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
1  Department of Hematology, BMT Unit, G. Papanikolaou Hospital, Thessaloniki, Greece
,
Akrivi Chrysanthopoulou
2  Laboratory of Molecular Hematology, Democritus University of Thrace, Alexandroupolis, Greece
,
Ioanna Sakellari
1  Department of Hematology, BMT Unit, G. Papanikolaou Hospital, Thessaloniki, Greece
,
Ioannis Batsis
1  Department of Hematology, BMT Unit, G. Papanikolaou Hospital, Thessaloniki, Greece
,
Despina Mallouri
1  Department of Hematology, BMT Unit, G. Papanikolaou Hospital, Thessaloniki, Greece
,
Tasoula Touloumenidou
1  Department of Hematology, BMT Unit, G. Papanikolaou Hospital, Thessaloniki, Greece
,
Apostolia Papalexandri
1  Department of Hematology, BMT Unit, G. Papanikolaou Hospital, Thessaloniki, Greece
,
Alexandros Mitsios
2  Laboratory of Molecular Hematology, Democritus University of Thrace, Alexandroupolis, Greece
,
Athanasios Arampatzioglou
2  Laboratory of Molecular Hematology, Democritus University of Thrace, Alexandroupolis, Greece
,
Konstantinos Ritis
2  Laboratory of Molecular Hematology, Democritus University of Thrace, Alexandroupolis, Greece
,
Robert Alan Brodsky
3  Division of Hematology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States
,
Ioannis Mitroulis*
2  Laboratory of Molecular Hematology, Democritus University of Thrace, Alexandroupolis, Greece
4  Institute for Clinical Chemistry and Laboratory Medicine, Technische Universität Dresden, Dresden, Germany
5  National 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*
1  Department of Hematology, BMT Unit, G. Papanikolaou Hospital, Thessaloniki, Greece
› Author Affiliations
Funding E.G. was supported by the European Hematology Association Clinical Research Grant 2016. I.M. and A.C. were supported by BMBF/GSRT German-Greek Bilateral Research and Innovation Program, “BRIDGING,” grant no. T2DGED-0101. I.M. was supported by the National Center for Tumor Diseases, Dresden, Germany.
Further Information

Publication History

05 January 2019

14 May 2019

Publication Date:
02 July 2019 (eFirst)

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.

Authors' Contributions

E.G., K.R., R.A.B., I.M., and A.c.A were responsible for the study conception and design. E.G., I.S., I.B., and D.M. recruited study participants and collected clinical data. A.C., A.A., T.T., A.P., A.M., and A.l.A performed experiments and acquired data. E.G. and I.M. analyzed and interpreted the data. E.G., A.C., K.R., R.A.B., I.M., and A.c.A drafted the manuscript and performed critical revisions. All authors approved the final version of the manuscript.


* These authors share equal contribution.


Supplementary Material