Thromb Haemost 2010; 104(05): 1038-1043
DOI: 10.1160/TH10-02-0138
Endothelium and Vascular Development
Schattauer GmbH

Removal of elevated circulating angiopoietin-2 by plasma exchange – A pilot study in critically ill patients with thrombotic microangiopathy and anti-glomerular basement membrane disease

Svjetlana Lovric*
1  Department of Nephrology & Hypertension, Hannover Medical School, Hannover, Germany
,
Alexander Lukasz*
1  Department of Nephrology & Hypertension, Hannover Medical School, Hannover, Germany
,
Carsten Hafer
1  Department of Nephrology & Hypertension, Hannover Medical School, Hannover, Germany
,
Jan T. Kielstein
1  Department of Nephrology & Hypertension, Hannover Medical School, Hannover, Germany
,
Marion Haubitz
1  Department of Nephrology & Hypertension, Hannover Medical School, Hannover, Germany
,
Hermann Haller
1  Department of Nephrology & Hypertension, Hannover Medical School, Hannover, Germany
,
Philipp Kümpers
1  Department of Nephrology & Hypertension, Hannover Medical School, Hannover, Germany
2  Department of Medicine D, Division of General Internal Medicine, Nephrology, and Rheumatology, University Hospital Münster, Münster, Germany
› Author Affiliations
Further Information

Publication History

Received: 22 February 2010

Accepted after major revision: 15 July 2010

Publication Date:
24 November 2017 (online)

Summary

In critically ill patients, the massive release of angiopoietin-2 (Ang-2) from Weibel-Palade bodies interferes with protective angiopoietin-1 (Ang-1)/Tie2 signalling in endothelial cells, thus leading to vascular inflammation and subsequent organ-dysfunction. We hypothesised that plasma exchange (PE) is efficient for lowering excess Ang-2 levels in critically ill patients with thrombocytic microangiopathy (TMA) or anti-glomerular basement membrane (anti-GBM) disease. Plasma Ang-1 and Ang-2 were measured by immuno-luminometric assays in patients with TMA (n=9) or anti-GBM disease (n=4) before and after up to four PE sessions. Twenty apparently healthy volunteers served as controls. Median (IQR) plasma levels of Ang-2 were markedly increased in patients with TMA (7.3 (2.4–21.1) ng/ml) and anti-GBM disease (5.8 (3.4–7.0) ng/ml) compared to healthy controls (1.0 (0.9–1.4) ng/ml, p <0.001). Moreover, Ang-1 plasma levels were decreased in both, TMA (1.02 (0.62–1.62) ng/ml) and anti-GBM disease patients (0.74 (0.59–3.62) ng/ml) compared to healthy controls (2.5 (1.93–3.47) ng/ ml, p <0.005). During a total of 32 treatments, PE effectively lowered elevated mean (SD) Ang-2 plasma levels by 36.7 ± 19.6 % per treatment (p <0.0001), whereas low Ang-1 plasma levels remained unchanged (0.3 ± 58.5 %; p =0.147). Ang-2 levels declined to almost normal values during ≤4 PE treatments (Friedman´s test p <0.0001). PE is an effective method to remove excess circulating Ang-2. It remains to be elucidated if the removal of Ang-2 is crucial to ameliorate endothelial damage in critically ill patients with severely altered endothelial integrity.

* SL and AL contributed equally to the manuscript and are joint first authors.