Disseminated Intravascular Coagulation Group Research Articles

Disseminated intravascular coagulation is associated with poor prognosis in patients with COVID-19

This study aimed to investigate the incidence and significance of disseminated intravascular coagulation (DIC) in coronavirus disease 2019 (COVID-19). A multicenter cohort study was conducted using large-scale COVID-19 registry data. The patients were classified into DIC and non-DIC groups based on the diagnosis on admission (day 1) and on any of the days 1, 4, 8, and 15. In total, 23,054 patients were divided into DIC (n = 264) and non-DIC (n = 22,790) groups on admission. Thereafter, 1654 patients were divided into 181 patients with DIC and 1473 non-DIC patients based on the DIC diagnosis on any of the days from 1 to 15. DIC incidence was 1.1% on admission, increasing to 10.9% by day 15. DIC diagnosis on admission had moderate predictive performance for developing multiple organ dysfunction syndrome (MODS) on day 4 and in-hospital death and was independently associated with MODS and in-hospital death. DIC diagnosis on any of the days from 1 to 15, especially days 8 and 15, was associated with lower survival probability than those without DIC and showed significant association with in-hospital death. In conclusion, despite its low incidence, DIC, particularly late-onset DIC, plays a significant role in the pathogenesis of poor prognosis in patients with COVID-19.

Overt disseminated intravascular coagulation and antithrombin III predict bleeding and in-hospital mortality in patients undergoing extracorporeal membrane oxygenation.

Limited data are available on the relationship of disseminated intravascular coagulation (DIC) with mortality in patients receiving extracorporeal membrane oxygenation (ECMO). Thus, we investigated the association of DIC score and antithrombin (AT) III with clinical outcomes in patients undergoing ECMO. We analyzed 703 patients who underwent ECMO between January 2014 and May 2022 at Samsung Medical Center. The DIC score was calculated using laboratory findings within 24 h of the ECMO initiation, and ≥ 5 was defined as overt DIC. In addition, the AT III level was measured to identify the correlation with the DIC score. Among the study patients, 169 (24.0%) were diagnosed with overt DIC (DIC group) during early maintenance therapy. In-hospital mortality was significantly higher in the DIC group than in the non-DIC group (55.0% vs. 36.5%, p < 0.001). Bleeding events were significantly higher in the group of patients with a DIC score of 7 or 8 than in the other group (20.8% vs. 8.4%, p = 0.038). DIC score negatively correlated with AT III level (r = -0.417, p < 0.001). The predictive performance of AT III for overt DIC had statistical significance with a c-static of 0.81 (95% confidence interval (CI), 0.77-0.84, p < 0.001). Overt DIC was associated with higher in-hospital mortality and a tendency to bleed in ECMO patients. Furthermore, AT III plasma levels can easily predict overt DIC in patients undergoing ECMO. These findings suggest that monitoring AT III plasma levels may be important in the management of ECMO.

Microparticle-associated tissue factor activity correlates with the inflammatory response in septic disseminated intravascular coagulation patients.

Sepsis is often accompanied by the formation of disseminated intravascular coagulation (DIC). Microparticles can exert their procoagulant and proinflammatory properties in a variety of ways. The purpose of this study was to investigate the relationship between microparticle-associated tissue factor activity (TF+-MP activity) and the inflammatory response. Data from a total of 31 DIC patients with sepsis and 31 non-DIC patients with sepsis admitted to the ICU of the First Affiliated Hospital of Harbin Medical University from December 2017 to March 2019 were collected. Blood samples were collected and DIC scores were calculated on the day of enrollment. The hospital's clinical laboratory completed routine blood, procalcitonin, and C-reactive protein tests. TF+-MP activity was measured using a tissue factor-dependent FXa generation assay. Interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) levels were determined using ELISA kits. Compared with the non-DIC group, the DIC group had higher levels of leukocytes, neutrophils, procalcitonin, C-reactive protein, IL-1β, and TNF-α, and more severe inflammatory reactions. TF+-MP activity in the DIC group was higher than that in the non-DIC group. In sepsis patients, TF+-MP activity was strongly correlated with inflammatory response indices and DIC scores. TF+-MP activity may play a major role in promoting inflammatory response in septic DIC.

The Proactive Diagnostic Value of Thrombin-Antithrombin Complex and Antithrombin III in Disseminated Intravascular Coagulation

Introduction Disseminated intravascular coagulation (DIC) is a life-threatening condition with high mortality, necessitating timely and accurate diagnosis for effective management. However, current diagnostic systems can not recognize DIC at its reversible phase, causing suboptimal treatment outcomes. One reason is that most venous thrombosis cases are asymptomatic. Moreover, the focus on abnormalities in coagulation consumption often fails to identify DIC until in a later and irreversible phase. Consequently, the current diagnostic criteria for DIC lacks earlier laboratory indicators. Therefore, our objective was to evaluate the diagnostic potential of selected hemostatic biomarkers (thrombin-antithrombin complex (TAT), soluble thrombomodulin (sTM), tissue plasminogen activator inhibitor complex (tPAI-C), α 2-plasmin inhibitor plasmin complex (PIC) and anti-thrombin III (ATIII)) in assessing DIC before reaching its irreversible phase. Methods We included 451 patients from intensive care unit who met the following criteria:≥18 years old, non-perinatal period, and a hospitalization length of≥3 days, excluding those with primary hematologic diseases, decompensated liver cirrhosis or chemotherapy history. In total, 101, 57, and 293 patients were diagnosed with overt-DIC (decompensated DIC), pre-DIC (compensated DIC), and non-DIC, respectively. The DIC scores were calculated in accordance with the diagnostic criteria outlined by the International Society on Thrombosis and Haemostasis (ISTH). Day 0 was defined as the day on which hemostatic biomarkers were detected. Global parameters including prothrombin time (PT), fibrinogen (FIB), fibrinogen degradation product (FDP), d-dimer, and platelet count were collected on day 0, 1, 3, 5, and 7. The spearman correlation analysis was used to analyze the linear relation. Binary logistic regression analysis and receiver operating characteristic curves were used to calculate the area under the receiver operating characteristic curve (AUC). The cutoff value maximizes the sum of the sensitivity and specificity. P&amp;lt;0.05 was considered statistically significant. Results Correlation analysis revealed significant linear correlations between TAT, ATIII, and the global parameters relevant to DIC (pre-DIC and overt-DIC). Specifically, TAT exhibited positive correlation with d-dimer and FDP, while ATIII was correlated with PT, FIB, and platelet count. Of note, TAT/ATIII ratio on day 0 exhibited strong associations not only with fibrinolytic markers but also with coagulation parameters within a week, indicating its potential to be a valuable diagnostic and predictive tool for DIC assessment. Comparative analysis demonstrated elevated TAT and decreased ATIII levels in DIC group. Remarkably, the TAT/ATIII ratio demonstrated superior diagnostic performance compared to individual biomarkers. Among individual biomarkers, TAT/ATIII ratio had the highest AUC of 0.818 with a cutoff value of 22.1, followed by ATIII (AUC=0.752) and TAT (AUC=0.749). Moreover, when a combination of TAT and ATIII was applied, the AUC increased to 0.847 higher than TAT/ATIII ratio's, improving the diagnostic accuracy for DIC. TAT and ATIII in pre-DIC group were consistent with those observed in DIC group above: elevated TAT levels, decreased ATIII activity, TAT/ATIII ratio with superior diagnostic performance. Among individual biomarkers, TAT/ATIII ratio had the highest AUC 0.771 with a cutoff value of 22.1 that maximized the sum of sensitivity (55%) and specificity (89%), followed by TAT (AUC=0.73) and ATIII (AUC=0.707). The AUC of TAT combination with ATIII was 0.796, higher than AUC 0.771 of TAT/ATIII ratio, suggesting that TAT and ATIII may also identify the pre-DIC status and predict overt-DIC. Conclusion This study underscores the remarkable potential of TAT, ATIII, and the TAT/ATIII ratio in predicting DIC with accuracies of 73%, 71%, and 77%, respectively. Moreover, for patients with an ISTH-DIC score of &amp;lt; 5, the presence of following conditions-TAT level ≥10.8 ng/mL, ATIII activity ≤0.58, or TAT/ATIII ratio ≥22.1-indicates a likelihood of developing into irreversible DIC within 7 days. Integrating TAT, ATIII, and the TAT/ATIII ratio into the diagnostic process holds the potential to expedite clinical interventions during the pre-DIC state and enhance outcomes for DIC patients, further covering the shortage of current ISTH criteria.

Establishment and validation of a risk prediction model for disseminated intravascular coagulation patients with electrical burns

Establishment and validation of a risk prediction model for disseminated intravascular coagulation patients with electrical burns

Surgery-related disseminated intravascular coagulation predicts postoperative complications

PurposeThe rate of postoperative morbidity, including infectious complications, is still high after major hepatobiliary pancreatic (HBP) surgery. Although surgery-related disseminated intravascular coagulation (DIC) occurs in some cases, its significance has not been elucidated in HBP surgery. This study aimed to evaluate the influence of surgery-related DIC on the complication severity after HBP surgery.MethodsWe analyzed the records of 100 patients with hepatectomy in two or more segments, hepatectomy with biliary tract reconstruction, and pancreaticoduodenectomy. The baseline characteristics and complications were compared between patients with and without surgery-related DIC on postoperative day 1 (POD1) after HBP surgery between 2010 and 2018. Complication severity was assessed using the Comprehensive Complication Index (CCI).ResultsThe DIC group (surgery-related DIC on POD1) had predictive factors, such as larger bleeding volume and higher liver enzyme levels. The DIC group exhibited significantly elevated rates of surgical site infection, sepsis, prolonged intensive care unit stay, more frequent blood transfusions, and higher CCI. Furthermore, compared with and without adjustment of DIC, odds ratio (OR) of AST level and operation time for the risk of high CCI decreased (OR of AST level: 1.25 to 1.19 and OR of operation time: 1.30 to 1.23) and the significant differences had vanished.ConclusionsSurgery-related DIC on POD1 could be a partial mediator between AST level, operation time and higher CCI. The prevention or proper management of surgery-related DIC on POD1 can be an important target to reduce the severity of postoperative complications.

Predictive value of the maximum aggregation rate of platelet for septic shock and septic shock with disseminated intravascular coagulation

To investigate the predictive value of the maximum aggregation rate (MAR) of platelet for septic shock and septic shock with disseminated intravascular coagulation (DIC). A retrospective case-control study enrolled patients with sepsis admitted to department of critical care medicine of the First Affiliated Hospital of Zhengzhou University from January 2021 to November 2022. The basic data, dynamic platelet aggregation rate, blood routine, inflammation indicators, sequential organ failure assessment (SOFA) and other clinical indicators within 24 hours after admission were collected. Septic patients were divided into the shock group and the non-shock group according to the presence of septic shock; then refer to the International Society on Thrombosis and Hemostasis (ISTH) standard, patients with septic shock were divided into the shock DIC group and the shock non-DIC group according to the presence of dominant DIC. Compared the differences in platelet aggregation function between these groups, and the receiver operator characteristic curve (ROC curve) was drawn to evaluate the predictive value of the MAR for septic shock and septic shock with DIC. Spearman correlation analysis was used to analyze the correlation of MAR with inflammation indicators and the severity of illness in patients with sepsis. A total of 153 sepsis patients were included and 61 with septic shock (including 17 with dominant DIC and 44 without dominant DIC). Compared with the non-shock group, the level of procalcitonin (PCT), C-reactive protein (CRP), and SOFA score were significantly higher in the shock group [PCT (mg/L): 6.90 (2.50, 23.50) vs. 0.87 (0.26, 5.75), CRP (mg/L): 156.48 (67.11, 230.84) vs. 90.39 (46.43, 182.76), SOFA score: 11.00 (8.00, 14.00) vs. 5.00 (3.00, 8.00), all P < 0.05]. The platelet count (PLT) and the MAR induced by adenosine diphosphate (ADP), adrenaline (A), collagen (COL), and arachidonic acid (AA; ADP-MAR, A-MAR, COL-MAR, AA-MAR) in the shock group were significantly decreased [PLT (×109/L): 101.00 (49.00, 163.50) vs. 175.50 (108.25, 254.50), ADP-MAR: 28.50% (22.00%, 38.05%) vs. 45.90% (33.98%, 60.28%), A-MAR: 38.90% (30.00%, 55.40%) vs. 65.15% (54.38%, 72.53%), COL-MAR: 27.90% (20.85%, 36.55%) vs. 42.95% (33.73%, 54.08%), AA-MAR: 24.70% (16.40%, 34.20%) vs. 46.55% (28.33%, 59.20%), all P < 0.05]. Subgroup analysis revealed that, compared with the shock non-DIC group, the SOFA scores were significantly higher in patients in the shock DIC group (13.29±5.23 vs. 10.39±3.58, P < 0.05), the PLT and COL-MAR in the shock DIC group were significantly reduced [PLT (×109/L): 36.00 (22.00, 67.50) vs. 115.50 (84.25, 203.75), COL-MAR: 21.50% (17.85%, 32.60%) vs. 30.95% (22.98%, 38.53%), all P < 0.05]. ROC curve analysis showed that A-MAR had a higher predictive value for septic shock, and the area under the ROC curve (AUC) was 0.814 [95% confidence interval (95%CI) was 0.742-0.886, P = 0.000]. When the optimal cut-off value was 51.35%, the sensitivity was 68.9%, the specificity was 82.6%, the positive predictive value was 0.724 and the negative predictive value was 0.800. COL-MAR had some predictive value for septic shock with DIC, and the AUC was 0.668 (95%CI was 0.513-0.823, P = 0.044). When the optimal cut-off value was 21.90%, the sensitivity was 52.9%, the specificity was 79.5%, the positive predictive value was 0.500, and the negative predictive value was 0.813. Spearman correlation analysis showed that the MAR induced by each inducer was negatively correlated with inflammatory indicators and SOFA scores in sepsis patients, with A-MAR showing the strongest correlation with SOFA score (r = -0.327, P = 0.000). MAR, an indicator of platelet aggregation function, shows predictive value for septic shock and septic shock with DIC, and it could be used to for evaluating the severity of patients with sepsis. In addition, tt also can be used as a monitoring index to predict the changes of sepsis patients and to guide the treatment.

Distinguishing immune-mediated thrombotic thrombocytopenic purpura from septic disseminated intravascular coagulation using plasma levels of haptoglobin and factor XIII activity

BackgroundBoth immune-mediated thrombotic thrombocytopenic purpura (iTTP) and septic disseminated intravascular coagulation (DIC) are life-threatening disorders developed by platelet-consuming microvascular thrombi and necessitate immediate therapeutic interventions. Although severe deficiencies of plasma haptoglobin in iTTP and factor XIII (FXIII) activity in septic DIC have been reported, few studies have focused on the possibility of using these markers to distinguish between iTTP and septic DIC. ObjectivesWe investigated whether the plasma levels of haptoglobin and FXIII activity could be helpful for differential diagnosis. MethodsThirty-five patients with iTTP and 30 with septic DIC were enrolled in the study. Patient characteristics, coagulation, and fibrinolytic markers were collected from the clinical data. Plasma haptoglobin and FXIII activities were measured using chromogenic Enzyme-Linked Immuno Sorbent Assay and an automated instrument, respectively. ResultsThe median plasma haptoglobin level was 0.39 mg/dL and 54.20 mg/dL in the iTTP and septic DIC groups, respectively. The median plasma FXIII activities were 91.3% and 36.3% in the iTTP and septic DIC groups, respectively. In the receiver operating characteristic curve analysis, the cutoff level of plasma haptoglobin was 2.868 mg/dL and the area under the curve was 0.832. The cutoff level for plasma FXIII activity and the area under the curve were 76.0% and 0.931, respectively. The thrombotic thrombocytopenic purpura (TTP)/DIC index was defined by FXIII activity (percentage) and haptoglobin (milligrams per decilitre). Laboratory TTP was defined as an index ≥60 and laboratory DIC <60. The sensitivity and specificity of the TTP/DIC index were 94.3% and 86.7%, respectively. ConclusionThe TTP/DIC index, composed of plasma levels of haptoglobin and FXIII activity, is useful in differentiating iTTP from septic DIC.

Sepsis-Associated DIC with Decreased Levels of Antithrombin and Fibrinogen is the Target for Combination Therapy with Thrombomodulin Alfa and Antithrombin.

Background Disseminated intravascular coagulation (DIC) is not a homogeneous condition, but rather includes heterogeneous conditions, and its pathophysiology and outcome vary considerably depending on the background. Although anticoagulant therapy is expected to be of benefit in the treatment of DIC, previous studies have suggested that the benefits are limited only to a specific subtype. Objects The purpose of this study was to identify the group that would benefit from combination therapy using thrombomodulin/antithrombin. Methods The data from 2,839 patients registered in the postmarketing surveillance of thrombomodulin were evaluated. The patients were divided into four groups depending on antithrombin and fibrinogen levels, and the additive effects of antithrombin on thrombomodulin were examined in the groups. Results The DIC score, Sequential Organ Failure Assessment score, and mortality were significantly higher in the DIC group with low-antithrombin/low-fibrinogen than in the DIC groups without either low antithrombin or low fibrinogen. The survival curve was significantly higher in DIC patients with combination therapy than in patients treated with thrombomodulin monotherapy, but this effect was seen only in patients with infection-based DIC. Conclusion DIC patients with low-antithrombin/low-fibrinogen risk poor outcomes, but they can be the target of combination therapy with antithrombin and thrombomodulin as long as the DIC is due to infection.

Differential Diagnosis Distinguishing Immune TTP from Septic DIC Using Plasma Levels of Haptoglobin and Factor XIII Activity

Introduction Differential diagnosis of immune thrombotic thrombocytopenic purpura (iTTP) and septic disseminated intravascular coagulation (DIC) in daily clinical practice is difficult. iTTP is diagnosed by deficiency of ADAMTS13 activity and ADAMTS13 inhibitor positivity. However, it is difficult to rapidly measure ADAMTS13 activity in real-time in clinical practice. Prompt therapeutic interventions are directly dependent on iTTP prognosis. A method for differentiating between these two disorders using common laboratory tests is needed. Plasma haptoglobin levels can indicate hemolysis and are reported to be severely decreased in iTTP. Coagulation factor XIII (FXIII) activity is also severely decreased in septic DIC. To date, no reports have observed haptoglobin in septic DIC or FXIII activity in iTTP. We analyzed the plasma levels of haptoglobin and FXIII activity in patients with iTTP and septic DIC to investigate whether these markers can be used for differential diagnosis. Methods iTTP was defined as <10% normal ADAMTS13 activity, and >0.5 BU/mL ADAMTS13 inhibitor. Septic DIC was defined as meeting both Third International Consensus Definitions for Sepsis and Septic Shock, and ISTH DIC diagnostic criteria. Thirty-five patients with iTTP and 30 with septic DIC were enrolled in this study. Plasma haptoglobin levels were measured using Human Quantikine ELISA Kits (#DPHAGO, R&D Systems, Inc., Minneapolis, USA), which is a highly sensitive method compared to methods used in clinical practice. Values are expressed as medians (first quartile-third quartile). Results As shown in the table, iTTP patients were significantly younger than those with septic DIC. The iTTP group showed significantly lower ADAMTS13 activity, higher ADAMTS13 inhibitor titer, lower hemoglobin level, lower platelet counts, higher LDH level, and lower creatinine level than the septic DIC group. In a comparison of coagulation and fibrinolytic markers, the septic DIC group had significantly higher PT-INR, prolonged APTT, higher FDP and D-dimer levels, and lower AT activity than the iTTP group. The plasma haptoglobin level was 0.39 mg/dL (0.18-0.76 mg/dL) in the iTTP group, and 54.2 mg/dL (0.6-143.9 mg/dL) in the septic DIC group (P < 0.01). FXIII activity was 91.3% (80.4-115.0%) in the iTTP group, and 36.3% (14.7-61.9%) in the septic DIC group (p<0.01). The ROC curve of haptoglobin and FXIII activity in the differential diagnosis of TTP and septic DIC were investigated. The cut-off level of haptoglobin was 2.868 mg/dL, the area under the curve (AUC) was 0.832 (95% CI:0.727-0.938), specificity was 66.7%, and sensitivity was 100%. The cutoff level of FXIII activity was 76.0%, AUC was 0.931 (95%CI:0.873-0.989), specificity was 77.1%, and sensitivity was 93.3%. We developed a scoring system to differentiate iTTP from septic DIC using a combination of FXIII activity and haptoglobin; TTP/DIC index = plasma FXIII activity (%) - plasma haptoglobin (mg/dL). Laboratory TTP was defined when the index was ≥60, and laboratory DIC was defined when the index was <60. The AUC for the combination of FXIII activity and haptoglobin was 0.968 (95% CI: 0.9354-1). The accuracy of iTTP diagnosis in laboratory TTP was 89.2% (33/37), and the accuracy of septic DIC diagnosis in laboratory DIC was 92.9% (26/28). Conclusions A comparison of iTTP and septic DIC showed significant differences in haptoglobin and FXIII activity levels. A combination of haptoglobin and FXIII activity was considered helpful in differentiating iTTP from septic DIC. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Application of the International Society on Thrombosis and Haemostasis Scoring System in Evaluation of Disseminated Intravascular Coagulation in Patients with Acute Leukemias.

Background Coagulation abnormalities are common in acute leukemia (AL) and disseminated intravascular coagulation (DIC) frequently complicates the onset of AL. Aim To determine the prevalence of overt DIC in AL using the International Society on Thrombosis and Haemostasis (ISTH) scoring system. Materials and Methods This prospective observational study was performed on 57 newly diagnosed or relapsed cases of AL. Detailed clinical history and coagulation profile of the patients were evaluated. Diagnosis of overt and nonovert DIC was established using the ISTH scoring system and results tabulated. Observations A total of 57 patients with AL participated in the study, including 31 (54.39%) patients with acute lymphoblastic leukemia (ALL) and 26 (45.61%) with acute myeloid leukemia (AML). In total, 18 of 57 patients (31.58%) with AL fulfilled the criteria of overt DIC according to the ISTH scoring system, including 10 (32.25%) patients with ALL and 8 (30.76%) patients with AML. The highest prevalence of DIC was seen in the M3 subtype among AML and the L1 subtype among ALL, respectively. The mean ISTH score in patients of overt DIC in ALL and AML patients was 5.1 and 5, respectively. Abnormalities in platelet count and D-dimer levels were the most useful parameters in diagnosing overt DIC and the difference between overt DIC and nonovert DIC groups was highly significant. Conclusions Overt DIC was observed in approximately one-third of patients with AL. Prevalence of overt DIC was found to be comparable in patients with ALL and AML. Mean platelet count and D-dimer levels were the most useful parameters in detecting overt DIC.

Pathophysiology of Coagulopathy Induced by Traumatic Brain Injury Is Identical to That of Disseminated Intravascular Coagulation With Hyperfibrinolysis.

Background: Traumatic brain injury (TBI)-associated coagulopathy is a widely recognized risk factor for secondary brain damage and contributes to poor clinical outcomes. Various theories, including disseminated intravascular coagulation (DIC), have been proposed regarding its pathomechanisms; no consensus has been reached thus far. This study aimed to elucidate the pathophysiology of TBI-induced coagulopathy by comparing coagulofibrinolytic changes in isolated TBI (iTBI) to those in non-TBI, to determine the associated factors, and identify the clinical significance of DIC diagnosis in patients with iTBI.Methods: This secondary multicenter, prospective study assessed patients with severe trauma. iTBI was defined as Abbreviated Injury Scale (AIS) scores ≥4 in the head and neck, and ≤2 in other body parts. Non-TBI was defined as AIS scores ≥4 in single body parts other than the head and neck, and the absence of AIS scores ≥3 in any other trauma-affected parts. Specific biomarkers for thrombin and plasmin generation, anticoagulation, and fibrinolysis inhibition were measured at the presentation to the emergency department (0 h) and 3 h after arrival.Results: We analyzed 34 iTBI and 40 non-TBI patients. Baseline characteristics, transfusion requirements and in-hospital mortality did not significantly differ between groups. The changes in coagulation/fibrinolysis-related biomarkers were similar. Lactate levels in the iTBI group positively correlated with DIC scores (rho = −0.441, p = 0.017), but not with blood pressure (rho = −0.098, p = 0.614). Multiple logistic regression analyses revealed that the injury severity score was an independent predictor of DIC development in patients with iTBI (odds ratio = 1.237, p = 0.018). Patients with iTBI were further subdivided into two groups: DIC (n = 15) and non-DIC (n = 19) groups. Marked thrombin and plasmin generation were observed in all patients with iTBI, especially those with DIC. Patients with iTBI and DIC had higher requirements for massive transfusion and emergency surgery, and higher in-hospital mortality than those without DIC. Furthermore, DIC development significantly correlated with poor hospital survival; DIC scores at 0 h were predictive of in-hospital mortality.Conclusions: Coagulofibrinolytic changes in iTBI and non-TBI patients were identical, and consistent with the pathophysiology of DIC. DIC diagnosis in the early phase of TBI is key in predicting the outcomes of severe TBI.

Relationship between serum zinc level and sepsis-induced coagulopathy.

We investigated whether a decrease in the serum zinc level (SZL) among patients with sepsis admitted to the intensive care unit (ICU) was related to sepsis-induced coagulopathy. All patients (≥20 years) with a diagnosis of sepsis defined by Sepsis-3 criteria, presenting to the ICU between June 2016 and July 2017, were enrolled. Demographic characteristics and the Sequential Organ Failure Assessment (SOFA) and Japanese Association of Acute Medicine (JAAM) disseminated intravascular coagulation (DIC) scores were recorded. Blood samples were collected upon admission and analyzed for SZL. One hundred patients with sepsis (median age, 70 years) were enrolled. Patients with SOFA scores ≥8 had a significantly lower SZL compared to those with SOFA scores <8 (p < 0.001). The SZL in the DIC group (JAAM DIC score ≥4) was significantly lower than that in the non-DIC group (JAAM DIC score <4) (p < 0.001). Analysis of receiver operating characteristic (ROC) curves for prediction of sepsis-induced DIC based on SZL in patients with sepsis showed a cut-off value of 25 µg/dL for zinc level and a sensitivity of 63% and a specificity of 72% with AUC of 0.7 (p = 0.0065). We observed that SZL reflects organ failure, particularly coagulopathy, in patients with sepsis.

Which Septic Shock Patients With Non-Overt DIC Progress to DIC After Admission? Point-of-Care Thromboelastography Testing.

Disseminated intravascular coagulation (DIC) is a life-threatening complication of septic shock; however, risk factors for its development after admission are unknown. Thromboelastography (TEG) can reflect coagulation disturbances in early non-overt DIC that are not detected by standard coagulation tests. This study investigated the risk factors including TEG findings as early predictors for DIC development after admission in septic shock patients with non-overt DIC. This retrospective observation study included 295 consecutive septic shock patients with non-overt DIC at admission between January 2016 and December 2019. DIC was defined as an International Society on Thrombosis and Hemostasis (ISTH) score ≥ 5. The primary outcome was non-overt DIC at admission that met the ISTH DIC criteria within 3 days after admission. Of the 295 patients with non-overt DIC, 89 (30.2%) developed DIC after admission. The DIC group showed a higher ISTH score and 28-day mortality rate than the non-DIC group (2 vs. 3, P < 0.001; 13.6% vs. 27.0%, P = 0.008, respectively). The DIC rate increased with the ISTH score (7.7%, 13.3%, 15.8%, 36.5%, and 61.4% for scores of 0, 1, 2, 3, and 4, respectively). Among TEG values, the maximum amplitude (MA) was higher in the non-DIC group (P < 0.001). On multivariate analysis, an MA < 64 mm was independently associated with DIC development (odds ratio, 2.311; 95% confidence interval, 1.298-4.115). DIC more often developed among those with admission ISTH scores ≥ 3 and was associated with higher mortality rates. An MA < 64 mm was independently associated with DIC development in septic shock patients.

Evaluation the Value of TAT, PIC, tPAIC, TM in Diagnosing Disseminated Intravascular Coagulation in Chinese population: a Multi-Center Prospective Observational Study

Objective: Accurate and early diagnosis are important in the management of disseminated intravascular coagulation (DIC). New specific coagulation markers have always been explored. In this study, we employed new automation technology to detect plasma biomarkers, including Thrombin-Antithrombin Complex (TAT), α2-Plasmininhibitor-Plasmin Complex(PIC), thrombomoduline (TM), tissue plasminogen activator-inhibitor Complex (tPAIC), and evaluated their diagnostic performance for DIC in Chinese population.Method: A prospective observational study was conducted in 9 hospitals located across the entire China. 406 patients suspected DIC and 137 normal people were included. These four molecular markers were measured by qualitative chemiluminescence enzyme immunoassay performed on automated analyzers HISCL. All patients suspected DIC were followed for development of overt-DIC in 7 days, and for mortality in 28 days.Results: The plasm level of TAT, PIC, tPAIC and TM in normal Chinese people were 1.1 (0.7-1.6), 0.44 (0.37-0.56), 7.2(5.1-9.3) and 8.6 (7.3-9.9). According to the ISTH scoring system, 146 patients were diagnosed as overt-DIC, and 37 were diagnosed as pre-DIC. All four biomarkers were significantly higher in DIC group than non-overt DIC group, and tPAIC and TM were significantly higher in pre-DIC group than non-overt DIC group (Table 1). Besides, these molecular markers were different among various underlying diseases(Fig.1). As shown in the ROC assay, the efficiency of TAT, PIC, tPAIC and TM discriminated well between overt- DIC with pre-DIC and non-overt DIC (AUROC, 0.64 (95% CI, 0.58 to 0.69); 0.63 (0.57 to 0.68); 0.63 (0.58 to 0.69);0.73 (0.68 to 0.78), respectively)(Table 2). In the combination assay, the AUROC rose up to 0.955 (0.94 to 0.97) when in addition with global coagulation tests (Fig.2). Moreover, the ISTH DIC scores showed significant correlation with these molecular markers' levels. The mortality of DIC, pre-DIC and non-DIC was 33.56%, 51.35% and 8.97%, respectively. Among the significant diagnostic markers for DIC, TAT, tPAIC and TM were also good predictors of 28-day mortality (AUROC, 0.65, 0,76 and 0.76, respectively), high levels of them were associated with poor outcome(Fig.3).Conclusion: These four biomarkers have good diagnostic performance and prognostic value in DIC patients with different underlying diseases. They can also be applied in classification and stages of DIC. Moreover, combination of four makers demonstrate better behavior than single one. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Hypocoagulable Tendency on Thromboelastometry Associated With Severity and Anticoagulation Timing in Pediatric Septic Shock: A Prospective Observational Study.

Objective: To identify whether coagulation profiles using thromboelastometry are associated with outcomes in pediatric septic shock. The primary outcomes were the development of disseminated intravascular coagulation (DIC) and the severity of the pediatric intensive care unit (PICU) existing scoring systems, while the secondary outcome was hospital mortality. This study aimed to contribute to current findings of the limitations of conventional tests in determining the optimal timing of anticoagulation in sepsis.Design: A prospective, observational study conducted between August 2019 and August 2020.Setting: PICU at a pediatric tertiary hospital in Hanoi, Vietnam.Patients: Fifty-five pediatric patients who met the septic shock criteria were enrolled.Measurements and Main Results: Fifty-five patients with septic shock were recruited. At the time of diagnosis, thromboelastometry revealed normocoagulability, hypercoagulability, and hypocoagulability in 29, 29, and 42% of the patients, respectively (p > 0.05); however, most patients in the overt DIC and non-survival groups progressed to hypocoagulability (82 and 64%, respectively). The overt DIC, PELOD-2 > 8, PRISM-III > 11, and non-survival group had a significant hypocoagulable tendency according to thromboelastometry parameters [prolonged clotting time (CT) and clot formation time (CFT); and reduced α-angle (α), maximum clot firmness (MCF), thrombodynamic potential index (TPI)] compared to the non-overt DIC, PELOD-2 ≤ 8, PRISM-III score ≤ 11 and survival group (p < 0.05). Conventional parameters between the normocoagulable and hypercoagulable groups were not different (p > 0.05). Hypocoagulability was characterized by lower platelet count and fibrinogen level, higher prolonged prothrombin time (PT), international normalized ratio (INR), and activated partial thromboplastin time (APTT), and higher D-dimer level than in hypercoagulability (p < 0.05). Hypocoagulable tendency on thromboelastometry had a higher hazard at a PT > 16.1 s [area under the curve (AUC) = 0.747, odds ratio (OR) = 10.5, p = 0.002], INR > 1.4 (AUC = 0.754, OR = 6.9, p = 0.001), fibrinogen <3.3 g/L (AUC = 0.728, OR = 9.9, p = 0.004), and D-dimer > 3,863 ng/mL (AUC = 0.728, OR = 6.7, p = 0.004).Conclusions: Hypocoagulable tendency using thromboelastometry is associated with the severity of septic shock. Conventional coagulation tests may fail to detect hypercoagulability, which is crucial in determining anticoagulation timing.

English

BACKGROUND Obstetric practitioners routinely deal with antenatal patients who have high risk of developing established coagulopathy, which leads to a very high incidence of maternal morbidity and mortality. We wanted to assess the role of blood components in preventing disseminated intravascular coagulation (DIC) in highrisk patients and determine the amount of blood components required along with the rate of improvement in the DIC score, during treatment of high-risk obstetric patients of DIC and in patients with established DIC. METHODS This is an interventional study. 274 obstetric patients who were at high risk for developing DIC and / or with established DIC admitted during the 20 months study duration were included in the study. Patients were categorized in to three groups based on the DIC score according to ISTH scoring system in to non-overt and overt DIC groups. Those with DIC score &lt; 5 were grouped as IA and IB randomly and those with DIC score &gt; / = 5 were grouped as II. Software used was ANOVA using variance ratio F test for testing the significance between groups and chisquare test was used to find out the association between the groups or parameter. RESULTS Prophylactic transfusion of blood components showed faster rate of improvement than control group. Average consumption of blood components was more in patients of established coagulopathy as compared to non-overt group. CONCLUSIONS Transfusion of blood components can prevent overt DIC in high-risk patients. KEYWORDS DIC - Disseminated Intravascular Coagulation, PPH - Post Partum Haemorrhage, Coagulopathy, Component Therapy

Effect of disseminated intravascular coagulation on donation after citizens' death donor kidneys.

BackgroundTo investigate the effect of disseminated intravascular coagulation (DIC) on donor kidney in donation after citizens’ death (DCD) donors.MethodsThe clinical and laboratory data of 159 DCD donors obtained by our center in 2018 were retrospectively analyzed. The DIC diagnosis was performed according to the Chinese DIC scoring system (CDSS). The donors were divided into two groups: DIC (+) and DIC (−). The difference between kidney rejection rate and zero puncture glomerular microthrombus formation rate were compared.ResultsAmong the 159 DCD donors, 11 were discarded (accounting for 6.91%). The reasons for the discarded cases included 5 cases (3.14%) for moderate and severe glomerular microthrombus formation in the renal zero puncture pathology; 2 cases (1.26%) for glomerular sclerosis ratio over 50%; 2 cases (1.26%) for long-term low blood pressure before pregnancy and significantly increased serum creatinine level and no urine; 1 case (0.73%) for kidney stones and stagnant water; 1 case (0.63%) for malignant tumor. The donor rejection rate of the DIC (+) group was higher than that of the DIC (−) group, and the difference was statistically significant (P<0.05). Among all donors, 10 cases (6.29%) were found to have glomerular microthrombus at zero puncture, and the microthrombotic rate in the DIC (+) group was significantly higher than that in the DIC (−) group (P<0.05). Of the 10 microthrombotic donors, 5 donors with severe glomerular microthrombus were discarded.ConclusionsDonor-induced DIC can easily cause renal glomerular microthrombus formation, and the donor kidney rejection rate has increased.

Role of Thromboelastography as an Early Predictor of Disseminated Intravascular Coagulation in Patients with Septic Shock.

(1) Background: The currently proposed criteria for diagnosing overt disseminated intravascular coagulation (DIC) are not suitable for early detection of DIC. Thromboelastography (TEG) rapidly provides a comprehensive assessment of the entire coagulation process and is helpful as a guide for correcting consumptive coagulopathy in sepsis-induced DIC. This study aimed to investigate the role of TEG in the prediction of DIC in patients with septic shock. (2) Methods: TEG was conducted prospectively in 1294 patients with septic shock at the emergency department (ED) between January 2016 and December 2019. After exclusion of 405 patients with “do not attempt resuscitation” orders, those refusing enrollment, and those developing septic shock after ED presentation, 889 patients were included. DIC was defined as an International Society on Thrombosis and Hemostasis score ≥ 5 points within 24 h. (3) Results: Of the 889 patients with septic shock (mean age 65.6 ± 12.7 years, 58.6% male), 158 (17.8%) developed DIC. TEG values, except lysis after 30 min, were significantly different between the DIC and non-DIC groups. Among the TEG values, the maximal amplitude (MA) had the highest discriminating power for DIC, with an area under the curve of 0.814. An MA < 60 indicated DIC with 79% sensitivity, 73% specificity, and 94% negative predictive value. Based on multivariable analysis, MA < 60 was an independent predictor of DIC (odds ratio 5.616 (95% confidence interval: 3.213–9.818)). (4) Conclusions: In patients with septic shock, the MA value in TEG could be a valuable tool for early prediction of DIC.

Diagnostic Value of Thromboelastography for Acute Disseminated Intravascular Coagulation

To investigate the diagnostic value of thromboelastography(TEG) for acute disseminated intravascular coagulation(DIC). The clinical data and data of blood routine indexes, blood coagulation indexes and TEG indexes of acute 155 DIC patients were collected and analyzed retrospectively. The CDSS scores of DIC and non-DIC groups were 9.2±1.4 and 4.2±1.1 respectively, and the CDSS scores of DIC group was significantly higher than those in non-DIC group(P＜0.05). The PLT level in DIC group was significantly lower than that in non-DIC group(P＜0.05), the PT, APTT, INT, DD and FIB levels in DIC group were significantly higher than those in non-DIC group(P＜0.05). The R time, K time and LY30 in DIC group were significantly higher than those in non-DIC group(P＜0.05), and the α and MA in DIC group were significantly lower than those in non-DIC group(P＜0.05). ROC curve analysis showed that the best cutoff value of R time, K time, α, MA and LY30 were 8.4 min, 6.2 min, 52.5°, 43.2 mm and 6.7% respectively. The AUC of total scores≥1, ≥2, ≥3 and ≥4 were 0.552, 0.650, 0.687 and 0.613 respectively. The TEG possesses the certain value in the diagnosing of DIC.