DOI: 10.1097/01.mpa.0000193717.68728.ff
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Issn Print: 0885-3177
Publication Date: 2005/11/01
UP-REGULATED BUT INSUFFICIENT GENERATION OF ACTIVATED PROTEIN C IS ASSOCIATED WITH DEVELOPMENT OF MULTI-ORGAN FAILURE IN SEVERE ACUTE PANCREATITIS
P Mentula; O Lindstrom; L Kylanpaa; E Kemppainen; P Puolakkainen; R Haapiainen; J A Fernandez; J H Griffin; H Repo; J Petaja
+ Author Information
Author Information: Second Department of Surgery, Helsinki University Central Hospital and University of Helsinki, Helsinki, Finland;
Excerpt
Disturbed protein C homeostasis might contribute to multi-organ failure (MOF) in severe acute pancreatitis (AP). We evaluated the changes in activated protein C (APC) and protein C (PC) and their correlation with routine coagulation parameters and degree of monocyte immunoactivation in 31 patients with AP treated in intensive care unit (ICU). Patients were divided into cases (13 severe AP patients with MOF) and controls (15 patients with severe AP without MOF and 3 patients with mild AP). Concentrations of APC and PC were measured every second day. Monocyte immunoactivation was evaluated by monocyte HLA-DR density. D-dimer was determined according to hospital routine. During the first two weeks of hospitalization, low protein C (<70% of adult mean) was observed in 92 % of cases and 44 % of controls (P = 0.008). APC was within the normal range in all samples but the minimum observed APC level was lower in cases than in controls (median 84.9% vs. 96.5%, P = 0.009). Using 87 % as cut-off for APC, 62% of cases and 17% of controls showed APC levels below this limit (P = 0.021). 92% of cases and 50% of controls had APC/PC ratios exceeding the upper normal limit (P = 0.0129). There were significant correlations between HLA-DR density and PC (R = 0.38, P < 0.001) and APC (R = 0.27, P < 0.001), but no correlation between D-dimer and PC. We conclude that severe AP may be associated with compromised ability to enhance anticoagulant and anti-inflammatory defense by APC upon coagulopathy induced demand and PC deficiency may predispose the patients to development of MOF. Association of PC pathway with inflammatory regulation in severe AP was demonstrated.
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