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Comparative Study
. 2006 Feb;10(1):R16.
doi: 10.1186/cc3966.

Upregulated but insufficient generation of activated protein C is associated with development of multiorgan failure in severe acute pancreatitis

Outi Lindstrom  1 , Leena Kylanpaa, Panu Mentula, Pauli Puolakkainen, Esko Kemppainen, Reijo Haapiainen, Jose A Fernandez, John H Griffin, Heikki Repo, Jari Petaja
Affiliations
Comparative Study

Upregulated but insufficient generation of activated protein C is associated with development of multiorgan failure in severe acute pancreatitis

Outi Lindstrom et al. Crit Care. 2006 Feb.

Abstract

Introduction: Disturbed protein C (PC) pathway homeostasis might contribute to the development of multiple organ failure (MOF) in acute pancreatitis (AP). We therefore evaluated circulating levels of PC and activated protein C (APC), evaluated monocyte deactivation in AP patients, and determined the relationship of these parameters to MOF.

Patients and methods: Thirty-one patients in the intensive care unit were categorized as cases (n = 13, severe AP with MOF) or controls (n = 18, severe AP without MOF). Blood samples were drawn every second day to determine the platelet count, the levels of APC, PC, and D-dimer, and the monocyte HLA-DR expression using flow cytometry. The APC/PC ratio was used to evaluate turnover of PC to APC.

Results: During the initial two weeks of hospitalization, low PC levels (<70% of the adult mean) occurred in 92% of cases and 44% of controls (P = 0.008). The minimum APC level was lower in cases than in controls (median 85% versus 97%, P = 0.009). Using 87% as the cut-off value, 8/13 (62%) cases and 3/18 (17%) controls showed reduced APC levels (P = 0.021). A total of 92% of cases and 50% of controls had APC/PC ratios exceeding the upper normal limit (P = 0.013). Plasma samples drawn before MOF showed low PC levels and high APC/PC ratios. HLA-DR-positive monocytes correlated with PC levels (r = 0.38, P < 0.001) and APC levels (r = 0.27, P < 0.001), indicating that the PC pathway was associated with systemic inflammation-triggered immune suppression.

Conclusion: PC deficiency and decreased APC generation in severe AP probably contributed to a compromised anticoagulant and anti-inflammatory defence. The PC pathway defects were associated with the development of MOF. The data support feasibility of testing the use of APC or PC to improve the clinical outcome in AP.

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Figures

Figure 1
Figure 1
Levels of (a) protein C (PC), (b) activated protein C (APC), and (c) APC/PC ratio during hospital stay in patients with acute pancreatitis. Control, patients with acute pancreatitis without multiple organ failure. The dotted lines indicate reference values for healthy individuals. Day 1 indicates the day of admission to the research hospital
Figure 2
Figure 2
The lowest (a) protein C (PC) and (b) activated protein PC (APC) values during the first two weeks of hospital care in acute pancreatitis patients with multiple organ failure (cases) and in those without organ failure (controls). P = 0.055 and P = 0.022 for PC and APC, respectively; Mann-Whitney U test.
Figure 3
Figure 3
Follow-up concentrations of (a) protein C (PC), (b) activated protein C (APC), and (c) APC/PC ratio during the stay in hospital in nine patients with organ failure. There was no significant influence of time of sampling on any parameter (Friedman's test P > 0.05).
Figure 4
Figure 4
Correlations between percentage of HLA-DR-positive monocytes and (a) protein C (PC), (b) activated PC (APC), (c) platelet count, and (d) D-dimer concentrations. Correlation coefficients are presented for combined data of organ failure and control patients. E9, × 109.
See this image and copyright information in PMC

Comment in

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