Thromb Haemost 1991; 66(04): 420-425
DOI: 10.1055/s-0038-1646431
Review Article
Schattauer GmbH Stuttgart

Low Levels of the Anticoagulant Activity of Protein C in Patients with Chronic Renal Insufficiency: an Inhibitor of Protein C Is Present in Uremic Plasma

Elena M Faioni
The A. Bianchi Bonomi Hemophilia and Thrombosis Center and the Institute of Internal Medicine, IRCCS Maggiore Hospital and University of Milan, Bergamo, Italy
,
Franca Franchi
The A. Bianchi Bonomi Hemophilia and Thrombosis Center and the Institute of Internal Medicine, IRCCS Maggiore Hospital and University of Milan, Bergamo, Italy
,
Alessandro Krachmalnicoff
The A. Bianchi Bonomi Hemophilia and Thrombosis Center and the Institute of Internal Medicine, IRCCS Maggiore Hospital and University of Milan, Bergamo, Italy
,
Carla Valsecchi
The A. Bianchi Bonomi Hemophilia and Thrombosis Center and the Institute of Internal Medicine, IRCCS Maggiore Hospital and University of Milan, Bergamo, Italy
,
Gian Luigi Viganò
*  Mario Negri Institute for Pharmacological Research, Bergamo, Italy
,
Giuseppe Remuzzi
*  Mario Negri Institute for Pharmacological Research, Bergamo, Italy
,
Pier Mannuccio Mannucci
The A. Bianchi Bonomi Hemophilia and Thrombosis Center and the Institute of Internal Medicine, IRCCS Maggiore Hospital and University of Milan, Bergamo, Italy
› Author Affiliations
Further Information

Publication History

Received 28 November 1990

Accepted 03 April 1991

Publication Date:
25 July 2018 (online)

Summary

Twenty-nine of 54 uremic patients had low levels of protein C measured as anticoagulant activity, contrasting with normal levels measured as amidolytic activity or antigenic concentration. We demonstrate that this discrepancy is due to the presence of a soluble plasma inhibitor that interferes specifically with the anticoagulant activity of activated protein C. The inhibitor does not interfere with other coagulation assays. It is resistent to diisopropylfluorophosphate, high temperatures and repeated freezing and thawing. It can be dissociated from protein C by anti-protein C antibodies or by dialysis in vitro and in vivo. It binds to positively charged resins and can be eluted with high salt concentrations without losing its inhibitory capacity. The inhibitory effect is correlated with plasma creatinine levels and fluctuates with time.