BiomarkersEvaluation of hemostatic biomarker abnormalities that precede platelet count decline in critically ill patients with sepsis☆,☆☆
Introduction
Coagulation and fibrinolytic abnormalities are observed in most patients with sepsis [1]. Severe inflammation in sepsis is associated with tissue factor–mediated activation of coagulation, which leads to thrombin generation and results in widespread fibrin deposition. The severity of coagulopathy in sepsis ranges from subclinical abnormalities, which are detectable by a mild increase in fibrin degradation products (FDPs) and prolongation of global clotting times, to fulminant disseminated intravascular coagulation (DIC), characterized by widespread microvascular thrombosis [2]. A number of studies have reported on the association between DIC and organ failure and found that DIC is an independent risk factor for mortality in patients with sepsis [2], [3], [4], [5]. Early diagnosis and treatment may therefore improve outcomes in septic patients with DIC [6].
The International Society on Thrombosis and Haemostasis (ISTH) criteria are currently widely used for diagnosing DIC [7] and are a strong independent predictor of mortality in patients with severe sepsis [8]. Although the ISTH criteria for overt DIC are simple and clinically useful, they have some limitations to be applied for early stage of DIC. The ISTH criteria define nonovert DIC as the stage before overt DIC, for the purpose of early diagnosis [7]. However, previous studies have shown that few patients with nonovert DIC progress to overt DIC and that mortality rates are similar between patients with nonovert DIC and patients with overt DIC [8], suggesting that septic coagulopathy diagnosed according to the ISTH criteria for nonovert DIC may not necessarily be an early stage of overt DIC.
Previous studies have evaluated a number of hemostatic biomarkers including d-dimer, antithrombin (AT), thrombin-AT complex (TAT), plasmin–α2-plasmin inhibitor complex (PIC), and plasminogen activator inhibitor-1 (PAI-1); however, no single marker that can effectively diagnose early stage of DIC has been identified [9], [10]. It is therefore important to develop clinical markers that can detect progression of septic coagulopathy in initial phase, so that early intervention can be instituted.
The objective of this study was to evaluate the ability of hemostatic biomarkers for predicting progression of coagulopathy in septic patients admitted to the intensive care unit (ICU). We used a decrease in platelet count as a marker for overt stage of septic coagulopathy. Platelet activation, consumption, and destruction may occur at the endothelial cell surface as a result of thrombin generation and fibrin meshwork formation secondary to coagulation activation. Platelet count decreases over a few days after the development of sepsis [5], which may indicate ongoing activation of coagulation [11]. Thrombocytopenia may reflect the advanced stage of DIC, which is associated with late death in patients with severe sepsis [5], [12]. We therefore considered that a decreasing platelet count could be an indicator of disease progression in sepsis-induced coagulopathy.
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Patients
The medical records of all patients admitted to the ICU at Jichi Medical University Hospital from September 2010 to December 2011 were retrospectively reviewed. Patients with a diagnosis of sepsis and a platelet count of more than 80 × 103/μL on the day of ICU admission were included in the study. Sepsis was defined as fulfillment of at least 2 of the 4 criteria for systemic inflammatory response syndrome [13] and proven or suspected infection. Exclusion criteria were as follows: age younger
Characteristics of the 75 eligible patients with sepsis
Of the 1343 patients admitted to the ICU during the study period, 108 had a diagnosis of sepsis on the day of ICU admission. Thirty-three patients were excluded according to the study criteria, and the remaining 75 patients were included in the study. Forty-two patients developed a subsequent decrease in platelet count within 5 days of ICU admission (Fig. 1).
Table 1 shows the baseline characteristics of the 75 patients. The most common cause of sepsis was abdominal infection, including 26
Discussion
In this retrospective study, we evaluated the usefulness of a single measurement of coagulation and fibrinolytic biomarkers on the day of ICU admission, for providing simple and prompt assessment for progression of coagulopathy in patients with sepsis. Our results show that decreased PC and α2-PI activity were strong predictors of a subsequent decrease in platelet count, which was considered as an indicator of overt coagulopathy in sepsis.
Currently, there are no widely accepted diagnostic
Acknowledgments
The authors thank the nursing staff of the ICU at Jichi Medical University Hospital for their assistance.
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Comparison of point-of-care hemostatic assays, routine coagulation tests, and outcome scores in critically ill patients
2015, Journal of Critical CareCitation Excerpt :In survivors, this decrease is followed by a compensatory increase above baseline values. This reactive thrombocytosis either recovers back to baseline or is missing in nonsurvivors [25,33]. A similar pattern could be detected in this study.
Clinical syndromes associated with acquired antithrombin deficiency via microvascular leakage and the related risk of thrombosis
2014, Thrombosis ResearchCitation Excerpt :Regardless of the mechanism, AT deficiency is invariably present in severe sepsis and the level correlates with severity of illness and clinical outcome [43–45,164–167]. Indeed, AT depletion has been related to a pre-DIC state [161,163,164,168]. Some recent data from clinical studies suggest that AT replacement therapy in patients with septic shock may shorten the duration of DIC, reduce organ dysfunction and improve survival [164,169–174].
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Authors' contributions: K.K. conceived and designed the study. K.K. and S.T. prepared the data for analysis. K.K. conducted the data analysis. S.M. assisted with interpretation of the results. Y.S., J.M., and S.N. supervised the study. K.K. and S.M. drafted the article. All authors read and approved the manuscript. K.K. and S.M. take responsibility for the manuscript as a whole.
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Conflict of interest statement: The authors declare that they have no conflicts of interest.