilles Anagnostopoulos

doi:10.1055/s-0039-1692721

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2019; 119(09): 1433-1440
DOI: 10.1055/s-0039-1692721

Coagulation and Fibrinolysis

Georg Thieme Verlag KG Stuttgart · New York

Linking Complement Activation, Coagulation, and Neutrophils in Transplant-Associated Thrombotic Microangiopathy

Eleni Gavriilaki

¹Department of Hematology, BMT Unit, G. Papanikolaou Hospital, Thessaloniki, Greece

,

Akrivi Chrysanthopoulou

²Laboratory of Molecular Hematology, Democritus University of Thrace, Alexandroupolis, Greece

,

Ioanna Sakellari

¹Department of Hematology, BMT Unit, G. Papanikolaou Hospital, Thessaloniki, Greece

,

Ioannis Batsis

¹Department of Hematology, BMT Unit, G. Papanikolaou Hospital, Thessaloniki, Greece

,

Despina Mallouri

¹Department of Hematology, BMT Unit, G. Papanikolaou Hospital, Thessaloniki, Greece

,

Tasoula Touloumenidou

¹Department of Hematology, BMT Unit, G. Papanikolaou Hospital, Thessaloniki, Greece

,

Apostolia Papalexandri

¹Department of Hematology, BMT Unit, G. Papanikolaou Hospital, Thessaloniki, Greece

,

Alexandros Mitsios

²Laboratory of Molecular Hematology, Democritus University of Thrace, Alexandroupolis, Greece

,

Athanasios Arampatzioglou

²Laboratory of Molecular Hematology, Democritus University of Thrace, Alexandroupolis, Greece

,

Konstantinos Ritis

²Laboratory of Molecular Hematology, Democritus University of Thrace, Alexandroupolis, Greece

,

Robert Alan Brodsky

³Division of Hematology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States

,

Ioannis Mitroulis^*

²Laboratory of Molecular Hematology, Democritus University of Thrace, Alexandroupolis, Greece

⁴Institute for Clinical Chemistry and Laboratory Medicine, Technische Universität Dresden, Dresden, Germany

⁵National Center for Tumor Diseases, Partner Site Dresden, of the German Cancer Research Center, Heidelberg and of the Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, and of the Helmholtz Association/Helmholtz-Zentrum Dresden-Rossendorf, Dresden, Germany

,

Achilles Anagnostopoulos^*

¹Department of Hematology, BMT Unit, G. Papanikolaou Hospital, Thessaloniki, Greece

› Author Affiliations

Abstract

Transplant-associated thrombotic microangiopathy (TA-TMA) is a severe and life-threatening complication of hematopoietic cell transplantation (HCT) that often coincides with graft-versus-host-disease (GVHD). Although endothelial damage seems to be the common denominator for both disorders, the role of complement system, neutrophils, and coagulation has not been clarified. In an effort to distinguish the pathogenesis of TA-TMA from GVHD, we evaluated markers of complement activation, neutrophil extracellular trap (NET) release, endothelial damage, and activation of coagulation cascade in the circulation of patients with these two disorders, as well as control HCT recipients without TA-TMA or GVHD. We observed that the terminal complement product C5b-9 levels, the levels of markers of NET formation, and thrombin–antithrombin complex levels were significantly increased in the TA-TMA group compared with patients without complications, whereas there was no significant difference between the GVHD and the control group. On the other hand, the levels of circulating thrombomodulin, an endothelial damage marker, were significantly increased in both TA-TMA and GVHD patients. These findings propose a role for the interplay between complement system, neutrophil activation through NET release, and activation of the coagulation cascade in TA-TMA.

Keywords

thrombotic microangiopathy - hematopoietic cell transplantation - graft-versus-host disease - complement - neutrophil extracellular traps

Full Text

References

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Supplementary Material

Supplementary Material