Decreased protein C function predicts mortality in patients with cirrhosis.

Abstract

INTRODUCTION:

Protein C (PrC), a physiological anticoagulant, regulates inflammation and cell death and has known predictive/therapeutic roles in sepsis. Accumulating evidences suggest plasma hypercoagulability results in progression of fibrosis and formation of microclots causing end-organ dysfunction. We investigated a possible association between natural anticoagulants-PrC, protein S (PrS) and antithrombin III (AT)-and clinical outcomes in cirrhotics.

METHODS:

Functional PrC, PrS and AT were analysed in 515 cirrhotic patients and compared with 229 noncirrhotics. Among those with cirrhosis, we conducted multivariable predictive model on 3-month survival to assess the prognostic ability of anticoagulants.

RESULTS:

Protein C (P < .001), PrS (P < .001) and AT (P < .001) levels were lower in cirrhotics compared with noncirrhotics. In addition, patients with Child-Pugh (CP)-C had significantly lower (P < .05) functional PrC, PrS and AT levels than CP-B, CP-A and noncirrhotic patients. Low PrC function correlated with markers of liver dysfunction and inflammation: INR(r = -.72, P < .001), bilirubin (r = -.620, P < .001), albumin (r = .539, P < .001), creatinine (r = -.417, P < .001), ferritin (r = -.68, P = .035), procalcitonin (r = -.79, P = .01), raised ESR (r = .56, P < .001) and liver fibrosis (r = -.840, P < .001). Patients who died (n = 160) had significantly lower median PrC function (23.8%, 16.3-33.0]) compared with those who remained alive (74.9%, [59.7-92.5]); P < .001. In a multivariable predictive model using PrC, and MELD score, we found a significant impact of low PrC levels on survival (P < .001, IRR = 0.97, 95% CI = 0.96-0.98). Receiver operating characteristic (ROC) curve analysis revealed that functional PrC levels <52% were associated with increased mortality (P < .001).

CONCLUSION:

Low functional protein C level correlated with markers of liver dysfunction, inflammation and sepsis and independently predicted mortality at 3 months in cirrhotics, especially if functional levels were <52%.

• Authors: A G Patil, C Bihari, H D Shewade, N Nigam, S K Sarin
• Journal: International journal of laboratory hematology (Int J Lab Hematol) Vol. 40 Issue 4 Pg. 466-472 (Aug 2018) ISSN: 1751-553X [Electronic] England
• PMID: 29704446 (Publication Type: Journal Article)
• Copyright: © 2018 John Wiley & Sons Ltd.

Chemical References

• Biomarkers
• Protein C
• Protein S
• Antithrombin III

Topics

• Adult
• Aged
• Antithrombin III (analysis)
• Biomarkers (blood)
• Case-Control Studies
• Female
• Humans
• Liver Cirrhosis (blood, diagnosis)
• Male
• Middle Aged
• Predictive Value of Tests
• Prognosis
• Protein C (analysis)
• Protein S (analysis)
• ROC Curve