Increased activation of protein C, but lower plasma levels of free, activated protein C in uraemic patients: relationship with systemic inflammation and haemostatic activation

Autor:	D, Mezzano, F, España, O, Panes, P, Medina, E, Pais, G, Marshall, R, Tagle, P, Downey, S, Caceres, F, González, T, Quiroga, J, Pereira
Rok vydání:	2001
Předmět:	Adult Male Tumor Necrosis Factor-alpha Interleukin-8 Thrombin Fibrinogen Middle Aged Antithrombins Statistics Nonparametric Fibrin Fibrinogen Degradation Products C-Reactive Protein alpha 1-Antitrypsin von Willebrand Factor Humans Kidney Failure Chronic Female Fibrinolysin Aged Protein C
Zdroj:	British journal of haematology. 113(4)
ISSN:	0007-1048
Popis:	Chronic renal failure (CRF) courses with both systemic inflammatory reaction and haemostatic activation. We explored the relationship of these processes with plasma levels of free, activated protein C (APC) and complexes of APC with its inhibitors in patients with CRF under conservative treatment. Plasma concentrations of inflammatory cytokines [tumour necrosis factor alpha (TNFalpha) and interleukin 8], acute-phase proteins (C-reactive protein, fibrinogen, alpha1-anti-trypsin and von Willebrand factor), and markers of haemostatic activation (thrombin-anti-thrombin complexes, plasmin-anti-plasmin complexes, and fibrin and fibrinogen degradation products) were higher in patients than in controls. Inflammatory and haemostatic markers were significantly and positively correlated. Total plasma APC and APC:alpha1-anti-trypsin (alpha1AT) complexes were 44% and 75% higher in patients than in controls (P = 0.0001), whereas free APC was 20% lower (P0.015). No significant difference was observed in APC:protein C inhibitor (PCI) complexes between both groups. The free/total APC ratio was significantly lower in patients than in controls (P0.0001). Total plasma APC and APC:alpha1AT were positively correlated with activation markers of haemostasis and acute-phase proteins, whereas free APC was inversely correlated with plasma levels of creatinine, acute-phase proteins and fibrin degradation products (FnDP). Systemic inflammation and activation of haemostasis are interrelated processes in CRF. APC generation was increased in response to elevated thrombin production, but the inflammatory reaction, associated with increased synthesis of alpha1AT, reduced its anticoagulant effect. Lower free plasma APC in CRF may be pathogenically associated with atherothrombosis, a major cause of death in this disease.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=pmid________::891c02244d7761f9e8d69de7cfdb7b62 https://pubmed.ncbi.nlm.nih.gov/11442482 Zobrazit plný text záznamu Plný text