Published online 15 January 2010
(Haematologica 2010, 10.3324/haematol.2009.016121)
Copyright © 2010 by Ferrata Storti Foundation

This Article Full Text (PDF) Helley et al. Supplementary Appendix Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Helley, D. Search for Related Content PubMed PubMed Citation Articles by Helley, D. Related Collections Related Article

Article

Evaluation of hemostasis and endothelial function in patients with paroxysmal nocturnal hemoglobinuria receiving eculizumab

Dominique Helley^1,2,3, Régis Peffault de Latour^4,5,6, Raphaël Porcher^5,7, Celso Arrais Rodrigues⁴, Isabelle Galy-Fauroux^1,3, Jeanne Matheron², Arnaud Duval^3,8, Jean-François Schved⁹, Anne-Marie Fischer^1,2,3, Gérard Socié^4,5,6 on behalf of the French Society of Hematology

¹ Université Paris Descartes, Faculté de Médecine, Paris, France
² AP-HP, Service d’Hématologie biologique, Hôpital Européen Georges Pompidou, Paris, France
³ INSERM Unité 765, Faculté des Sciences Pharmaceutiques et Biologiques, Paris, France
⁴ AP-HP, Service d’Hématologie-Greffe, Hôpital Saint-Louis, Paris, France
⁵ Université Paris Diderot, Faculté de Médecine, Paris, France
⁶ INSERM U728, Hôpital Saint-Louis, Paris, France
⁷ INSERM U717, Hôpital Saint-Louis, Paris, France
⁸ AP-HP, Service de Médecine Interne, Hôpital Européen Georges Pompidou, Paris, France
⁹ Laboratoire Central d'Hématologie, CHU de Montpellier, Montpellier, France

Correspondence: Dominique Helley, Service d’Hématologie Biologique, Hôpital Européen Georges Pompidou, 20-40, Rue Leblanc, 75908 Paris cedex 15, France. E-mail: dominique.helley{at}egp.aphp.fr Phone: +33.1.56093905. Fax: +33.1.56093993

ABSTRACT

Background: Paroxysmal nocturnal hemoglobinuria (PNH) is associated with an increased risk of thrombosis, through unknown mechanisms.

Design and Methods: We studied 23 patients with PNH, before and after 5 and 11 weeks of treatment with eculizumab. We examined markers of thrombin generation and reactional fibrinolysis (prothrombin fragment 1+2 (F1+2), D-dimers, and plasmin-antiplasmin complexes (P-AP)), and endothelial dysfunction (tissue-plasminogen activator (t-PA), plasminogen activator inhibitor (PAI-1), soluble thrombomodulin (sTM), intercellular adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule (sVCAM-1), endothelial microparticles (EMPs)), and tissue factor pathway inhibitor (TFPI)).

Results: At baseline, vWF, sVCAM-1, the EMP count, and F1+2 and D-dimer levels were significantly elevated in the patients, including those with no history of clinical thrombosis. Treatment with eculizumab was associated with significant decreases in plasma markers of coagulation activation (F1+2, p=0.012, and D-dimers, p=0.01), and reactional fibrinolysis (P-AP, p=0.0002). Eculizumab treatment also significantly reduced plasma markers of endothelial cell activation (t-PA, p=0.0005, sVCAM-1, p<0.0001, and vWF, p=0.0047) and total (p=0.0008) and free (p=0.0013) TFPI plasma levels.

Conclusions: Our results suggest a new understanding of the contribution of endothelial cell activation to the pathogenesis of thrombosis in PNH. The terminal complement inhibitor, eculizumab, induced a significant and sustained decrease in the activation of both the plasma hemostatic system and the vascular endothelium, likely contributing to the protective effect of eculizumab on thrombosis in this setting.

Related Article

Paroxysmal nocturnal hemoglobinuria and eculizumab

Lucio Luzzatto, Antonio Maria Risitano, Rosario Notaro
Haematologica 2010 95: 523-526. [Full Text] [PDF]

This article has been cited by other articles:

				L. Luzzatto, A. M. Risitano, and R. Notaro Paroxysmal nocturnal hemoglobinuria and eculizumab Haematologica, April 1, 2010; 95(4): 523 - 526. [Full Text] [PDF]