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Increased activation of protein C, but lower plasma levels of free, activated protein C in uraemic patients: relationship with systemic inflammation and haemostatic activation
Author(s) -
Mezzano Diego,
España Francisco,
Panes Olga,
Medina Piedad,
Pais Edgar,
Marshall Guillermo,
Tagle Rodrigo,
Downey Patricio,
Caceres Soledad,
González Fernando,
Quiroga Teresa,
Pereira Jaime
Publication year - 2001
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1046/j.1365-2141.2001.02848.x
Subject(s) - protein c , acute phase protein , plasmin , fibrinogen , thrombin , medicine , fibrin , c reactive protein , endocrinology , chemistry , inflammation , protein s , blood proteins , immunology , platelet , biochemistry , enzyme
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 (TNFα) and interleukin 8], acute‐phase proteins (C‐reactive protein, fibrinogen, α 1 ‐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:α 1 ‐anti‐trypsin (α 1 AT) complexes were 44% and 75% higher in patients than in controls ( P = 0·0001), whereas free APC was 20% lower ( P < 0·015). 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 ( P < 0·0001). Total plasma APC and APC:α 1 AT 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 α 1 AT, reduced its anticoagulant effect. Lower free plasma APC in CRF may be pathogenically associated with atherothrombosis, a major cause of death in this disease.