It has been generally accepted that during microorganism infection, inflammation and coagulation are involved in the development of septic complications, and mainly characterized by inflammation in early stage and obvious coagulation disorders in middle or the late stage. It may be helpful to accurately predict the coagulation condition according to the early inflammatory indicators. Our data revealed that lactate, APACHEII score and total bilirubin are independently associated with DIC development subsequently with sepsis shock, and procalcitonin improved the prediction of DIC induced by septic shock with critical ill patient. Combined procalcitonin (inflammation biomarker) with other risk factors could improve the predictive performance of disseminated intravascular coagulation (DIC) development in sepsis shock patients. Our results may offer a potential screening tool for physicians to assess the chances of DIC development at early stage of septic shock.
Notably, more than 30 million people are affected by sepsis worldwide and the incidence has been increasing over the past several decades, though the mortality has declined significantly with the advancement of diagnosis and management of sepsis (21–23). One of the most frequently encountered complications is the occurrence of DIC, which is the hallmark of the failure of hemostatic system (24). Currently, there are three guidelines for diagnosis and treatment of DIC that have been published (9–11). Although those three guidelines are generally similar, they have some key differences. Therefore, the ISTH integrated those three guidelines and published its own guidance of diagnosis and treatment for DIC(25), which has been accepted as the international standard and was used in this study. Moreover, ISTH overt-DIC score has also been used to screen DIC on ICU day 1, which was shown to be associated significantly decreased mortality in a multicenter retrospective cohort (26). However, no single parameter has been reported to effectively predict DIC in septic shock patients.
Lactate is an anerobic metabolite that is commonly used as a marker for the function of microcirculation. During the early development of DIC, the excessive formation of microthrombi occludes the blood supply and causes tissue hypoxia, then eventually results in dysfunction of microcirculation and elevation of lactate level. Additionally, another study has shown that increased lactate level could predict the 90-day mortality of septic patients with DIC(15). Thus, lactate level elevation may reflect the early stage of DIC development, as evidenced by our finding that lactate level was an independent risk factor for DIC.
Bilirubin is a biochemical indicator of liver function. Hyperbilirubinemia(hepatic dysfunction) is not uncommonly observed in patients with severe sepsis(27). However, literatures on the study of hyperbilirubinemia in sepsis were very limited. Data form one retrospective study indicated that elevated serum bilirubin levels within 72 hours of admission were associated increased mortality in patients with severe sepsis and septic shock (28). In our study, we identified serum bilirubin as an independent risk factor for development of DIC in septic shock patients. The mechanisms of this correlation are multifaceted and warrant further investigation. One plausible explanation would be that elevated serum bilirubin is a marker of liver dysfunction which is aggravated by DIC development.
PCT was reported as a biomarker of infection and sepsis and higher level of PCT was associated with higher serum proinflammatory cytokines(16, 20), and such proinflammatory mediators could potently contribute to occurrence of coagulopathy through various mechanisms(29). Significantly higher PCT level was also observed in septic patients with DIC compared to those without (16, 30). Our study revealed that PCT level in sepsis shock patients was significantly associated with risk of subsequent development of DIC, independent of conventional risk factors including lactate, APACHEII score and total bilirubin. More importantly, combining PCT with other risk factors significantly improve the capability to predict the subsequent development of DIC in sepsis shock patients, and close monitoring of PCT level may help to guide the use of anticoagulants in early stage of DIC for intensivists.
Several aspects of limitations present in our study should be noted. Firstly, this is a retrospective study based on a small population at single center. Secondly, although we tried to adjust the potential bias, other unknown factors may also confound our results. Thirdly, this is a preliminary study to explore the potential association between PCT and DIC development in septic shock patients and large multicenter prospective studies are needed to confirm our findings.
In conclusion, our study revealed an unappreciated clinical value of PCT in prediction of DIC development in septic shock patients. Better predictive performance could be obtained by integrating the PCT with conventional risk factor.