Articles prepublished December 21, 2011

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

Journal:Thrombosis and Haemostasis
ISSN:0340-6245
DOI:http://dx.doi.org/10.1160/TH10-02-0138
Issue:2010: 104/5 (Nov) pp. 863-1082
Pages:1038-1043

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

S. Lovric (1), A. Lukasz (1), C. Hafer (1), J. T. Kielstein (1), M. Haubitz (1), H. Haller (1), P. Kümpers (1, 2)

(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

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.

Keywords

plasma exchange, Thrombotic microangiopathy, Angiopoietins, critically illness, anti-GBM disease

DOI

http://dx.doi.org/10.1160/TH10-02-0138

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