Disseminated intravascular coagulation (DIC) is characterised by thrombotic occlusion and bleeding (12). Although the diagnosis of DIC is important for patients in the medical intensive care unit (ICU), no single laboratory test with satisfactory performance for the accurate diagnosis of DIC is currently available (3). Currently, the most commonly used diagnostic criteria for DIC are the International Society on Thrombosis and Haemostasis (ISTH) criteria, the Japanese Association for Acute Medicine (JAAM) criteria and the Japanese Ministry of Health and Welfare (JMHW) (4). In 1993, the Korean Society on Thrombosis and Hemostasis (KSTH) also developed diagnostic criteria for DIC (5). However, the performance of KSTH diagnostic criteria has not yet been validated and not accepted as commonly used DIC diagnostic criteria.

Although previous studies showed that the Japanese criteria (JAAM and Revised-JAAM [R-JAAM]) possess higher sensitivity than both ISTH and JMHW criteria (67), these studies have some statistical bias such as overlap of subgroup that the DIC patients diagnosed from JAAM and R-JAAM criteria included the majority of DIC patients diagnosed from the ISTH criteria. Several studies also evaluated the prognostic impact of various DIC criteria based on the acute physiology and chronic health evaluation (APACHE) II score, the sequential organ failure assessment (SOFA) score, and mortality (78910). However, most of these studies included heterogeneous patient cohort and few studies addressed the prognostic impact of various DIC diagnostic criteria in specific patient subgroup with severe sepsis and septic shock. In the present study, we aimed to compare the performance of five DIC diagnostic criteria focused on the mortality prediction as an outcome parameter in patients with severe sepsis or septic shock, while including the KSTH criteria.

We compared the ability of five sets of DIC diagnostic criteria, including the non-validated KSTH criteria, to predict overall ICU and 28-day mortality in patients with severe sepsis or septic shock. Our present study showed that both KSTH and JMHW criteria possess superior performance than the ISTH, JAAM and R-JAAM criteria in the prediction of overall ICU and 28-day mortality.

Several guidelines for the diagnosis of DIC were published. Di Nisio et al. (4) recommended the use of the ISTH, JMHW or JAAM criteria. Levi et al. (3) used ISTH criteria and evaluated mortality to judge the efficacy of the DIC criteria. On the other hand, Wada et al. (1213) recommended the JAAM criteria while emphasizing the importance of early diagnosis and treatment. Although the KSTH DIC scoring system has the advantage of being concise and relatively easy to use for calculations without a weighted score, the KSTH criteria are currently not accepted as an international diagnostic method due to a lack of clinical application data. However, a previous study compared the KSTH criteria and ISTH criteria, and reported a K-coefficient of 0.78 (6). Moreover, a study by Lee et al. (5) reported a concordance rate of 84.7% and K-coefficient of 0.6 between the ISTH criteria and KSTH criteria, and concluded that the KSTH criteria is more sensitive predictor of mortality than the ISTH criteria. In the present study, we found a similar concordance rate (88.0%) and K-coefficient (0.76) which is higher than the earlier reported concordance rate for the ISTH/JMHW criteria (67.4%) (14) and the ISTH/JAAM criteria (86.5%) (15).

The patient cohort in the present study who were diagnosed as DIC according to the ISTH, JMHW and JAAM criteria on day 1–4 showed a similar distributions to that reported previously. Gando et al. (67) and Hayakawa et al. (15) reported that the JAAM criteria is the most sensitive diagnostic criteria for the diagnosis of septic DIC, whereas the ISTH criteria are the most specific. Similarly, our present results showed that DIC cases diagnosed according to the JAAM criteria included all patients diagnosed as DIC according the KSTH, JMHW and ISTH criteria. However, our study showed higher incidence of DIC than result of Gando et al. (16) for patients with severe sepsis or septic shock (JAAM DIC 69% vs. 46.8%). We hypothesize that enrollment of patients having more severe severity in our present study may be attributable to this result (septic shock 70% vs. 45%, APACHE II score 24.7 vs. 23.2, SOFA score 10.5 vs. 8.5, respectively).

Many studies showed that these characteristics above mentioned of each DIC criteria are reflected by the extent of mortality. Gando et al. (6) reported that the prediction rates of mortality using the ISTH criteria (51.9%) and JMHW (50.0%) are higher than those predicted by the JAAM criteria (43.8%). Takemitsu et al. (17) reported a similar performance between these two sets of criteria in terms of predicting mortality. The mortality rates predicted by the ISTH, JMHW and JAAM criteria in that study were 40.6%, 35.5% and 31.7%, respectively. The sensitivity/specificity of the ISTH, JMHW and JAAM criteria for the prediction of mortality were 50.4%/71.4%, 51.3%/64.9%, and 80.0%/33.2%, respectively. Our present study showed similar results that both ISTH and JMHW criteria are more specific than the JAAM criteria in the prediction of overall ICU mortality. Our present study found the sensitivity/specificity of the ISTH, JMHW and JAAM criteria for predicting mortality as 48.4%/75.4%, 77.4%/62.3% and 71.0%/52.2%, respectively, when applied at Day 1.

Few studies have used logistic regression and ROC analysis to evaluate the DIC diagnostic criteria and mortality outcomes. Angstwurm et al. (10) analysed ISTH criteria for the prediction of mortality using the ROC analysis, and reported AUC of 0.735. Gando et al. (8) applied logistic regression analysis in the evaluation of the JAAM criteria on the prediction of mortality and reported OR of 1.223. Iwai et al. (9) reported that only the APACHE II score is independently associated with mortality (P < 0.001, OR 1.21); however, the JAAM criteria also showed a low, non-significant OR for the prediction of mortality after the removal of confounding factors (P = 0.066, OR 0.29). Recently, Gando et al. (16) reported that the JAAM criteria applied at day 1 (OR 1.282, P < 0.001) and the Delta JAAM DIC score applied at day 1 (OR 0.770, P < 0.001) are independent predictors of 28-day mortality in DIC patients with severe sepsis. In the present study, the delta DIC score did not predict ICU mortality significantly, but tended to reduce mortality when the delta score increases. However, our present study demonstrated that both KSTH and JMHW criteria applied on Day 1 and overall period significantly predicted the overall ICU mortality. Kaplan-Meier curve analysis also showed that the ability of the KSTH and JMHW criteria on Day 1 and overall period to predict 28-day mortality was significantly high.

The possible explanations for these results are as follows: first, fibrinogen is an acute phase protein increased during inflammatory responses. Therefore, in certain situation that DIC is accompanied by inflammation, we would expect that a decrease in fibrinogen levels in DIC can be masked by the increase of fibrinogen level due to inflammatory process. Bakhtiari et al. (18) reported that exclusion of fibrinogen level from the ISTH DIC score would not affect the accuracy of scoring system in the detection of DIC in critically ill patients. Gando et al. (7) made the R-JAAM criteria based on the little effect of fibrinogen level on the prediction of outcome in the DIC patients. However, Kim et al. (19) showed that the OR of the low fibrinogen level (< 1.0 g/L) is 2.13 (P = 0.024) and Gando et al. (16) reported that the fibrinogen is an independent predictor for 28-day mortality (OR 0.998, P = 0.033). The present study showed that fibrinogen on Day 1 transformed to nominal variable is an independent predictor for ICU mortality in univariable analysis. Especially, the KSTH criteria showed the best statistical significance (P = 0.007, OR 9.479, 95% CI 1.839–48.853).

Second, only the KSTH criteria included the aPTT as a variable. Our present study showed that the aPTT (P = 0.042, OR 1.024, 95% CI 1.001–1.048), D-dimer (P = 0.042, OR 1.037, 95% CI 1.001–1.075), and platelet (P = 0.002, OR 0.988, 95% CI 0.981–0.996) except PT (P = 0.083, OR 1.061, 95% CI 0.992–1.134) were risk factors for ICU mortality. In additional analysis using nominal variable of marker transformed by the KSTH criteria, aPTT was a more useful marker for ICU mortality than PT (P = 0.027, OR 2.705, 95% CI 1.121–6.527 vs. P = 0.286, OR 1.629, 95% CI 0.665–3.990, respectively) (data not shown). We assumed the reason for these results. First, a prolonged PT, which reflects the inhibition of hemostasis cascade from the release of tissue factor (extrinsic pathway), happens faster than a prolonged aPTT which is related to the inhibition of intrinsic pathway. Second, at the early stage of sepsis, factor VIII levels are likely to be increased because factor VIII is an acute phase reactant. As a result, the prolongation of aPTT may be masked by an increase in factor VIII levels in early sepsis patients with DIC. Kinasewitz et al. (20) and Kim et al. (19) reported that the abnormality rate in PT is hihger than that in aPTT (93.4% vs. 63.1% and 68.4% vs. 47.3%, respectively) for patients with sepsis. In conclusion, we suggest that PT is an early marker for the detection of DIC, and aPTT is a marker for the reflection of severity in DIC.

Our present study had certain limitations. First, our small sample size would be main limitation. We could not calculate appropriate sample size due to lack of previous study comparing DIC diagnostic criteria in the prediction of mortality in patients with severe sepsis or septic shock. Unavoidably, our present pilot study included small number of patients compared with other studies. Second, single center design for clarification and generalization of analysis results would be another limitations. More comprehensive and well-designed multicenter prospective study focused on this issue should be performed. Third, our present study limited study population as patients with severe sepsis or septic shock and possible selection bias may affect the study results. Especially, as previously discussed, it is needed to consider that our present study enrolled more severe septic patients. More comprehensive study in the DIC patients caused from other diseases should be required for the generalization of our present study results. In addition, although our present study showed higher AUC values of KSTH and JMHW criteria than other three criteria, AUC values of all five criteria were below 0.7, which may remain a concern that these level can be regarded as an adequate evidence of diagnostic value. Therefore, we suggest that clinicians should be warned not to predict prognosis entirely based on the DIC criteria.

In conclusion, our present study showed that both KSTH and JMHW criteria would be more useful than other three criteria in predicting prognosis in DIC patients with severe sepsis or septic shock, and more comprehensive study would be required for the confirmation of our present study results.