High Mobility Group Box chromosomal protein 1 (HMGB1) is a nuclear DNA-binding protein acting as a proinflammatory cytokine when released in the extracellular space from necrotic cells,activated macrophages and dendritic cells. HMGB1 acts on a specific receptor, RAGE (receptor for advanced glycation end-products), and induces prolonged inflammation, organ failure, septicaemia and death. The aim of the study was to determine the diagnostic value of plasma HMGB1 concentration and its role in the development of organ failure in patients with disseminated intravascular coagulation (DIC). Plasma HMGB-1 levels were measured in patients with suspected DIC and their relationships with DIC, organ failure and clinical outcome were determined. The study took place at the intensive care facility, Mie University School of Medicine and comprised 201 patients with suspected DIC. Plasma HMGB1 was below the detection limit in normal subjects, but moderately elevated in patients with infectious diseases (4.54 +/- 8.18 ng/ml, mean +/- SD), malignancies (2.15 +/- 5.34 ng/ml),and traumas (6.47 +/- 13.13 ng/ml). DIC was associated with significantly high plasma HMGB1 (14.05 +/- 12.56 ng/ml) in these patients. The highest HMGB1 levels were in patients with organ failure (8.29 +/- 10.99 ng/ml) and non-survivors (16.58 +/- 11.01 ng/ml). HMGB1 plasma levels correlated with the DIC score and sepsis-related organ failure assessment (SOFA) score. In conclusion, our data suggest that HMGB-1 is a potentially suitable prognostic marker of OF or DIC.

Summary.  Background: Fibrin‐related markers such as soluble fibrin (SF) and D‐dimer are considered useful for the diagnosis of thrombosis. However, the evidence for diagnosis of thrombosis by fibrin‐related markers is not well‐established. Objective: To evaluate the cutoff values of D‐dimer and SF in the diagnosis of thrombosis. Patients and Methods: Plasma concentrations of SF and D‐dimer were measured in 784 inpatients suspected of having thrombosis between 1 August 2003 and 31 December 2004, and then correlated with thrombosis. Results and Conclusions: Plasma concentrations of D‐dimer and SF were significantly higher in patients with disseminated intravascular coagulation (DIC), deep vein thrombosis (DVT) and cerebral thrombosis, compared with those in patients without thrombosis. When cutoff values of > 3.0 μg mL−1 for D‐dimer and > 6.0 μg mL−1 for SF were used for the diagnosis, more than 50% of patients (with the exception of liver transplant patients and postoperative patients) had thrombosis. Receiver operating characteristic analysis showed that SF was more useful than D‐dimer for the diagnosis of thrombosis (i.e. DVT and DIC). The cutoff value of D‐dimer (7.87 μg mL−1) was the same for DVT and DIC, while that of SF was slightly lower for DVT (7.05 μg mL−1) than for DIC (8.60 μg mL−1). Our findings suggest that high levels of plasma fibrin‐related markers reflect high risk for thrombosis.

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There are three different diagnostic score systems for disseminated intravascular coagulation (DIC) established by the Japanese Ministry Health and Welfare (JMHW), the International Society on Thrombosis and Haemostasis (ISTH) and the Japanese Association for Acute Medicine (JAAM). The JMHW criteria are still used in Japan. In the present study, all three diagnostic criteria were used to prospectively evaluate 413 patients with different underlying diseases of DIC who were treated at the Mie University Hospital (JMHW, n= 166; ISTH, n=143; JAAM, n=291). The odds ratio (95% confidence interval) for death was 1.88 (1.22 - 2.90) in JMHW, 2.55 (1.65 - 3.95) in ISHT and 1.99 (1.19 - 3.32) in JAAM. The platelet count, prothrombin time, fibrin and fibrinogen degradation products and fibrinogen were significantly important for diagnosis of DIC by all three diagnostic criteria. Haemostatic molecular markers were significantly high in all patients and were useful for the diagnosis of DIC. The JAAM diagnostic criteria displayed a high sensitivity for DIC and the ISTH overt-DIC diagnostic criteria displayed a high specificity for DIC. All three diagnostic criteria for DIC were related to a poor patient outcome.

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Up-regulation of the IL-1-IL-6 network stimulates systemic expression of C-reactive protein (CRP). This cytokine network system plays a pivotal role in inducing angiogenic growth factors in intestinal mucosa. Serum CRP level and tissue concentrations of cytokines in colorectal cancer patients were determined and an in vitro model was employed to determine the time course of induction of IL-6 in Caco-2 cells. Increased serum CRP was associated with recurrent disease and shorter survival time. Intense surgical stress and the presence of an acute phase reactant were independently associated with overexpression of IL-6 in the tumor. Enhanced IL-6 protein expression in Caco-2 cells induced by the initial treatment with IL-1beta or lipopolysaccharide could be abrogated by additional presupplementation of IL-1ra. The presence of an acute phase reactant reflects uncontrolled up-regulation of the local IL-1-IL-6 network system in the tumor, which may enhance the survival and proliferation of remnant cancer cells after tumor resection.

Prothrombin fragment 1 + 2 (F1 + 2) is considered to be useful for diagnosis of thrombosis. However, the evidence for a diagnosis of thrombosis by F1 + 2 is still not well established. The plasma concentrations of F1 + 2, soluble fibrin, D-dimer, and thrombin-antithrombin complex were measured in 694 patients suspected of having thrombosis and then were correlated with thrombosis. Plasma concentrations of F1 + 2, soluble fibrin, D-dimer, and thrombin-antithrombin complex were significantly higher in patients with thrombosis, compared with patients without thrombosis. When cutoff values of more than 300 pmol/L for F1 + 2 were used for the diagnosis, more than 50% of the patients were thus found to have thrombosis. The findings showed that F1 + 2, soluble fibrin, D-dimer, and thrombin-antithrombin complex have similar diagnostic ability. The plasma concentration of F1 + 2 closely was well correlated with thrombin-antithrombin complex, soluble fibrin, and D-dimer. Finally, F1 + 2 is one of the most useful parameters for the diagnosis of thrombosis.

Procalcitonin (PCT) is a marker of severe bacterial infections and organ failure due to sepsis. The purpose of the present study was to identify the appropriate cutoff level of PCT based on the findings of a blood culture and polymerase chain reaction (PCR). The PCT levels were measured in 116 patients in an intensive care unit who were suspected of having bacteremia, to examine its relationship with a blood culture or PCR. The PCT levels were significantly high in patients with bacteremia, but they were also moderately high in some patients who were positive for fungus DNA. The area under the curve was significantly higher for PCT than for C-reactive protein. The appropriate cutoff values of PCT for bacteremia were 0.38 microg/L for the high negative predictive value and 0.83 microg/L for the high positive predictive value. Procalcitonin was slightly related to mortality, and the combination of a blood culture and PCR was thus found to increase the sensitivity for mortality. These findings suggest that PCT is useful for the diagnosis of bacteremia and that the diagnostic value of PCT in combination a with blood culture and PCR for bacterial infection or mortality further increases.