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


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.


CONCLUSIONS
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.
Lindstrom
Outi
O
Second Department of Surgery, Helsinki University Central Hospital and University of Helsinki, Finland.
Kylanpaa
Leena
L
Mentula
Panu
P
Puolakkainen
Pauli
P
Kemppainen
Esko
E
Haapiainen
Reijo
R
Fernandez
Jose A
JA
Griffin
John H
JH
Repo
Heikki
H
Petaja
Jari
J
D000208:Acute Disease; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D007362:Intensive Care Units; D008297:Male; D008875:Middle Aged; D009102:Multiple Organ Failure / Q000097:blood* / Q000209:etiology; D010195:Pancreatitis / Q000097:blood* / Q000150:complications; D011486:Protein C / Q000096:biosynthesis* / Q000378:metabolism* / Q000502:physiology; D012720:Severity of Illness Index; D015398:Signal Transduction / Q000502:physiology; D015854:Up-Regulation / Q000502:physiology*
D011486:Protein C