Department of Clinical Haematology, Institute of Liver & Biliary Sciences, New Delhi, India.
South-East Asia Office, International Union Against Tuberculosis and Lung Disease (The Union), New Delhi, India.
Int J Lab Hematol. 2018 Aug;40(4):466-472. doi: 10.1111/ijlh.12836. Epub 2018 Apr 28.
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.
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.
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).
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%.
蛋白 C（PrC）是一种生理性抗凝剂，可调节炎症和细胞死亡，在败血症中具有已知的预测/治疗作用。越来越多的证据表明，血浆高凝状态导致纤维化进展和微血栓形成，从而导致终末器官功能障碍。我们研究了天然抗凝剂——蛋白 C（PrC）、蛋白 S（PrS）和抗凝血酶 III（AT）——与肝硬化患者临床结局之间的可能关联。
分析了 515 例肝硬化患者和 229 例非肝硬化患者的功能性 PrC、PrS 和 AT，并进行了比较。在这些肝硬化患者中，我们进行了 3 个月生存率的多变量预测模型，以评估抗凝剂的预后能力。
与非肝硬化患者相比，肝硬化患者的蛋白 C（P<0.001）、PrS（P<0.001）和 AT（P<0.001）水平较低。此外，CP-C 患者的功能性 PrC、PrS 和 AT 水平明显低于 CP-B、CP-A 和非肝硬化患者（P<0.05）。低 PrC 功能与肝功能和炎症标志物相关：INR（r=-0.72，P<0.001）、胆红素（r=-0.620，P<0.001）、白蛋白（r=-0.539，P<0.001）、肌酐（r=-0.417，P<0.001）、铁蛋白（r=-0.68，P=0.035）、降钙素原（r=-0.79，P=0.01）、升高的 ESR（r=-0.56，P<0.001）和肝纤维化（r=-0.840，P<0.001）。死亡（n=160）患者的中位 PrC 功能（23.8%，16.3-33.0%）明显低于存活患者（74.9%，59.7-92.5%）（P<0.001）。在使用 PrC 和 MELD 评分的多变量预测模型中，我们发现低 PrC 水平对生存率有显著影响（P<0.001，IRR=0.97，95%CI=0.96-0.98）。接受者操作特征（ROC）曲线分析显示，功能性 PrC 水平<52%与死亡率增加相关（P<0.001）。
低功能性蛋白 C 水平与肝功能障碍、炎症和败血症的标志物相关，在肝硬化患者中独立预测 3 个月时的死亡率，特别是功能性水平<52%时。
