Intern Med. 2013;52(17):1893-8.

A prospective analysis of disseminated intravascular coagulation in patients with infections.

Seki Y, Wada H, Kawasugi K, Okamoto K, Uchiyama T, Kushimoto S, Hatada T, Matsumoto T, Imai H; Japanese Society of Thrombosis Hemostasis/DIC Subcommittee.

Department of Internal Medicine, Shibata Hospital-Niigata Prefectural Hospital, Japan.

 

Abstract

OBJECTIVE: Disseminated intravascular coagulation (DIC) is often associated with infection and a poor outcome. In this study, useful markers for predicting poor outcomes were examined.

METHODS: The frequency of DIC and organ failure, outcomes and hemostatic markers were prospectively evaluated in 242 patients with infections.

RESULTS: Seventy-seven patients were diagnosed with DIC, 36 of whom recovered from the condition. The rate of DIC or resolution of DIC was highest in the patients with sepsis and lowest in the patients with respiratory infections. Mortality tended to be high in the patients with respiratory infections. The DIC score, sepsis-related organ failure assessment (SOFA) score, prothrombin time (PT) ratio and thrombin-antithrombin complex level were significantly high in the patients who did not recover from DIC. The age, DIC score, SOFA score, PT ratio and levels of thrombomodulin and plasminogen activator inhibitor (PAI)-I were significantly high in the non-survivors. Factors related to a poor outcome included resolution of DIC, the SOFA score, age and the PT ratio. Factors related to resolution of DIC included the SOFA score and age, while factors related to the SOFA score included the levels of PAI-I, leukocytes, fibrinogen, D-dimer and platelets.

CONCLUSION: The outcomes of septic patients primarily depend on the SOFA score and the resolution of DIC, which are related to organ failure.

PMID: 23994978

 

SUPPLEMENT:

 This report is one of several analyses of disseminated intravascular coagulation (DIC) which have been reported by the Japanese (DIC) Study Group on the Scientific and Standardization Committee (SSC) Meeting/International Society of Thrombosis and Haemostasis (ISTH, Figure 1). DIC is frequently observed in patients with infections [1, 2]. Bleeding symptoms are rare, whereas organ failure is more often observed in patients with infectious DIC compared to those with leukemic DIC. A hypercoagulable state and microvascular dysfunction, including decreased levels of antithrombin (AT) and protein C (PC) and elevated levels of thrombomodulin (TM) and plasminogen activator inhibitor I (PAI-I), are frequently present in those patients [3, 4] and reduced amounts of AT and PC result in a lack of inhibition of thrombin and activated coagulation factor VIII, respectively.

figure 1Figure 1, The ISTH/SSC meeting subcommittee on DIC

The abnormalities of the hemostatic system in patients with DIC result from the effects of both vectors for hypercoagulation and hyperfibrinolysis (Figure 2) [5]. Hypercoagulation without hyperfibrinolysis is usually observed in patients with infectious DIC. The outcomes of DIC are poorer in patients with infections than in patients with leukemia. The poor outcome of infectious DIC is dependent on organ failure. The degree of organ failure is evaluated according to the sepsis-related organ failure assessment (SOFA) score or the acute physiological and chronic health evaluation (APACHE) II score. Although several randomized controlled trials of treatment for severe sepsis and/or DIC [6-9] have been conducted, few successful results have been obtained [7, 9].

figure 2Figure 2, The hemostatic abnormalities associated with infectious DIC

In this study of DIC caused by infection, the frequency of DIC was 31.8%, the rate of resolution of DIC was 46.8% and the mortality rate of DIC was 44.2%. The high mortality of the patients with infection-related DIC is similar to that reported in various previous studies. Among the patients with infections, the frequency of DIC was highest in those with sepsis, thus suggesting that the systemic inflammatory response syndrome (SIRS) scores are high and leukocytes and vascular endothelial cells are activated in patients with severe sepsis. The patients with DIC caused by respiratory infections exhibited the lowest rate of resolution of DIC and the highest mortality rate. Under these conditions, acute lung injury and acute respiratory distress syndrome frequently occur, which thus results in poorer outcomes. The rate of resolution of DIC was the highest in the patients with sepsis without other infections, thus suggesting that this condition includes many catheter infections that do not lead to organ failure in the early stage of infectious DIC.

There were significant differences in the levels of hemostatic molecular markers between the patients with and without DIC. The differences in the levels of thrombin-AT complex (TAT) between the patients with and without DIC tended to be smaller than those of soluble fibrin monomer complex (SFMC) due to the decreased levels of AT in the patients with sepsis [10]. The DIC score, SOFA score, prothrombin time (PT) ratio and TAT level were significantly higher in the patients who did not recover from DIC than in those who did, suggesting that the resolution of DIC depends on the severity of DIC. These analyses indicate that the organ failure and hemostatic abnormalities caused by DIC interact. The age, DIC score, SOFA score, PT ratio and levels of TM and PAI-I were all significantly higher in the non-survivors than survivors, again suggesting that the outcomes of DIC depend on the persistence of DIC and the degree of organ failure. DIC worsens organ failure, and the deterioration of organ failure increases the DIC score.

In conclusion, the outcomes of septic patients depend on the resolution of DIC, which is related to the presence of multiple organ failure.

 

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